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1. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.

Author

Chen, Yuyang, Dawes, Ruebena, Kim, Hyung, Ljungdahl, Alicia, Stenton, Sarah, Walker, Susan, Lord, Jenny, Lemire, Gabrielle, Martin-Geary, Alexandra, Ganesh, Vijay, Ma, Jialan, Ellingford, Jamie, Delage, Erwan, DSouza, Elston, Dong, Shan, Adams, David, Allan, Kirsten, Bakshi, Madhura, Baldwin, Erin, Berger, Seth, Bernstein, Jonathan, Bhatnagar, Ishita, Blair, Ed, Brown, Natasha, Burrage, Lindsay, Chapman, Kimberly, Coman, David, Compton, Alison, Cunningham, Chloe, DSouza, Precilla, Danecek, Petr, Délot, Emmanuèle, Dias, Kerith-Rae, Elias, Ellen, Elmslie, Frances, Evans, Care-Anne, Ewans, Lisa, Ezell, Kimberly, Fraser, Jamie, Gallacher, Lyndon, Genetti, Casie, Goriely, Anne, Grant, Christina, Haack, Tobias, Higgs, Jenny, Hinch, Anjali, Hurles, Matthew, Kuechler, Alma, Lachlan, Katherine, Lalani, Seema, Lecoquierre, François, Leitão, Elsa, Fevre, Anna, Leventer, Richard, Liebelt, Jan, Lindsay, Sarah, Lockhart, Paul, Ma, Alan, Macnamara, Ellen, Mansour, Sahar, Maurer, Taylor, Mendez, Hector, Metcalfe, Kay, Montgomery, Stephen, Moosajee, Mariya, Nassogne, Marie-Cécile, Neumann, Serena, ODonoghue, Michael, OLeary, Melanie, Palmer, Elizabeth, Pattani, Nikhil, Phillips, John, Pitsava, Georgia, Pysar, Ryan, Rehm, Heidi, Reuter, Chloe, Revencu, Nicole, Riess, Angelika, Rius, Rocio, Rodan, Lance, Roscioli, Tony, Rosenfeld, Jill, Sachdev, Rani, Shaw-Smith, Charles, Simons, Cas, Sisodiya, Sanjay, Snell, Penny, St Clair, Laura, Stark, Zornitza, Stewart, Helen, Tan, Tiong, Tan, Natalie, Temple, Suzanna, Thorburn, David, Tifft, Cynthia, Uebergang, Eloise, VanNoy, Grace, Vasudevan, Pradeep, Vilain, Eric, and Viskochil, David

Subjects
Humans, RNA, Small Nuclear, Neurodevelopmental Disorders, Female, Male, Brain, Heterozygote, Alleles, Syndrome, Spliceosomes, Animals
Abstract

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5 splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

Published
2024

2. Using Smartphone Sensors for Ataxia Trials: Consensus Guidance by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

Author

Németh, Andrea, Antoniades, Chrystalina, Dukart, Juergen, Minnerop, Martina, Rentz, Clara, Schuman, Bart-Jan, van de Warrenburg, Bart, Willemse, Ilse, Bertini, Enrico, Gupta, Anoopum, de Mello Monteiro, Carlos, Almoajil, Hajar, Quinn, Lori, Horak, Fay, Ilg, Winfried, Traschütz, Andreas, Vogel, Adam, Dawes, Helen, and Perlman, Susan

Subjects
Ataxia, Digital motor performance outcome measures, Internal smartphone Sensors, Humans, Smartphone, Consensus, Delphi Technique, Ataxia, Biomarkers, Clinical Trials as Topic
Abstract

Smartphone sensors are used increasingly in the assessment of ataxias. To date, there is no specific consensus guidance regarding a priority set of smartphone sensor measurements, or standard assessment criteria that are appropriate for clinical trials. As part of the Ataxia Global Initiative Digital-Motor Biomarkers Working Group (AGI WG4), aimed at evaluating key ataxia clinical domains (gait/posture, upper limb, speech and oculomotor assessments), we provide consensus guidance for use of internal smartphone sensors to assess key domains. Guidance was developed by means of a literature review and a two stage Delphi study conducted by an Expert panel, which surveyed members of AGI WG4, representing clinical, research, industry and patient-led experts, and consensus meetings by the Expert panel to agree on standard criteria and map current literature to these criteria. Seven publications were identified that investigated ataxias using internal smartphone sensors. The Delphi 1 survey ascertained current practice, and systems in use or under development. Wide variations in smartphones sensor use for assessing ataxia were identified. The Delphi 2 survey identified seven measures that were strongly endorsed as priorities in assessing 3/4 domains, namely gait/posture, upper limb, and speech performance. The Expert panel recommended 15 standard criteria to be fulfilled in studies. Evaluation of current literature revealed that none of the studies met all criteria, with most being early-phase validation studies. Our guidance highlights the importance of consensus, identifies priority measures and standard criteria, and will encourage further research into the use of internal smartphone sensors to measure ataxia digital-motor biomarkers.

Published
2024

3. First-in-human prediction of chronic pain state using intracranial neural biomarkers.

Author

Shirvalkar, Prasad, Prosky, Jordan, Chin, Gregory, Ahmadipour, Parima, Sani, Omid G, Desai, Maansi, Schmitgen, Ashlyn, Dawes, Heather, Shanechi, Maryam M, Starr, Philip A, and Chang, Edward F

Subjects
Gyrus Cinguli, Prefrontal Cortex, Humans, Electrodes, Implanted, Chronic Pain, Neurosciences, Pain Research, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Chronic pain syndromes are often refractory to treatment and cause substantial suffering and disability. Pain severity is often measured through subjective report, while objective biomarkers that may guide diagnosis and treatment are lacking. Also, which brain activity underlies chronic pain on clinically relevant timescales, or how this relates to acute pain, remains unclear. Here four individuals with refractory neuropathic pain were implanted with chronic intracranial electrodes in the anterior cingulate cortex and orbitofrontal cortex (OFC). Participants reported pain metrics coincident with ambulatory, direct neural recordings obtained multiple times daily over months. We successfully predicted intraindividual chronic pain severity scores from neural activity with high sensitivity using machine learning methods. Chronic pain decoding relied on sustained power changes from the OFC, which tended to differ from transient patterns of activity associated with acute, evoked pain states during a task. Thus, intracranial OFC signals can be used to predict spontaneous, chronic pain state in patients.

Published
2023

4. A 1-week sleep and light intervention improves mood in premenstrual dysphoric disorder in association with shifting melatonin offset time earlier

Author

Parry, Barbara L, Meliska, Charles J, Martinez, L Fernando, Lopez, Ana M, Sorenson, Diane L, Dawes, Sharron E, Elliott, Jeffrey A, and Hauger, Richard L

Subjects
Mental Health, Behavioral and Social Science, Clinical Research, Brain Disorders, Depression, Neurosciences, Clinical Trials and Supportive Activities, Sleep Research, Complementary and Integrative Health, Female, Humans, Premenstrual Dysphoric Disorder, Premenstrual Syndrome, Melatonin, Sleep, Luteal Phase, Circadian Rhythm, Premenstrual dysphoric disorder, Wake therapy, Light treatment, Melatonin circadian rhythms, Psychology, Cognitive Sciences, Psychiatry
Abstract

To test the hypothesis that 1 week of combined sleep and light interventions (SALI), which phase-advance (shift earlier) melatonin circadian rhythms, improves mood significantly more than phase-delay (shift later) SALI. After a 2-month diagnostic evaluation for premenstrual dysphoric disorder (PMDD per DSM-5 criteria) in a university clinical research setting, 44 participants enrolled in baseline studies were randomized in the luteal phase at home to (A) a phase-advance intervention (PAI): 1 night of late-night wake therapy (LWT: sleep 9 pm-1 am) followed by 7 days of the morning (AM) bright white light (BWL), or (B) a phase-delay intervention (PDI): 1 night of early-night wake therapy (EWT: sleep 3-7 am) plus 7 days of the evening (PM) BWL. After a month of no intervention, participants underwent the alternate intervention. Outcome measures were mood, the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), and actigraphy (to assess protocol compliance). At baseline, atypical depression correlated positively with phase delay in 6-SMT offset time (r = .456, p = .038). PAI advanced 6-SMT offset from baseline more than PDI (p

Published
2023

5. Complex 33-beam simulated galactic cosmic radiation exposure impacts cognitive function and prefrontal cortex neurotransmitter networks in male mice

Author

Desai, Rajeev I, Kangas, Brian D, Luc, Oanh T, Solakidou, Eleana, Smith, Evan C, Dawes, Monica H, Ma, Xiaoyu, Makriyannis, Alexandros, Chatterjee, Subhamoy, Dayeh, Maher A, Muñoz-Jaramillo, Andrés, Desai, Mihir I, and Limoli, Charles L

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Basic Behavioral and Social Science, Mental Health, Neurosciences, Behavioral and Social Science, 1.2 Psychological and socioeconomic processes, Neurological, Mental health, Mice, Male, Animals, Humans, Space Flight, Astronauts, Radiation Exposure, Cosmic Radiation, Cognition
Abstract

Astronauts will encounter extended exposure to galactic cosmic radiation (GCR) during deep space exploration, which could impair brain function. Here, we report that in male mice, acute or chronic GCR exposure did not modify reward sensitivity but did adversely affect attentional processes and increased reaction times. Potassium (K+)-stimulation in the prefrontal cortex (PFC) elevated dopamine (DA) but abolished temporal DA responsiveness after acute and chronic GCR exposure. Unlike acute GCR, chronic GCR increased levels of all other neurotransmitters, with differences evident between groups after higher K+-stimulation. Correlational and machine learning analysis showed that acute and chronic GCR exposure differentially reorganized the connection strength and causation of DA and other PFC neurotransmitter networks compared to controls which may explain space radiation-induced neurocognitive deficits.

Published
2023

6. Decoding naturalistic affective behaviour from spectro-spatial features in multiday human iEEG

Author

Bijanzadeh, Maryam, Khambhati, Ankit N, Desai, Maansi, Wallace, Deanna L, Shafi, Alia, Dawes, Heather E, Sturm, Virginia E, and Chang, Edward F

Subjects
Biological Psychology, Psychology, Neurosciences, Neurological, Amygdala, Emotions, Gyrus Cinguli, Hippocampus, Humans, Prefrontal Cortex, Biomedical and clinical sciences, Health sciences
Abstract

The neurological basis of affective behaviours in everyday life is not well understood. We obtained continuous intracranial electroencephalography recordings from the human mesolimbic network in 11 participants with epilepsy and hand-annotated spontaneous behaviours from 116 h of multiday video recordings. In individual participants, binary random forest models decoded affective behaviours from neutral behaviours with up to 93% accuracy. Both positive and negative affective behaviours were associated with increased high-frequency and decreased low-frequency activity across the mesolimbic network. The insula, amygdala, hippocampus and anterior cingulate cortex made stronger contributions to affective behaviours than the orbitofrontal cortex, but the insula and anterior cingulate cortex were most critical for differentiating behaviours with observable affect from those without. In a subset of participants (N = 3), multiclass decoders distinguished amongst the positive, negative and neutral behaviours. These results suggest that spectro-spatial features of brain activity in the mesolimbic network are associated with affective behaviours of everyday life.

Published
2022

7. A genome-wide association study of outcome from traumatic brain injury

Author

Kals, Mart, Kunzmann, Kevin, Parodi, Livia, Radmanesh, Farid, Wilson, Lindsay, Izzy, Saef, Anderson, Christopher D, Puccio, Ava M, Okonkwo, David O, Temkin, Nancy, Steyerberg, Ewout W, Stein, Murray B, Manley, Geoff T, Maas, Andrew IR, Richardson, Sylvia, Diaz-Arrastia, Ramon, Palotie, Aarno, Ripatti, Samuli, Rosand, Jonathan, Menon, David K, Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan P, Cooper, Jamie D, Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, DahyotFizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, GuyLoup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L, Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A, Gratz, Johannes, Gravesteijn, Benjamin, and Grossi, Francesca

Subjects
Epidemiology, Health Sciences, Traumatic Head and Spine Injury, Genetics, Physical Injury - Accidents and Adverse Effects, Neurosciences, Brain Disorders, Human Genome, Traumatic Brain Injury (TBI), Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Brain Injuries, Traumatic, Genome-Wide Association Study, Humans, Mannose-Binding Lectin, Prospective Studies, Transcriptome, Traumatic brain injury, Genome-Wide association study, Outcome, Recovery, Consortia, Genetic Associations In Neurotrauma (GAIN) Consortium, Clinical Sciences, Public Health and Health Services, Clinical sciences
Abstract

BackgroundFactors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias.MethodsWe performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography.FindingsThe estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10-8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10-5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10-4).InterpretationWhile multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Published
2022

8. The impact of Mendelian sleep and circadian genetic variants in a population setting

Author

Weedon, Michael N, Jones, Samuel E, Lane, Jacqueline M, Lee, Jiwon, Ollila, Hanna M, Dawes, Amy, Tyrrell, Jess, Beaumont, Robin N, Partonen, Timo, Merikanto, Ilona, Rich, Stephen S, Rotter, Jerome I, Frayling, Timothy M, Rutter, Martin K, Redline, Susan, Sofer, Tamar, Saxena, Richa, and Wood, Andrew R

Subjects
Biological Sciences, Genetics, Sleep Research, Clinical Research, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Circadian Rhythm, Humans, Phenotype, Receptors, G-Protein-Coupled, Sleep, Sleep Wake Disorders, Developmental Biology
Abstract

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10-8; and had a 57-minute earlier midpoint sleep, P = 5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.

Published
2022

9. Closed-loop neuromodulation in an individual with treatment-resistant depression

Author

Scangos, Katherine W, Khambhati, Ankit N, Daly, Patrick M, Makhoul, Ghassan S, Sugrue, Leo P, Zamanian, Hashem, Liu, Tony X, Rao, Vikram R, Sellers, Kristin K, Dawes, Heather E, Starr, Philip A, Krystal, Andrew D, and Chang, Edward F

Subjects
Biomedical and Clinical Sciences, Health Sciences, Major Depressive Disorder, Neurosciences, Mental Health, Brain Disorders, Serious Mental Illness, Rehabilitation, Bioengineering, Mental Illness, Assistive Technology, Depression, Development of treatments and therapeutic interventions, 5.3 Medical devices, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Mental health, Good Health and Well Being, Adult, Biomarkers, Brain, Deep Brain Stimulation, Depressive Disorder, Major, Electric Stimulation, Female, Humans, Severity of Illness Index, Treatment Outcome, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Deep brain stimulation is a promising treatment for neuropsychiatric conditions such as major depression. It could be optimized by identifying neural biomarkers that trigger therapy selectively when symptom severity is elevated. We developed an approach that first used multi-day intracranial electrophysiology and focal electrical stimulation to identify a personalized symptom-specific biomarker and a treatment location where stimulation improved symptoms. We then implanted a chronic deep brain sensing and stimulation device and implemented a biomarker-driven closed-loop therapy in an individual with depression. Closed-loop therapy resulted in a rapid and sustained improvement in depression. Future work is required to determine if the results and approach of this n-of-1 study generalize to a broader population.

Published
2021

10. Long-term wireless streaming of neural recordings for circuit discovery and adaptive stimulation in individuals with Parkinson's disease.

Author

Gilron, Ro'ee, Little, Simon, Perrone, Randy, Wilt, Robert, de Hemptinne, Coralie, Yaroshinsky, Maria S, Racine, Caroline A, Wang, Sarah S, Ostrem, Jill L, Larson, Paul S, Wang, Doris D, Galifianakis, Nick B, Bledsoe, Ian O, San Luciano, Marta, Dawes, Heather E, Worrell, Gregory A, Kremen, Vaclav, Borton, David A, Denison, Timothy, and Starr, Philip A

Subjects
Motor Cortex, Humans, Parkinson Disease, Deep Brain Stimulation, Adaptation, Physiological, Movement, Adult, Middle Aged, Female, Male, Wireless Technology, Neurophysiological Monitoring, Wearable Electronic Devices, Aging, Assistive Technology, Parkinson's Disease, Brain Disorders, Neurodegenerative, Behavioral and Social Science, Rehabilitation, Bioengineering, Neurosciences, Clinical Research, 1.1 Normal biological development and functioning, Underpinning research, Neurological
Abstract

Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson's disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated individual-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation (DBS). This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation.

Published
2021

11. Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury

Author

Yuh, Esther L, Jain, Sonia, Sun, Xiaoying, Pisică, Dana, Harris, Mark H, Taylor, Sabrina R, Markowitz, Amy J, Mukherjee, Pratik, Verheyden, Jan, Giacino, Joseph T, Levin, Harvey S, McCrea, Michael, Stein, Murray B, Temkin, Nancy R, Diaz-Arrastia, Ramon, Robertson, Claudia S, Lingsma, Hester F, Okonkwo, David O, Maas, Andrew IR, Manley, Geoffrey T, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benal, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Castaño‑León, Ana M, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D, Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot‑Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy‑Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L, Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A, Gratz, Johannes, Gravesteijn, Benjamin, and Grossi, Francesca

Subjects
Traumatic Brain Injury (TBI), Traumatic Head and Spine Injury, Biomedical Imaging, Brain Disorders, Neurosciences, Physical Injury - Accidents and Adverse Effects, Clinical Research, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Injuries and accidents, Good Health and Well Being, Adult, Aged, Brain Concussion, Cohort Studies, Female, Humans, Intracranial Hemorrhages, Male, Middle Aged, Prognosis, Recovery of Function, Tomography, X-Ray Computed, TRACK-TBI Investigators for the CENTER-TBI Investigators, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ImportanceA head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.ObjectiveTo identify pathological CT features associated with adverse outcomes after mTBI.Design, setting, and participantsThe longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021.ExposuresAcute nonpenetrating head trauma.Main outcomes and measuresFrequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores

Published
2021

12. Thin-film microfabrication and intraoperative testing ofµECoG and iEEG depth arrays for sense and stimulation.

Author

Chung, Jason, Zhou, Jenny, Triplett, Michael, Dawes, Heather, Haque, Razi, Chang, Edward, and Sellers, Kristin

Subjects
human, iEEG, intracranial stimulation, intraoperative, microfabrication, thin-film arrays, μECoG, Brain-Computer Interfaces, Electrocorticography, Electrodes, Implanted, Humans, Microtechnology, Subdural Space
Abstract

Objective.Intracranial neural recordings and electrical stimulation are tools used in an increasing range of applications, including intraoperative clinical mapping and monitoring, therapeutic neuromodulation, and brain computer interface control and feedback. However, many of these applications suffer from a lack of spatial specificity and localization, both in terms of sensed neural signal and applied stimulation. This stems from limited manufacturing processes of commercial-off-the-shelf (COTS) arrays unable to accommodate increased channel density, higher channel count, and smaller contact size.Approach.Here, we describe a manufacturing and assembly approach using thin-film microfabrication for 32-channel high density subdural micro-electrocorticography (µECoG) surface arrays (contacts 1.2 mm diameter, 2 mm pitch) and intracranial electroencephalography (iEEG) depth arrays (contacts 0.5 mm × 1.5 mm, pitch 0.8 mm × 2.5 mm). Crucially, we tackle the translational hurdle and test these arrays during intraoperative studies conducted in four humans under regulatory approval.Main results.We demonstrate that the higher-density contacts provide additional unique information across the recording span compared to the density of COTS arrays which typically have electrode pitch of 8 mm or greater; 4 mm in case of specially ordered arrays. Our intracranial stimulation study results reveal that refined spatial targeting of stimulation elicits evoked potentials with differing spatial spread.Significance.Thin-film,μECoG and iEEG depth arrays offer a promising substrate for advancing a number of clinical and research applications reliant on high-resolution neural sensing and intracranial stimulation.

Published
2021

13. Effects of body size on estimation of mammalian area requirements

Author

Noonan, Michael J, Fleming, Christen H, Tucker, Marlee A, Kays, Roland, Harrison, Autumn‐Lynn, Crofoot, Margaret C, Abrahms, Briana, Alberts, Susan C, Ali, Abdullahi H, Altmann, Jeanne, Antunes, Pamela Castro, Attias, Nina, Belant, Jerrold L, Beyer, Dean E, Bidner, Laura R, Blaum, Niels, Boone, Randall B, Caillaud, Damien, Paula, Rogerio Cunha, la Torre, J Antonio, Dekker, Jasja, DePerno, Christopher S, Farhadinia, Mohammad, Fennessy, Julian, Fichtel, Claudia, Fischer, Christina, Ford, Adam, Goheen, Jacob R, Havmøller, Rasmus W, Hirsch, Ben T, Hurtado, Cindy, Isbell, Lynne A, Janssen, René, Jeltsch, Florian, Kaczensky, Petra, Kaneko, Yayoi, Kappeler, Peter, Katna, Anjan, Kauffman, Matthew, Koch, Flavia, Kulkarni, Abhijeet, LaPoint, Scott, Leimgruber, Peter, Macdonald, David W, Markham, A Catherine, McMahon, Laura, Mertes, Katherine, Moorman, Christopher E, Morato, Ronaldo G, Moßbrucker, Alexander M, Mourão, Guilherme, O'Connor, David, Oliveira‐Santos, Luiz Gustavo R, Pastorini, Jennifer, Patterson, Bruce D, Rachlow, Janet, Ranglack, Dustin H, Reid, Neil, Scantlebury, David M, Scott, Dawn M, Selva, Nuria, Sergiel, Agnieszka, Songer, Melissa, Songsasen, Nucharin, Stabach, Jared A, Stacy‐Dawes, Jenna, Swingen, Morgan B, Thompson, Jeffrey J, Ullmann, Wiebke, Vanak, Abi Tamim, Thaker, Maria, Wilson, John W, Yamazaki, Koji, Yarnell, Richard W, Zieba, Filip, Zwijacz‐Kozica, Tomasz, Fagan, William F, Mueller, Thomas, and Calabrese, Justin M

Subjects
Generic health relevance, Life on Land, Animals, Body Size, Conservation of Natural Resources, Endangered Species, Homing Behavior, Humans, Mammals, allometry, animal movement, area-based conservation, autocorrelation, home range, kernel density estimation, reserve design, scaling, alometría, autocorrelación, conservación basada en áreas, diseño de reserva, distribución local, escalamiento, estimación de densidad del núcleo, movimiento de mamíferos, 保护区设计, 动物移动, 区域保护, 家域, 异速增长, 标度, 核密度估计, 自相关, Environmental Sciences, Biological Sciences, Agricultural and Veterinary Sciences, Ecology
Abstract

Accurately quantifying species' area requirements is a prerequisite for effective area-based conservation. This typically involves collecting tracking data on species of interest and then conducting home-range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home-range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross-validation to quantify bias in empirical home-range estimates. Area requirements of mammals 1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum.

Published
2020

14. Pilot Study of An Intracranial Electroencephalography Biomarker of Depressive Symptoms in Epilepsy

Author

Scangos, Katherine W, Ahmad, Hasan S, Shafi, Alia, Sellers, Kristin K, Dawes, Heather E, Krystal, Andrew, and Chang, Edward F

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Serious Mental Illness, Brain Disorders, Mental Health, Clinical Research, Epilepsy, Neurosciences, Neurodegenerative, Depression, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Neurological, Adult, Biomarkers, Cerebral Cortex, Drug Resistant Epilepsy, Electrocorticography, Female, Humans, Limbic System, Male, Nerve Net, Pilot Projects, Principal Component Analysis, Biological Markers, Biomarker, ECoG, Treatment Refractory Epilepsy, Cognitive Sciences, Psychiatry, Clinical sciences
Abstract

ObjectivesAdult patients with epilepsy have an increased prevalence of major depressive disorder (MDD). Intracranial EEG (iEEG) captured during extended inpatient monitoring of patients with treatment-resistant epilepsy offers a particularly promising method to study MDD networks in epilepsy.MethodsThe authors used 24 hours of resting-state iEEG to examine the neural activity patterns within corticolimbic structures that reflected the presence of depressive symptoms in 13 adults with medication-refractory epilepsy. Principal component analysis was performed on the z-scored mean relative power in five standard frequency bands averaged across electrodes within a region.ResultsPrincipal component 3 was a statistically significant predictor of the presence of depressive symptoms (R2=0.35, p=0.014). A balanced logistic classifier model using principal component 3 alone correctly classified 78% of patients as belonging to the group with a high burden of depressive symptoms or a control group with minimal depressive symptoms (sensitivity, 75%; specificity, 80%; area under the curve=0.8, leave-one-out cross validation). Classification was dependent on beta power throughout the corticolimbic network and low-frequency cingulate power.ConclusionsThese finding suggest, for the first time, that neural features across circuits involved in epilepsy may distinguish patients who have depressive symptoms from those who do not. Larger studies are required to validate these findings and to assess their diagnostic utility in MDD.

Published
2020

15. Biases in processing of mood-congruent facial expressions in depression

Author

Van Vleet, Thomas, Stark-Inbar, Alit, Merzenich, Michael M, Jordan, Joshua T, Wallace, Deanna L, Lee, Morgan B, Dawes, Heather E, Chang, Edward F, and Nahum, Mor

Subjects
Biological Psychology, Psychology, Clinical Research, Behavioral and Social Science, Brain Disorders, Depression, Mind and Body, Mental Health, Mental health, Adult, Affect, Bias, Cognition, Depressive Disorder, Major, Emotions, Facial Expression, Female, Happiness, Humans, Male, Middle Aged, Reaction Time, Young Adult, Major depressive disorder, MDD, Mood disorders, Affect perception, Processing bias, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

Cognitive models of depression suggest that depressed individuals exhibit a tendency to attribute negative meaning to neutral stimuli, and enhanced processing of mood-congruent stimuli. However, evidence thus far has been inconsistent. In this study, we sought to identify both differential interpretation of neutral information as well as emotion processing biases associated with depression. Fifty adult participants completed standardized mood-related questionnaires, a novel immediate mood scale questionnaire (IMS-12), and a novel task, Emotion Matcher, in which they were required to indicate whether pairs of emotional faces show the same expression or not. We found that overall success rate and reaction time on the Emotion Matcher task did not differ as a function of severity of depression. However, more depressed participants had significantly worse performance when presented with sad-neutral face pairs, as well as increased reaction times to happy-happy pairs. In addition, accuracy of the sad-neutral pairs was found to be significantly associated with depression severity in a regression model. Our study provides partial support for the mood-congruent hypothesis, revealing only a potential bias in interpretation of sad and neutral expressions, but not a general deficit in processing of facial expressions. The potential of such bias in serving as a predictor for depression should be further examined in future studies.

Published
2019

16. Role of Saliva and Salivary Diagnostics in the Advancement of Oral Health

Author

Dawes, C and Wong, DTW

Subjects
Biomedical and Clinical Sciences, Dentistry, Dental/Oral and Craniofacial Disease, Digestive Diseases, Clinical Research, Good Health and Well Being, Biomarkers, Calcium Phosphates, Diagnosis, Oral, History, 20th Century, History, 21st Century, Humans, Oral Health, Periodicals as Topic, Precision Medicine, Saliva, parotid, submandibular/sublingual, exosomics, proteomics, salivaomics, transcriptomics
Abstract

The objective of this article was to provide an account of some of the developments related to saliva over the first 100 years of the Journal of Dental Research and to outline some of the many biomarkers identified in saliva in the last few years. The first section covers findings in salivary physiology, biochemistry, calcium phosphate chemistry related to saliva, microbiology, and the role of saliva in maintaining oral health. The second section highlights salivary diagnostics, salivaomics, and saliva exosomics in the context of the emerging theme of personalized and precision medicine.

Published
2019

17. Dnmt3a is an epigenetic mediator of adipose insulin resistance.

Author

You, Dongjoo, Nilsson, Emma, Tenen, Danielle E, Lyubetskaya, Anna, Lo, James C, Jiang, Rencong, Deng, Jasmine, Dawes, Brian A, Vaag, Allan, Ling, Charlotte, Rosen, Evan D, and Kang, Sona

Subjects
Cells, Cultured, Adipocytes, Animals, Mice, Knockout, Humans, Mice, Insulin Resistance, Gene Expression Profiling, Epigenesis, Genetic, DNA (Cytosine-5-)-Methyltransferases, adipocyte, cell biology, epigenetic, insulin resistance, mouse, Cells, Cultured, Knockout, Epigenesis, Genetic, Genetics, Nutrition, Obesity, Diabetes, 2.1 Biological and endogenous factors, Metabolic and Endocrine, Biochemistry and Cell Biology
Abstract

Insulin resistance results from an intricate interaction between genetic make-up and environment, and thus may be orchestrated by epigenetic mechanisms like DNA methylation. Here, we demonstrate that DNA methyltransferase 3a (Dnmt3a) is both necessary and sufficient to mediate insulin resistance in cultured mouse and human adipocytes. Furthermore, adipose-specific Dnmt3a knock-out mice are protected from diet-induced insulin resistance and glucose intolerance without accompanying changes in adiposity. Unbiased gene profiling studies revealed Fgf21 as a key negatively regulated Dnmt3a target gene in adipocytes with concordant changes in DNA methylation at the Fgf21 promoter region. Consistent with this, Fgf21 can rescue Dnmt3a-mediated insulin resistance, and DNA methylation at the FGF21 locus was elevated in human subjects with diabetes and correlated negatively with expression of FGF21 in human adipose tissue. Taken together, our data demonstrate that adipose Dnmt3a is a novel epigenetic mediator of insulin resistance in vitro and in vivo.

Published
2017

18. The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication

Author

Bharaj, Preeti, Atkins, Colm, Luthra, Priya, Giraldo, Maria Isabel, Dawes, Brian E, Miorin, Lisa, Johnson, Jeffrey R, Krogan, Nevan J, Basler, Christopher F, Freiberg, Alexander N, and Rajsbaum, Ricardo

Subjects
Prevention, Infectious Diseases, Vaccine Related, Immunization, Rare Diseases, Emerging Infectious Diseases, Biodefense, Aetiology, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Animals, Cell Line, Ebolavirus, Host-Pathogen Interactions, Humans, Immunoprecipitation, Mass Spectrometry, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Ubiquitination, Viral Regulatory and Accessory Proteins, Virus Replication, TRIM6, tripartite motif (TRIM) protein, VP35, viral RNA polymerase, Ebola virus, innate immunity, ubiquitination, unanchored ubiquitin, virus-host interactions, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology
Abstract

Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central, and West Africa. The EBOV genome encodes VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type I interferon (IFN-I) system. By using mass spectrometry analysis and coimmunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain. We also found that VP35 interacts with TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family. We recently reported that TRIM6 promotes the synthesis of unanchored K48-linked polyubiquitin chains, which are not covalently attached to any protein, to induce efficient antiviral IFN-I-mediated responses. Consistent with this notion, VP35 also associated noncovalently with polyubiquitin chains and inhibited TRIM6-mediated IFN-I induction. Intriguingly, we also found that TRIM6 enhances EBOV polymerase activity in a minigenome assay and TRIM6 knockout cells have reduced replication of infectious EBOV, suggesting that VP35 hijacks TRIM6 to promote EBOV replication through ubiquitination. Our work provides evidence that TRIM6 is an important host cellular factor that promotes EBOV replication, and future studies will focus on whether TRIM6 could be targeted for therapeutic intervention against EBOV infection.IMPORTANCE EBOV belongs to a family of highly pathogenic viruses that cause severe hemorrhagic fever in humans and other mammals with high mortality rates (40 to 90%). Because of its high pathogenicity and lack of licensed antivirals and vaccines, EBOV is listed as a tier 1 select-agent risk group 4 pathogen. An important mechanism for the severity of EBOV infection is its suppression of innate immune responses. The EBOV VP35 protein contributes to pathogenesis, because it serves as an essential cofactor of the viral polymerase as well as a potent antagonist of innate immunity. However, how VP35 function is regulated by host cellular factors is poorly understood. Here, we report that the host E3-ubiquitin ligase TRIM6 promotes VP35 ubiquitination and is important for efficient virus replication. Therefore, our study identifies a new host factor, TRIM6, as a potential target in the development of antiviral drugs against EBOV.

Published
2017

19. Impact of a Risk Calculator on Risk Perception and Surgical Decision Making

Author

Sacks, Greg D, Dawes, Aaron J, Ettner, Susan L, Brook, Robert H, Fox, Craig R, Russell, Marcia M, Ko, Clifford Y, and Maggard-Gibbons, Melinda

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Patient Safety, Clinical Research, Adult, Attitude of Health Personnel, Decision Making, Decision Support Techniques, Female, Humans, Judgment, Male, Middle Aged, Postoperative Complications, Risk Assessment, Surgeons, Surgical Procedures, Operative, United States, risk calculator, risk perception, surgical decision-making, variations in care, Medical and Health Sciences, Surgery, Clinical sciences
Abstract

ObjectiveThe aim of this study was to determine whether exposure to data from a risk calculator influences surgeons' assessments of risk and in turn, their decisions to operate.BackgroundLittle is known about how risk calculators inform clinical judgment and decision-making.MethodsWe asked a national sample of surgeons to assess the risks (probability of serious complications or death) and benefits (recovery) of operative and nonoperative management and to rate their likelihood of recommending an operation (5-point scale) for 4 detailed clinical vignettes wherein the best treatment strategy was uncertain. Surgeons were randomized to the clinical vignettes alone (control group; n = 384) or supplemented by data from a risk calculator (risk calculator group; n = 395). We compared surgeons' judgments and decisions between the groups.ResultsSurgeons exposed to the risk calculator judged levels of operative risk that more closely approximated the risk calculator value (RCV) compared with surgeons in the control group [mesenteric ischemia: 43.7% vs 64.6%, P < 0.001 (RCV = 25%); gastrointestinal bleed: 47.7% vs 53.4%, P < 0.001 (RCV = 38%); small bowel obstruction: 13.6% vs 17.5%, P < 0.001 (RCV = 14%); appendicitis: 13.4% vs 24.4%, P < 0.001 (RCV = 5%)]. Surgeons exposed to the risk calculator also varied less in their assessment of operative risk (standard deviations: mesenteric ischemia 20.2% vs 23.2%, P = 0.01; gastrointestinal bleed 17.4% vs 24.1%, P < 0.001; small bowel obstruction 10.6% vs 14.9%, P < 0.001; appendicitis 15.2% vs 21.8%, P < 0.001). However, averaged across the 4 vignettes, the 2 groups did not differ in their reported likelihood of recommending an operation (mean 3.7 vs 3.7, P = 0.76).ConclusionsExposure to risk calculator data leads to less varied and more accurate judgments of operative risk among surgeons, and thus may help inform discussions of treatment options between surgeons and patients. Interestingly, it did not alter their reported likelihood of recommending an operation.

Published
2016

20. Surgeon Perception of Risk and Benefit in the Decision to Operate

Author

Sacks, Greg D, Dawes, Aaron J, Ettner, Susan L, Brook, Robert H, Fox, Craig R, Maggard-Gibbons, Melinda, Ko, Clifford Y, and Russell, Marcia M

Subjects
Digestive Diseases, Patient Safety, Management of diseases and conditions, 7.3 Management and decision making, Adult, Attitude of Health Personnel, Decision Making, Female, Humans, Judgment, Male, Middle Aged, Risk Assessment, Surgeons, Surgical Procedures, Operative, behavioral science: perception, risk and benefit, surgical decision making, variations, Medical and Health Sciences, Surgery
Abstract

ObjectiveTo determine how surgeons' perceptions of treatment risks and benefits influence their decisions to operate.BackgroundLittle is known about what makes one surgeon choose to operate on a patient and another chooses not to operate.MethodsUsing an online study, we presented a national sample of surgeons (N = 767) with four detailed clinical vignettes (mesenteric ischemia, gastrointestinal bleed, bowel obstruction, appendicitis) where the best treatment option was uncertain and asked them to: (1) judge the risks (probability of serious complications) and benefits (probability of recovery) for operative and nonoperative management and (2) decide whether or not they would recommend an operation.ResultsAcross all clinical vignettes, surgeons varied markedly in both their assessments of the risks and benefits of operative and nonoperative management (narrowest range 4%-100% for all four predictions across vignettes) and in their decisions to operate (49%-85%). Surgeons were less likely to operate as their perceptions of operative risk increased [absolute difference (AD) = -29.6% from 1.0 standard deviation below to 1.0 standard deviation above mean (95% confidence interval, CI: -31.6, -23.8)] and their perceptions of nonoperative benefit increased [AD = -32.6% (95% CI: -32.8,--28.9)]. Surgeons were more likely to operate as their perceptions of operative benefit increased [AD = 18.7% (95% CI: 12.6, 21.5)] and their perceptions of nonoperative risk increased [AD = 32.7% (95% CI: 28.7, 34.0)]. Differences in risk/benefit perceptions explained 39% of the observed variation in decisions to operate across the four vignettes.ConclusionsGiven the same clinical scenarios, surgeons' perceptions of treatment risks and benefits vary and are highly predictive of their decisions to operate.

Published
2016

21. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study

Author

Ling, Walter, Hillhouse, Maureen P, Saxon, Andrew J, Mooney, Larissa J, Thomas, Christie M, Ang, Alfonso, Matthews, Abigail G, Hasson, Albert, Annon, Jeffrey, Sparenborg, Steve, Liu, David S, McCormack, Jennifer, Church, Sarah, Swafford, William, Drexler, Karen, Schuman, Carolyn, Ross, Stephen, Wiest, Katharina, Korthuis, P Todd, Lawson, William, Brigham, Gregory S, Knox, Patricia C, Dawes, Michael, and Rotrosen, John

Subjects
Biological Psychology, Psychology, Substance Misuse, Drug Abuse (NIDA only), Clinical Research, Neurosciences, Prevention, Clinical Trials and Supportive Activities, Behavioral and Social Science, Brain Disorders, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Mental health, Good Health and Well Being, Administration, Oral, Adult, Analgesics, Opioid, Buprenorphine, Naloxone Drug Combination, Cocaine-Related Disorders, Cognitive Behavioral Therapy, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Injections, Intramuscular, Male, Middle Aged, Naltrexone, Narcotic Antagonists, Treatment Outcome, Buprenorphine plus naloxone, cocaine use disorder, double-blind, multi-site trial, naltrexone, pharmacotherapy, placebo-controlled, treatment, Buprenorphine + naloxone, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Public health, Clinical and health psychology
Abstract

AimsTo examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.MethodsThis multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events.ResultsNo group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events.ConclusionsBuprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

Published
2016

22. Variation in Hospital Use of Postacute Care After Surgery and the Association With Care Quality.

Author

Sacks, Greg D, Lawson, Elise H, Dawes, Aaron J, Weiss, Robert E, Russell, Marcia M, Brook, Robert H, Zingmond, David S, and Ko, Clifford Y

Subjects
Humans, Length of Stay, Patient Discharge, Patient Readmission, Aged, Aged, 80 and over, Inpatients, Hospitals, Home Care Services, Medicare, Risk Adjustment, Quality of Health Care, Quality Indicators, Health Care, United States, Female, Male, Patient Safety, Health Services, Clinical Research, Health and social care services research, Evaluation of treatments and therapeutic interventions, 8.1 Organisation and delivery of services, 6.4 Surgery, Generic health relevance, Good Health and Well Being, hospital quality, variation in care, care coordination, surgery, post-acute care, Public Health and Health Services, Applied Economics, Health Policy & Services
Abstract

BackgroundLittle is known about hospital use of postacute care after surgery and whether it is related to measures of surgical quality.Research designWe used data merged between a national surgery registry, Medicare inpatient claims, the Area Resource File, and the American Hospital Association Annual Survey (2005-2008). Using bivariate and multivariate analyses, we calculated hospital-level, risk-adjusted rates of postacute care use for both inpatient facilities (IF) and home health care (HHC), and examined the association of these rates with hospital quality measures, including mortality, complications, readmissions, and length of stay.ResultsOf 112,620 patients treated at 217 hospitals, 18.6% were discharged to an IF, and 19.9% were discharged with HHC. Even after adjusting for differences in patient and hospital characteristics, hospitals varied widely in their use of both IF (mean, 20.3%; range, 2.7%-39.7%) and HHC (mean, 22.3%; range, 3.1%-57.8%). A hospital's risk-adjusted postoperative mortality rate or complication rate was not significantly associated with its use of postacute care, but higher 30-day readmission rates were associated with higher use of IF (24.1% vs. 21.2%, P=0.03). Hospitals with longer average length of stay used IF less frequently (19.4% vs. 24.4%, P

Published
2016

23. Nipah Virus C Protein Recruits Tsg101 to Promote the Efficient Release of Virus in an ESCRT-Dependent Pathway

Author

Park, Arnold, Yun, Tatyana, Vigant, Frederic, Pernet, Olivier, Won, Sohui T, Dawes, Brian E, Bartkowski, Wojciech, Freiberg, Alexander N, and Lee, Benhur

Subjects
Biochemistry and Cell Biology, Biological Sciences, Vaccine Related, Prevention, Biodefense, Infectious Diseases, Emerging Infectious Diseases, Infection, Blotting, Western, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, HEK293 Cells, Henipavirus Infections, Humans, Immunoprecipitation, Microscopy, Confocal, Microscopy, Electron, Transmission, Nipah Virus, Phosphoproteins, Transcription Factors, Viral Proteins, Virus Release, Microbiology, Immunology, Medical Microbiology, Virology, Medical microbiology
Abstract

The budding of Nipah virus, a deadly member of the Henipavirus genus within the Paramyxoviridae, has been thought to be independent of the host ESCRT pathway, which is critical for the budding of many enveloped viruses. This conclusion was based on the budding properties of the virus matrix protein in the absence of other virus components. Here, we find that the virus C protein, which was previously investigated for its role in antagonism of innate immunity, recruits the ESCRT pathway to promote efficient virus release. Inhibition of ESCRT or depletion of the ESCRT factor Tsg101 abrogates the C enhancement of matrix budding and impairs live Nipah virus release. Further, despite the low sequence homology of the C proteins of known henipaviruses, they all enhance the budding of their cognate matrix proteins, suggesting a conserved and previously unknown function for the henipavirus C proteins.

Published
2016

24. Relationship Between Hospital Performance on a Patient Satisfaction Survey and Surgical Quality

Author

Sacks, Greg D, Lawson, Elise H, Dawes, Aaron J, Russell, Marcia M, Maggard-Gibbons, Melinda, Zingmond, David S, and Ko, Clifford Y

Subjects
Patient Safety, Health Services, Clinical Research, Aging, 8.1 Organisation and delivery of services, Health and social care services research, Aged, Female, Health Expenditures, Hospitals, Humans, Male, Odds Ratio, Outcome Assessment, Health Care, Patient Satisfaction, Quality Improvement, Retrospective Studies, Surgical Procedures, Operative, United States
Abstract

ImportanceThe Centers for Medicare and Medicaid Services include patient experience as a core component of its Value-Based Purchasing program, which ties financial incentives to hospital performance on a range of quality measures. However, it remains unclear whether patient satisfaction is an accurate marker of high-quality surgical care.ObjectiveTo determine whether hospital performance on a patient satisfaction survey is associated with objective measures of surgical quality.Design, setting, and participantsRetrospective observational study of participating American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) hospitals. We used data from a linked database of Medicare inpatient claims, ACS NSQIP, the American Hospital Association annual survey, and Hospital Compare from December 2, 2004, through December 31, 2008. A total of 103 866 patients older than 65 years undergoing inpatient surgery were included. Hospitals were grouped by quartile based on their performance on the Hospital Consumer Assessment of Healthcare Providers and Systems survey. Controlling for preoperative risk factors, we created hierarchical logistic regression models to predict the occurrence of adverse postoperative outcomes based on a hospital's patient satisfaction scores.Main outcomes and measuresThirty-day postoperative mortality, major and minor complications, failure to rescue, and hospital readmission.ResultsOf the 180 hospitals, the overall mean patient satisfaction score was 68.0% (first quartile mean, 58.7%; fourth quartile mean, 76.7%). Compared with patients treated at hospitals in the lowest quartile, those at the highest quartile had significantly lower risk-adjusted odds of death (odds ratio = 0.85; 95% CI, 0.73-0.99), failure to rescue (odds ratio = 0.82; 95% CI, 0.70-0.96), and minor complication (odds ratio = 0.87; 95% CI, 0.75-0.99). This translated to relative risk reductions of 11.1% (P = .04), 12.6% (P = .02), and 11.5% (P = .04), respectively. No significant relationship was noted between patient satisfaction and either major complication or hospital readmission.Conclusions and relevanceUsing a national sample of hospitals, we demonstrated a significant association between patient satisfaction scores and several objective measures of surgical quality. Our findings suggest that payment policies that incentivize better patient experience do not require hospitals to sacrifice performance on other quality measures.

Published
2015

25. Which Patients Require More Care after Hospital Discharge? An Analysis of Post-Acute Care Use among Elderly Patients Undergoing Elective Surgery

Author

Sacks, Greg D, Lawson, Elise H, Dawes, Aaron J, Gibbons, Melinda M, Zingmond, David S, and Ko, Clifford Y

Subjects
Behavioral and Social Science, Cardiovascular, Clinical Research, Health Services, Patient Safety, Aging, 6.4 Surgery, Evaluation of treatments and therapeutic interventions, Age Factors, Aged, Aged, 80 and over, Elective Surgical Procedures, Female, Home Care Services, Humans, Logistic Models, Male, Patient Discharge, Postoperative Complications, Rehabilitation Centers, Risk Factors, Skilled Nursing Facilities, United States, Clinical Sciences, Surgery
Abstract

BackgroundThe use of post-acute care is common among the elderly and accounts for $62 billion in annual Medicare expenditures. However, little is known about post-acute care use after surgery.Study designData were merged between the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and Medicare claims for 2005 to 2008. Post-acute care use, including skilled nursing facilities (SNF), inpatient rehabilitation facilities (IRF), and home health care (HHC) were analyzed for 3 operations: colectomy, pancreatectomy, and open abdominal aortic aneurysm repair. Controlling for both preoperative risk factors and the occurrence of postoperative complications, we used multinomial logistic regression to estimate the odds of use for each type of post-acute care after elective surgery compared with home discharge.ResultsPost-acute care was used frequently for patients undergoing colectomy (40.0%; total n=10,932), pancreatectomy (46.0%; total n=2,144), and open abdominal aortic aneurysm (AAA) repair (44.9%; total n=1,736). Home health was the most frequently reported post-acute care service for each operation (range 23.2% to 31.5%) followed by SNF (range 12.0% to 15.0%), and then by IRF (range 2.5% to 5.4%). The majority of patients with at least 1 inpatient complication were discharged to post-acute care (range 58.6% for open AAA repair to 64.4% for colectomy). In multivariable analysis, specific preoperative risk factors, including advanced age, poor functional status, and inpatient complications were significantly associated with increased risk-adjusted odds of discharge to post-acute care for each operation studied.ConclusionsAmong elderly patients, post-acute care use is frequent after surgery and is significantly associated with several preoperative risk factors and postoperative inpatient complications. Further work is needed to ensure that post-acute care services are used appropriately and cost-effectively.

Published
2015

26. Are primary care providers prepared to care for survivors of breast cancer in the safety net?

Author

Dawes, Aaron J, Hemmelgarn, Marian, Nguyen, David K, Sacks, Greg D, Clayton, Sheilah M, Cope, Jacqueline R, Ganz, Patricia A, and Maggard‐Gibbons, Melinda

Subjects
Breast Cancer, Clinical Research, Cancer, Rehabilitation, 7.1 Individual care needs, Health and social care services research, Management of diseases and conditions, 8.1 Organisation and delivery of services, Breast Neoplasms, Data Collection, Evidence-Based Medicine, Female, Humans, Physicians, Primary Care, Practice Patterns, Physicians', Survivors, breast cancer, survivorship, safety-net providers, primary care physicians, Oncology and Carcinogenesis, Public Health and Health Services, Oncology & Carcinogenesis
Abstract

BackgroundWith the growing number of survivors of breast cancer outpacing the capacity of oncology providers, there is pressure to transition patients back to primary care. Primary care providers (PCPs) working in safety-net settings may have less experience treating survivors, and little is known about their knowledge and views on survivorship care. The current study was performed to determine the knowledge, attitudes, and confidence of PCPs in the safety net at delivering care to survivors of breast cancer.MethodsA modified version of the National Cancer Institute's Survey of Physician Attitudes Regarding Care of Cancer Survivors was given to providers at 2 county hospitals and 5 associated clinics (59 providers). Focus groups were held to understand barriers to survivorship care.ResultsAlthough the majority of providers believed PCPs have the skills necessary to provide cancer-related follow-up, the vast majority were not comfortable providing these services themselves. Providers were adherent to American Society of Clinical Oncology recommendations for mammography (98%) and physical examination (87%); less than one-third were guideline-concordant for laboratory testing and only 6 providers (10%) met all recommendations. PCPs universally requested additional training on clinical guidelines and the provision of written survivorship care plans before transfer. Concerns voiced in qualitative sessions included unfamiliarity with the management of endocrine therapy and confusion regarding who would be responsible for certain aspects of care.ConclusionsSafety-net providers currently lack knowledge of and confidence in providing survivorship care to patients with breast cancer. Opportunities exist for additional training in evidence-based guidelines and improved coordination of care between PCPs and oncology specialists.

Published
2015

27. The impact of continuous Medicaid enrollment on diagnosis, treatment, and survival in six surgical cancers.

Author

Dawes, Aaron J, Louie, Rachel, Nguyen, David K, Maggard-Gibbons, Melinda, Parikh, Punam, Ettner, Susan L, Ko, Clifford Y, and Zingmond, David S

Subjects
Humans, Neoplasms, Survival Rate, Retrospective Studies, Cohort Studies, Middle Aged, Medicaid, United States, California, Female, Male, access to care, cancer, surgery, survival, Health Policy & Services, Public Health and Health Services, Policy and Administration
Abstract

ObjectiveTo examine the effect of Medicaid enrollment on the diagnosis, treatment, and survival of six surgically relevant cancers among poor and underserved Californians.Data sourcesCalifornia Cancer Registry (CCR), California's Patient Discharge Database (PDD), and state Medicaid enrollment files between 2002 and 2008.Study designWe linked clinical and administrative records to differentiate patients continuously enrolled in Medicaid from those receiving coverage at the time of their cancer diagnosis. We developed multivariate logistic regression models to predict death within 1 year for each cancer after controlling for sociodemographic and clinical variables.Data collection/extraction methodsAll incident cases of six cancers (colon, esophageal, lung, pancreas, stomach, and ovarian) were identified from CCR. CCR records were linked to hospitalizations (PDD) and monthly Medicaid enrollment.Principal findingsContinuous enrollment in Medicaid for at least 6 months prior to diagnosis improves survival in three surgically relevant cancers. Discontinuous Medicaid patients have higher stage tumors, undergo fewer definitive operations, and are more likely to die even after risk adjustment.ConclusionsExpansion of continuous insurance coverage under the Affordable Care Act is likely to improve both access and clinical outcomes for cancer patients in California.

Published
2014

28. Red brain, blue brain: evaluative processes differ in Democrats and Republicans.

Author

Schreiber, Darren, Fonzo, Greg, Simmons, Alan N, Dawes, Christopher T, Flagan, Taru, Fowler, James H, and Paulus, Martin P

Subjects
Amygdala, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Attitude, Risk-Taking, Decision Making, Judgment, Politics, Adult, Female, Male, General Science & Technology
Abstract

Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli.

Published
2013

29. Health care utilization and outcomes in older adults after Traumatic Brain Injury: A CENTER-TBI study

Author

van der Vlegel, Marjolein, Mikolić, Ana, Wilson, Lindsay, Gomez, Pedro A., Lagares, Alfonso, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Vargiolu, Alessia, Ceyisakar, Iris, Gravesteijn, Benjamin, Haagsma, Juanita A., Huijben, Jilske, Maas, Andrew I. R., Lingsma, Hester, Nieboer, Daan, Mikolic, Ana, Polinder, Suzanne, Sewalt, Charlie, Steyerberg, Ewout W., Velt, Kimberley, Voormolen, Daphne, Wiegers, Eveline, Peul, Wilco, van Dijck, Jeroen T. J. M., van Essen, Thomas A., van Wijk, Roel P. J., Clusmann, Hans, Coburn, Mark, Kowark, Ana, Rossaint, Rolf, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čovid, Amra, von Steinbüchel, Nicole, Curry, Nicola, Stanworth, Simon, Dahyot-Fizelier, Claire, Dark, Paul, Johnson, Faye, Dawes, Helen, Esser, Patrick, van Heugten, Caroline, CENTER-TBI Participants and Investigators, De Keyser, Véronique, Menovsky, Tomas, Van der Steen, Gregory, Della Corte, Francesco, Grossi, Francesca, Depreitere, Bart, Đilvesi, Đula, Golubovic, Jagoš, Karan, Mladen, Åkerlund, Cecilia, Vulekovic, Petar, Dreier, Jens, Vajkoczy, Peter, Wolf, Stefan, Dulière, Guy-Loup, Maréchal, Hugues, Fabricius, Martin, Kondziella, Daniel, Feigin, Valery L., Jones, Kelly, George, Pradeep, Ao, Braden Te, Theadom, Alice, Foks, Kelly, Haitsma, Iain, Volovici, Victor, Furmanov, Alex, Rosenthal, Guy, Gagliardo, Pablo, Gao, Guoyi, Jiang, Ji-yao, Lanyon, Linda, Ghuysen, Alexandre, Giga, Lelde, Valeinis, Egils, Ziverte, Agate, Glocker, Ben, Rueckert, Daniel, Gratz, Johannes, Gruen, Russell L., Gupta, Deepak, Roe, Cecilie, Muraleedharan, Visakh, Helseth, Eirik, Roise, Olav, Horton, Lindsay, Hutchinson, Peter J., Kolias, Angelos G., Jacobs, Bram, van der Naalt, Joukje, Jankowski, Stefan, Kompanje, Erwin, Nelson, David, Timmers, Marjolein, Laureys, Steven, Ledoux, Didier, Misset, Benoit, Lecky, Fiona, Olubukola, Otesile, Lefering, Rolf, Schäfer, Nadine, Legrand, Valerie, Lejeune, Aurelie, Lee Hee, Quentin, Amrein, Krisztina, Vega, Emmanuel, Mattern, Julia, Levi, Leon, Lightfoot, Roger, Maegele, Marc, Manara, Alex, Thomas, Matt, Manley, Geoffrey, Martino, Costanza, Sakowitz, Oliver, Ezer, Erzsébet, Sanchez-Porras, Renan, Younsi, Alexander, McMahon, Catherine, Negru, Ancuta, Oresic, Matej, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Persona, Paolo, Piippo-Karjalainen, Anna, Kovács, Noémi, Pirinen, Matti, Ples, Horia, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Melegh, Béla, Ripatti, Samuli, Rocka, Saulius, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rossi, Sandra, Rusnák, Martin, Sahuquillo, Juan, Sandor, Janos, Schmidt, Silke, Schoechl, Herbert, Nyirádi, József, Schoonman, Guus, Skandsen, Toril, Stevens, Robert, Stewart, William, Takala, Riikka, Tamosuitis, Tomas, Tenovuo, Olli, Tibboel, Dick, Tolias, Christos, Tudora, Cristina Maria, Tamás, Viktória, van der Jagt, Mathieu, Van Hecke, Wim, Van Praag, Dominique, Vyvere, Thijs Vande, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Wang, Kevin K. W., Yang, Zhihui, Vámos, Zoltán, Ylén, Peter, Sorinola, Abayomi, Andelic, Nada, Andreassen, Lasse, Kaplan, Z. L. Rana, Anke, Audny, Frisvold, Shirin, Antoni, Anna, Schwendenwein, Elisabeth, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Beretta, Luigi, Calvi, Maria Rosa, Bartels, Ronald, Retel Helmrich, Isabel R. A., Boogert, Hugo den, Barzó, Pál, Beauvais, Romuald, Perera, Natascha, Beer, Ronny, Helbok, Raimund, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Degos, Vincent, van Veen, Ernest, Galanaud, Damien, Perlbarg, Vincent, Berardino, Maurizio, Cavallo, Simona, Blaabjerg, Morten, Rosenlund, Christina, Schou, Rico Frederik, Bragge, Peter, Brazinova, Alexandra, Majdan, Marek, Taylor, Mark Steven, Zelinkova, Veronika, Brinck, Vibeke, Jarrett, Mike, Brooker, Joanne, Donoghue, Emma, Synnot, Anneliese, Brorsson, Camilla, Koskinen, Lars-Owe, Sundström, Nina, Steinbuechel, Nicole V., Buki, Andras, Czeiter, Endre, Bullinger, Monika, Cabeleira, Manuel, Czosnyka, Marek, Dixit, Abhishek, Ercole, Ari, Koraropoulos, Evgenios, Menon, David, Newcombe, Virginia, Plass, Anne Marie, Richter, Sophie, Smielewski, Peter, Stamatakis, Emmanuel, Williams, Guy, Winzeck, Stefan, Zeiler, Frederick A., Caccioppola, Alessio, Calappi, Emiliana, Carbonara, Marco, Ortolano, Fabrizio, Zeldovich, Marina, Zoerle, Tommaso, Stocchetti, Nino, Cameron, Peter, Gantner, Dashiell, Murray, Lynnette, Trapani, Tony, Vallance, Shirley, Lozano, Guillermo Carbayo, Pomposo, Inigo, Castaño-León, Ana M., Molecular Neuroscience and Ageing Research (MOLAR), CENTER-TBI Participants and Investigators, van der Vlegel, M, Mikolić, A, Hee, Q, Kaplan, Z, Helmrich, I, van Veen, E, Andelic, N, Steinbuechel, N, Plass, A, Zeldovich, M, Wilson, L, Maas, A, Haagsma, J, Polinder, S, Åkerlund, C, George, P, Lanyon, L, Muraleedharan, V, Nelson, D, Amrein, K, Ezer, E, Kovács, N, Melegh, B, Nyirádi, J, Tamás, V, Vámos, Z, Sorinola, A, Andreassen, L, Anke, A, Frisvold, S, Antoni, A, Schwendenwein, E, Audibert, G, Azouvi, P, Azzolini, M, Beretta, L, Calvi, M, Bartels, R, Boogert, H, Barzó, P, Beauvais, R, Perera, N, Beer, R, Helbok, R, Bellander, B, Belli, A, Benali, H, Degos, V, Galanaud, D, Perlbarg, V, Berardino, M, Cavallo, S, Blaabjerg, M, Rosenlund, C, Schou, R, Bragge, P, Brazinova, A, Majdan, M, Taylor, M, Zelinkova, V, Brinck, V, Jarrett, M, Brooker, J, Donoghue, E, Synnot, A, Brorsson, C, Koskinen, L, Sundström, N, Buki, A, Czeiter, E, Bullinger, M, Cabeleira, M, Czosnyka, M, Dixit, A, Ercole, A, Koraropoulos, E, Menon, D, Newcombe, V, Richter, S, Smielewski, P, Stamatakis, E, Williams, G, Winzeck, S, Zeiler, F, Caccioppola, A, Calappi, E, Carbonara, M, Ortolano, F, Zoerle, T, Stocchetti, N, Cameron, P, Gantner, D, Murray, L, Trapani, T, Vallance, S, Lozano, G, Pomposo, I, Castaño-León, A, Gomez, P, Lagares, A, Chevallard, G, Chieregato, A, Citerio, G, Vargiolu, A, Ceyisakar, I, Gravesteijn, B, Huijben, J, Lingsma, H, Nieboer, D, Mikolic, A, Sewalt, C, Steyerberg, E, Velt, K, Voormolen, D, Wiegers, E, Peul, W, van Dijck, J, van Essen, T, van Wijk, R, Clusmann, H, Coburn, M, Kowark, A, Rossaint, R, Coles, J, Cooper, J, Correia, M, Čovid, A, von Steinbüchel, N, Curry, N, Stanworth, S, Dahyot-Fizelier, C, Dark, P, Johnson, F, Dawes, H, Esser, P, van Heugten, C, De Keyser, V, Menovsky, T, Van der Steen, G, Corte, F, Grossi, F, Depreitere, B, Đilvesi, Đ, Golubovic, J, Karan, M, Vulekovic, P, Dreier, J, Vajkoczy, P, Wolf, S, Dulière, G, Maréchal, H, Fabricius, M, Kondziella, D, Feigin, V, Jones, K, Ao, B, Theadom, A, Foks, K, Haitsma, I, Volovici, V, Furmanov, A, Rosenthal, G, Gagliardo, P, Gao, G, Jiang, J, Ghuysen, A, Giga, L, Valeinis, E, Ziverte, A, Glocker, B, Rueckert, D, Gratz, J, Gruen, R, Gupta, D, Roe, C, Helseth, E, Roise, O, Horton, L, Hutchinson, P, Kolias, A, Jacobs, B, van der Naalt, J, Jankowski, S, Kompanje, E, Timmers, M, Laureys, S, Ledoux, D, Misset, B, Lecky, F, Olubukola, O, Lefering, R, Schäfer, N, Legrand, V, Lejeune, A, Vega, E, Mattern, J, Levi, L, Lightfoot, R, Maegele, M, Manara, A, Thomas, M, Manley, G, Martino, C, Sakowitz, O, Sanchez-Porras, R, Younsi, A, Mcmahon, C, Negru, A, Oresic, M, Palotie, A, Parizel, P, Payen, J, Persona, P, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Ripatti, S, Rocka, S, Rosand, J, Rosenfeld, J, Rossi, S, Rusnák, M, Sahuquillo, J, Sandor, J, Schmidt, S, Schoechl, H, Schoonman, G, Skandsen, T, Stevens, R, Stewart, W, Takala, R, Tamosuitis, T, Tenovuo, O, Tibboel, D, Tolias, C, Tudora, C, van der Jagt, M, Van Hecke, W, Van Praag, D, Vyvere, T, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Wang, K, Yang, Z, Ylén, P, Public Health, Otorhinolaryngology and Head and Neck Surgery, Intensive Care, Neurology, Neurosurgery, Pediatric Surgery, University of Helsinki, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Department of Mathematics and Statistics, Helsinki Institute for Information Technology, Statistical and population genetics, Clinicum, Helsinki University Hospital Area, Neurokirurgian yksikkö, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, Samuli Olli Ripatti / Principal Investigator, and Complex Disease Genetics

Subjects
Traumatic, Quality of Life/psychology, Traumatic Brain Injury, Health-related quality of life, Health care utilization, 3112 Neurosciences, Glasgow Outcome Scale, Outcomes, Patient Acceptance of Health Care, SDG 3 - Good Health and Well-being, Older adults, Brain Injuries, Brain Injuries, Traumatic, Quality of Life, Humans, General Earth and Planetary Sciences, Mental health, 3111 Biomedicine, Prospective Studies, Human medicine, Older adult, Aged, Outcome, General Environmental Science
Abstract

Injury : international journal of the care of the injured 53(8), 2774-2782 (2022). doi:10.1016/j.injury.2022.05.009, Published by Elsevier Science, Amsterdam [u.a.]

Published
2022

30. Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury

Author

Bockhop, Fabian, Zeldovich, Marina, Cunitz, Katrin, Van Praag, Dominique, van der Vlegel, Marjolein, Beissbarth, Tim, Hagmayer, York, von Steinbuechel, Nicole, Åkerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny Gabriele Wagner, Antoni, Anna, Audibert, Gérard, Azouvi, Philippe, Azzolini, Maria Luisa, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, L. Gruen, Russell, Gupta, Deepak, A. Haagsma, Juanita, Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, G. Kolias, Angelos, Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, I.R. Maas, Andrew, Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Helmrich, Isabel Retel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Røe, Cecilie, Røise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, RueckertMartin Rusnák, Daniel, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Steven Taylor, Mark, Te Ao, Braden, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Maria Tudora, Cristina, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, Naalt, Joukje van der, T.J.M. van Dijck, Jeroen, van Erp, Inge A. M., van Essen, Thomas A., Hecke, Wim Van, van Heugten, Caroline, van Veen, Ernest, Vande Vyvere, Thijs, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, K.W. Wang, Kevin, Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Apollo - University of Cambridge Repository, Ragauskas, Arminas, Rocka, Saulius, Tamosuitis, Tomas, Vilcinis, Rimantas, „Springer Nature' grupė, Ročka, Saulius, Tamošuitis, Tomas, CTR-TBI Participants Investigators, Molecular Neuroscience and Ageing Research (MOLAR), Public Health, Amrein, Krisztina, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Kornaropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Andelic, Nada, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Andreassen, Lasse, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Anke, Audny, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Antoni, Anna, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Audibert, Gérard, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Pisica, Dana, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Azouvi, Philippe, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Raj, Rahul, Rambadagalla, Malinka, Retel Helmrich, Isabel, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Azzolini, Maria Luisa, Ripatti, Samuli, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Bartels, Ronald, Rueckert, Martin, Rusnák, Daniel, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Barzó, Pál, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Singh, Ranjit D., Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Beauvais, Romuald, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Takala, Riikka, Tamás, Viktória, Taylor, Mark Steven, Te Ao, Braden, Tenovuo, Olli, Beer, Ronny, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Bellander, Bo-Michael, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, van der Naalt, Joukje, van Dijck, Jeroen T. J. M., van Erp, Inge A. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Belli, Antonio, Van Praag, Dominique, van Veen, Ernest, Vande Vyvere, Thijs, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Benali, Habib, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Whitehouse, Daniel, Wiegers, Eveline, Williams, Guy, Wilson, Lindsay, Berardino, Maurizio, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Åkerlund, Cecilia, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Bockhop, F, Zeldovich, M, Cunitz, K, Van Praag, D, van der Vlegel, M, Beissbarth, T, Hagmayer, Y, von Steinbuechel, N, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini Maria, L, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi Maria, R, Cameron, P, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Clusmann, H, Coburn, M, Coles, J, Cooper Jamie, D, Correia, M, Čović, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin Valery, L, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Guoyi Gao, N, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, A., G, Gratz, J, Gravesteijn, B, Grossi, F, L., G, Gupta, D, A., H, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, J., H, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, G., K, Kompanje, E, Kondziella, D, Kornaropoulos, E, Koskinen, L, Kovács, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, I. R., M, Castaño-León Ana, M, Maegele, M, Majdan, M, Manara, A, Manley, G, Martino, C, Maréchal, H, Mattern, J, Mcmahon, C, Melegh, B, Menon, D, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyirádi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel Paul, M, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Pisica, D, Ples, H, Polinder, S, Pomposo, I, Posti Jussi, P, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Helmrich Isabel, R, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roe, C, Roise, O, Rosand, J, Rosenfeld Jeffrey, V, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, RueckertMartin Rusnák, D, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schäfer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou Rico, F, Schwendenwein, E, Sewalt, C, Singh Ranjit, D, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg Ewout, W, Stocchetti, N, Sundström, N, Takala, R, Tamás, V, Tamosuitis, T, Steven Taylor, M, Te Ao, B, Tenovuo, O, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Maria Tudora, C, Unterberg, A, Vajkoczy, P, Vallance, S, Valeinis, E, Vámos, Z, van der Jagt, M, Van der Steen, G, Naalt Joukje van, D, T. J. M., V, van Erp Inge, A, van Essen Thomas, A, Hecke Wim, V, van Heugten, C, van Veen, E, Vande Vyvere, T, van Wijk Roel, P, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa Paul, M, Vik, A, Vilcinis, R, Volovici, V, von Steinbüchel, N, Voormolen, D, Vulekovic, P, K. W., W, Whitehouse, D, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Ylén, P, Younsi, A, Zeiler Frederick, A, Zelinkova, V, Ziverte, A, Zoerle, T, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Statistical and population genetics, Clinicum, Helsinki University Hospital Area, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, Samuli Olli Ripatti / Principal Investigator, and Complex Disease Genetics

Subjects
Post-Traumatic/psychology, Multidisciplinary, Traumatic/complications, Brain Injuries, Traumatic/complications, 3124 Neurology and psychiatry, Diagnostic and Statistical Manual of Mental Disorder, Stress Disorders, Post-Traumatic/psychology, Checklist, Diagnostic and Statistical Manual of Mental Disorders, Stress Disorders, Post-Traumatic, Brain Injuries, Brain Injuries, Traumatic, Humans, Human medicine, Human, Stress Disorders, Language
Abstract

Scientific reports 12, 16571 (2022). doi:10.1038/s41598-022-20170-2, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Published
2022

31. Increased frequency of alpha-synuclein in the substantia nigra in human immunodeficiency virus infection.

Author

Khanlou, Negar, Moore, David J, Chana, Gursharan, Cherner, Mariana, Lazzaretto, Deborah, Dawes, Sharron, Grant, Igor, Masliah, Eliezer, Everall, Ian P, and HNRC Group

Subjects
HNRC Group, Substantia Nigra, Humans, HIV, HIV Infections, Neurodegenerative Diseases, Immunohistochemistry, Age Factors, Up-Regulation, Aged, Middle Aged, Female, Male, alpha-Synuclein, Amyloid beta-Peptides, Biomarkers, aging, brain pathology, cognition, substantia nigra, HIV/AIDS, Clinical Research, Aging, Infectious Diseases, Dementia, Acquired Cognitive Impairment, Brain Disorders, Neurodegenerative, Neurosciences, Parkinson's Disease, 2.1 Biological and endogenous factors, Infection, Neurological, Virology, Clinical Sciences, Medical Microbiology
Abstract

The frequency of neurodegenerative markers among long surviving human immunodeficiency virus (HIV)-infected individuals is unknown, therefore, the present study investigated the frequency of alpha-synuclein, beta-amyloid, and HIV-associated brain pathology in the brains of older HIV-infected individuals. We examined the substantia nigra of 73 clinically well-characterized HIV-infected individuals aged 50 to 76 years from the National NeuroAIDS Tissue Consortium. We also examined the frontal and temporal cortical regions of a subset of 36 individuals. Neuritic alpha-synuclein expression was found in 16% (12/73) of the substantia nigra of the HIV+cases and none of the older control cases (0/18). beta-Amyloid deposits were prevalent and found in nearly all of the HIV+cases (35/36). Despite these increases of degenerative pathology, HIV-associated brain pathology was present in only 10% of cases. Among older HIV+adults, HIV-associated brain pathology does not appear elevated; however, the frequency of both alpha-synuclein and beta-amyloid is higher than that found in older healthy persons. The increased prevalence of alpha-synuclein and beta-amyloid in the brains of older HIV-infected individuals may predict an increased risk of developing neurodegenerative disease.

Published
2009

32. Increased frequency of α-synuclein in the substantia nigra in human immunodeficiency virus infection

Author

Khanlou, Negar, Moore, David J, Chana, Gursharan, Cherner, Mariana, Lazzaretto, Deborah, Dawes, Sharron, Grant, Igor, Masliah, Eliezer, Everall, Ian P, and the HNRC Group

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Neurodegenerative, Infectious Diseases, HIV/AIDS, Clinical Research, Acquired Cognitive Impairment, Aging, Brain Disorders, Neurosciences, Dementia, Aetiology, 2.1 Biological and endogenous factors, Neurological, Infection, Age Factors, Aged, Amyloid beta-Peptides, Biomarkers, Female, HIV, HIV Infections, Humans, Immunohistochemistry, Male, Middle Aged, Neurodegenerative Diseases, Substantia Nigra, Up-Regulation, alpha-Synuclein, aging, brain pathology, cognition, substantia nigra, HNRC Group, Clinical Sciences, Virology, Clinical sciences, Medical microbiology
Abstract

The frequency of neurodegenerative markers among long surviving human immunodeficiency virus (HIV)-infected individuals is unknown, therefore, the present study investigated the frequency of alpha-synuclein, beta-amyloid, and HIV-associated brain pathology in the brains of older HIV-infected individuals. We examined the substantia nigra of 73 clinically well-characterized HIV-infected individuals aged 50 to 76 years from the National NeuroAIDS Tissue Consortium. We also examined the frontal and temporal cortical regions of a subset of 36 individuals. Neuritic alpha-synuclein expression was found in 16% (12/73) of the substantia nigra of the HIV+cases and none of the older control cases (0/18). beta-Amyloid deposits were prevalent and found in nearly all of the HIV+cases (35/36). Despite these increases of degenerative pathology, HIV-associated brain pathology was present in only 10% of cases. Among older HIV+adults, HIV-associated brain pathology does not appear elevated; however, the frequency of both alpha-synuclein and beta-amyloid is higher than that found in older healthy persons. The increased prevalence of alpha-synuclein and beta-amyloid in the brains of older HIV-infected individuals may predict an increased risk of developing neurodegenerative disease.

Published
2009

34. Policy Forum: Studying Eyewitness Investigations in the Field

Author

Schacter, Daniel L, Dawes, Robyn, Jacoby, Larry L, Kahneman, Daniel, Lempert, Richard, Roediger, Henry L, and Rosenthal, Robert

Subjects
Criminology, Human Society, Crime Victims, Diffusion of Innovation, Double-Blind Method, Humans, Police, Recognition, Psychology, United States, eyewitness identification, double blind sequential procedure, field studies, Psychology, Cognitive Sciences, Law, Law in context, Applied and developmental psychology
Abstract

This article considers methodological issues arising from recent efforts to provide field tests of eyewitness identification procedures. We focus in particular on a field study (Mecklenburg 2006) that examined the "double blind, sequential" technique, and consider the implications of an acknowledged methodological confound in the study. We explain why the confound has severe consequences for assessing the real-world implications of this study.

Published
2008

35. The chicken or the egg? Testing temporal relations between academic support, self-efficacy, outcome expectations, and goal progress among college students

Author

Hung-Bin Sheu, Shiqin Stephanie Chong, and Mary E. Dawes

Subjects
Male, Motivation, Psychiatry and Mental health, Clinical Psychology, Universities, Social Psychology, Humans, Female, General Medicine, Students, Goals, Self Efficacy
Abstract

This study was designed to examine the directionality of short-term temporal relations between academic support, self-efficacy, outcome expectations, and goal progress, which are hypothesized as mediators that channel the effects of personality and affective variables on academic well-being. Using the random intercepts cross-lagged panel model (RI-CLPM) approach, four temporal models were tested on data of 825 first-year students gathered at three time points as they began their college journey. Based on the entire sample, the retained model revealed bidirectional relations between support and self-efficacy, support and outcome expectations, and self-efficacy and goal progress in the second time lag. A similar pattern emerged for male students, demonstrating a full reciprocal link between self-efficacy and goal progress and mediational pathways from these two variables to support and outcome expectations over time. For students of color, the results identified academic support as the temporal precursor of self-efficacy and outcome expectations, and self-efficacy as the antecedent of outcome expectations and goal progress. On the other hand, data of female students and those of European American students yielded less conclusive temporal patterns. These findings shed light on how temporal relations between academic support, self-efficacy, outcome expectations, and goal progress might vary as a function of one's gender and racial/ethnic backgrounds. They also offer practical implications for selecting and organizing intervention strategies designed to promote students' academic adjustment and well-being during their initial transition to college. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Published
2022

36. Kinanthropometric Characteristic Comparisons of NCAA Division I Offensive and Defensive Linemen Spanning 8 Decades

Author

Bert H, Jacobson, Jay, Dawes, Doug, Smith, and Quincy, Johnson

Subjects
Universities, Soccer, Body Composition, Football, Humans, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, General Medicine, Body Height
Abstract

Jacobson, BH, Dawes, J, Smith, D, and Johnson, Q. Kinanthropometric characteristic comparisons of NCAA Division I offensive and defensive linemen spanning eight decades. J Strength Cond Res 36(12): 3404-3408, 2022-College football players have gained body mass, stature, and speed since the inception of the game. Of particular note is the body mass gain of NCAA Division I offensive linemen (OL) and defensive linemen (DL). The primary purpose of this study was to compare body mass and stature of OL and DL for each decade since 1950 and to subsequently compare speed using more recently available NFL Combine data to determine if the rates of gain have been consistent or is waning. Ten universities were randomly chosen from the "Power Five" conferences based on the prominence of their football programs. Recorded data included players' body mass, stature, and available 40 yd times. For each team, 8 OL and 8 DL were chosen, totaling 80 OL and 80 DL. Results indicated that body mass increased significantly ( p0.05) for both OL and DL (57.9 and 54.4%, respectively). However, the rate of weight gain for either OL or DL was not linear. Both OL and DL consistently increased in height from 1950 with OL and DL increasing 12.7 cm (5.0 in) and 11.4 cm (4.7 in), respectively. In addition, 40 yd times have improved over the 3 available decades (2000-2020). The 2020 times were significantly faster than the 2000 for both OL and DL. These findings may have profound implications related to player safety. The overall increases in body mass of linemen in combination with greater speed may result in have devastating consequences to the human body in a contact/collision sport such as football. Indeed, new rules are being considered to reduce debilitating injures.

Published
2022

37. Consensus Quality Measures and Dose Constraints for Rectal Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology (ASTRO) Expert Panel

Author

John Park, Bhanu Prasad Venkatesulu, Ksenija Kujundzic, Evangelia Katsoulakis, Abhishek A. Solanki, Lindsay L. Puckett, Rishabh Kapoor, Christina H. Chapman, Michael Hagan, Maria D. Kelly, Jatinder Palta, Jonathan B. Ashman, Dustin Jacqmin, Lisa A. Kachnic, Bruce D. Minsky, Jeffrey Olsen, Ann C. Raldow, Jennifer Y. Wo, Samantha Dawes, Emily Wilson, Randi Kudner, and Prajnan Das

Subjects
Consensus, Oncology, Rectal Neoplasms, Radiation Oncology, Humans, Radiology, Nuclear Medicine and imaging, United States, Quality Indicators, Health Care, Veterans
Abstract

Ensuring high quality, evidence-based radiation therapy for patients with cancer is of the upmost importance. To address this need, the Veterans Affairs (VA) Radiation Oncology Program partnered with the American Society for Radiation Oncology and established the VA Radiation Oncology Quality Surveillance program. As part of this ongoing effort to provide the highest quality of care for patients with rectal cancer, a blue-ribbon panel comprised of rectal cancer experts was formed to develop clinical quality measures.The Rectal Cancer Blue Ribbon panel developed quality, surveillance, and aspirational measures for (a) initial consultation and workup, (b) simulation, treatment planning, and treatment, and (c) follow-up. Twenty-two rectal cancer specific measures were developed (19 quality, 1 aspirational, and 2 surveillance). In addition, dose-volume histogram constraints for conventional and hypofractionated radiation therapy were created.The quality measures and dose-volume histogram for rectal cancer serves as a guideline to assess the quality of care for patients with rectal cancer receiving radiation therapy. These quality measures will be used for quality surveillance for veterans receiving care both inside and outside the VA system to improve the quality of care for these patients.

Published
2022

38. Consensus Quality Measures and Dose Constraints for Head and Neck Cancer with an emphasis on Oropharyngeal and Laryngeal Cancer from the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel

Author

Evangelia Katsoulakis, Randi Kudner, Christina Chapman, John Park, Lindsay Puckett, Abhi Solanki, Rishabh Kapoor, Michael Hagan, Maria Kelly, Jatinder Palta, Roy Tishler, Ying Hitchcock, Bhisham Chera, Vladimir Feygelman, Gary Walker, David Sher, Ksenija Kujundzic, Emily Wilson, Samantha Dawes, Sue S. Yom, and Louis Harrison

Subjects
Consensus, Oncology, Head and Neck Neoplasms, Quality of Life, Radiation Oncology, Humans, Radiology, Nuclear Medicine and imaging, Laryngeal Neoplasms, United States, Quality Indicators, Health Care, Veterans
Abstract

Safeguarding high-quality care using evidence-based radiation therapy for patients with head and neck cancer is crucial to improving oncologic outcomes, including survival and quality of life.The Veterans Administration (VA) National Radiation Oncology Program established the VA Radiation Oncology Quality Surveillance Program (VAROQS) to develop clinical quality measures (QM) in head and neck cancer. As part of the development of QM, the VA commissioned, along with the American Society for Radiation Oncology, a blue-ribbon panel comprising experts in head and neck cancer, to develop QM.We describe the methods used to develop QM and the final consensus QM, as well as aspirational and surveillance QM, which capture all aspects of the continuum of patient care from initial patient work-up, radiation treatment planning and delivery, and follow-up care, as well as dose volume constraints.These QM are intended for use as part of ongoing quality surveillance for veterans receiving radiation therapy throughout the VA as well as outside the VA. They may also be used by the non-VA community as a basic measure of quality care for head and neck cancer patients receiving radiation.

Published
2022

39. A Prospective Randomized Controlled Trial of Methylprednisolone for Postoperative Pain Management of Surgically Treated Distal Radius Fractures

Author

Michael B, Gottschalk, Alexander, Dawes, John, Hurt, Corey, Spencer, Collier, Campbell, Roy, Toston, Kevin, Farley, Charles, Daly, and Eric R, Wagner

Subjects
Analgesics, Opioid, Fracture Fixation, Internal, Pain, Postoperative, Humans, Orthopedics and Sports Medicine, Surgery, Prospective Studies, Radius Fractures, Methylprednisolone, Dexamethasone
Abstract

Perioperative glucocorticoids have been effectively used as a pain management regimen for reducing pain after hand surgery. We hypothesize that a methylprednisolone taper (MPT) course following surgery will reduce pain and opioid consumption in the early postoperative period.This study was a randomized controlled trial of patients undergoing surgical fixation for distal radius fracture. Before surgery, patients were randomly assigned to receive preoperative dexamethasone only or preoperative dexamethasone followed by a 6-day oral MPT. Patient pain and opioid consumption data were collected for 7 days after surgery using a patient-reported pain journal.Our study consisted of 56 patients enrolled from November 2018 to March 2020. Twenty-eight patients each were assigned to the control and treatment groups. Demographic characteristics such as age, body mass index, the dominant side affected, smoking status, diabetes status, and current narcotic use were similar between the control and treatment groups. With a noticeable, significant reduction starting on postoperative day 2, patients who received an MPT course consumed substantially less opioids during the first 7 days (7.8 ± 7.2 pills compared with 15.5 ± 11.5 pills, a 50% reduction). These patients also consumed significantly fewer oral morphine equivalents than the control group (81.2 vs 41.2). A significant difference in the pain visual analog scale scores between the 2 groups was noted starting on postoperative day 2, with 48% of the treatment group reporting no pain by postoperative day 6. No adverse events, including infection or complications of wound or bone healing, were seen in either group.There was an early improvement in pain and reduction in early opioid consumption with a 6-day MPT following surgical fixation for distal radius fracture. With no increased risk of adverse events in our sample, MPT may be a safe and effective way to reduce postoperative pain.Therapeutic II.

Published
2022

40. Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial

Author

Ellen J. Kim, Aaron R. Mangold, Jennifer A. DeSimone, Henry K. Wong, Lucia Seminario-Vidal, Joan Guitart, James Appel, Larisa Geskin, Edward Lain, Neil J. Korman, Nathalie Zeitouni, Neda Nikbakht, Kenneth Dawes, Oleg Akilov, Joi Carter, Michi Shinohara, Timothy M. Kuzel, Warren Piette, Neal Bhatia, Amy Musiek, David Pariser, Youn H. Kim, Dirk Elston, Erin Boh, Madeleine Duvic, Auris Huen, Theresa Pacheco, Jeffrey P. Zwerner, Seung Tae Lee, Michael Girardi, Christiane Querfeld, Kimberly Bohjanen, Elise Olsen, Gary S. Wood, Adam Rumage, Oreola Donini, Andrea Haulenbeek, Christopher J. Schaber, Richard Straube, Christopher Pullion, Alain H. Rook, and Brian Poligone

Subjects
Adult, Anthracenes, Male, Photosensitizing Agents, Skin Neoplasms, Dermatology, Middle Aged, Lymphoma, T-Cell, Cutaneous, Ointments, Mycosis Fungoides, Treatment Outcome, Photochemotherapy, Humans, Female, Triazenes, Perylene
Abstract

ImportanceGiven that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).ObjectivesTo determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.Design, Settings, and ParticipantsThis was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL.InterventionsIn cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks.Main Outcomes and MeasuresThe primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.ResultsThe study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P P Conclusion and RelevanceThe findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.Trial RegistrationClinicalTrials.gov Identifier: NCT02448381

Published
2023

41. Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis

Author

Böhm J. K., Schaeben V., Schäfer N., Güting H., Lefering R., Thorn S., Schöchl H., Zipperle J., Grottke O., Rossaint R., Stanworth S., Curry N., Maegele M., Åkerlund C., Amrein K., Andelic N., Andreassen L., Anke A., Antoni A., Audibert G., Azouvi P., Azzolini M. L., Bartels R., Barzó P., Beauvais R., Beer R., Bellander B. M., Belli A., Benali H., Berardino M., Beretta L., Blaabjerg M., Bragge P., Brazinova A., Brinck V., Brooker J., Brorsson C., Buki A., Bullinger M., Cabeleira M., Caccioppola A., Calappi E., Calvi M. R., Cameron P., Lozano G. C., Carbonara M., Cavallo S., Chevallard G., Chieregato A., Citerio G., Ceyisakar I., Clusmann H., Coburn M., Coles J., Cooper J. D., Correia M., Čović A., Czeiter E., Czosnyka M., Dahyot-Fizelier C., Dark P., Dawes H., De Keyser V., Degos V., Corte F. D., Boogert H. d., Depreitere B., Đilvesi Đ., Dixit A., Donoghue E., Dreier J., Dulière G. L., Ercole A., Esser P., Ezer E., Fabricius M., Feigin V. L., Foks K., Frisvold S., Furmanov A., Gagliardo P., Galanaud D., Gantner D., Gao G., George P., Ghuysen A., Giga L., Glocker B., Golubovic J., Gomez P. A., Gratz J., Gravesteijn B., Grossi F., Gruen R. L., Gupta D., Haagsma J. A., Haitsma I., Helbok R., Helseth E., Horton L., Molecular Neuroscience and Ageing Research (MOLAR), Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J., Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Johnson, Faye, Jones, Kelly, Karan, Mladen, Kolias, Angelos G., Kompanje, Erwin, Kondziella, Daniel, Koraropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Kowark, Ana, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lecky, Fiona, Ledoux, Didier, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lingsma, Hester, Maas, Andrew I. R., Castaño-León, Ana M., Maegele, Marc, Majdan, Marek, Manara, Alex, Manley, Geoffrey, Martino, Costanza, Maréchal, Hugues, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Åkerlund, Cecilia, Menon, David, Menovsky, Tomas, Mikolic, Ana, Misset, Benoit, Muraleedharan, Visakh, Murray, Lynnette, Negru, Ancuta, Nelson, David, Newcombe, Virginia, Nieboer, Daan, Amrein, Krisztina, Nyirádi, József, Olubukola, Otesile, Oresic, Matej, Ortolano, Fabrizio, Palotie, Aarno, Parizel, Paul M., Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Andelic, Nada, Peul, Wilco, Piippo-Karjalainen, Anna, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P., Puybasset, Louis, Radoi, Andreea, Ragauskas, Arminas, Andreassen, Lasse, Raj, Rahul, Rambadagalla, Malinka, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Anke, Audny, Rosenfeld, Jeffrey V., Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Antoni, Anna, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Sewalt, Charlie, Skandsen, Toril, Smielewski, Peter, Audibert, Gérard, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevens, Robert, Stewart, William, Steyerberg, Ewout W., Stocchetti, Nino, Sundström, Nina, Synnot, Anneliese, Takala, Riikka, Azouvi, Philippe, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Ao, Braden Te, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolein, Tolias, Christos, Azzolini, Maria Luisa, Trapani, Tony, Tudora, Cristina Maria, Unterberg, Andreas, Vajkoczy, Peter, Vallance, Shirley, Valeinis, Egils, Vámos, Zoltán, van der Jagt, Mathieu, Van der Steen, Gregory, Naalt, Joukje van der, Bartels, Ronald, van Dijck, Jeroen T. J. M., van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, Vyvere, Thijs Vande, van Wijk, Roel P. J., Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Barzó, Pál, Verheyden, Jan, Vespa, Paul M., Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, von Steinbüchel, Nicole, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K. W., Wiegers, Eveline, Beauvais, Romuald, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A., Zelinkova, Veronika, Ziverte, Agate, Beer, Ronny, Zoerle, Tommaso, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Lozano, Guillermo Carbayo, Carbonara, Marco, Cavallo, Simona, Chevallard, Giorgio, Chieregato, Arturo, Citerio, Giuseppe, Ceyisakar, Iris, Clusmann, Hans, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D., Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dark, Paul, Dawes, Helen, De Keyser, Véronique, Degos, Vincent, Corte, Francesco Della, Boogert, Hugo den, Depreitere, Bart, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L., Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubovic, Jagoš, Gomez, Pedro A., Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L., Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, „Springer' grupė, Ročka, Saulius, Tamošuitis, Tomas, Böhm, Julia K, Schaeben, Victoria, Güting, Helge, Thorn, Sophie, Schöchl, Herbert, Zipperle, Johanne, Grottke, Oliver, Maegele, Marc (CENTER-TBI Participants and Investigators), Beretta, L, Apollo - University of Cambridge Repository, Böhm, J, Schaeben, V, Schäfer, N, Güting, H, Lefering, R, Thorn, S, Schöchl, H, Zipperle, J, Grottke, O, Rossaint, R, Stanworth, S, Curry, N, Maegele, M, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, M, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Ceyisakar, I, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Čović, A, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, Dawes, H, De Keyser, V, Degos, V, Corte, F, Boogert, H, Depreitere, B, Đilvesi, Đ, Dixit, A, Donoghue, E, Dreier, J, Dulière, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Section Neuropsychology, and RS: FPN NPPP I

Subjects
Thrombin generation, THROMBIN ACTIVATABLE FIBRINOLYSIS, CENTER-TBI, HEMORRHAGIC PROGRESSION, Progressive intracranial hemorrhage, Critical Care and Intensive Care Medicine, Traumatic brain injury, Coagulopathy, Fibrin monomers, Brain Injuries, Traumatic, Humans, Prospective Studies, coagulopathy, fibrin monomers, progressive intracranial hemorrhage, thrombin generation, traumatic brain injury, Traumatic/epidemiology, HYPOPERFUSION, Brain Injuries, Traumatic/epidemiology, Thrombin, INHIBITOR, PATHWAYS, Plasminogen, CARE, Blood Coagulation Disorders, Fibrin monomer, Brain Injuries, Neurology (clinical), Protein C
Abstract

Neurocritical care 36(3), 927-941 (2022). doi:10.1007/s12028-021-01400-3, Published by Springer, New York, NY

Published
2022

42. Using Cg05575921 methylation to predict lung cancer risk: a potentially bias-free precision epigenetics approach

Author

Rob Philibert, Kelsey Dawes, Joanna Moody, Richard Hoffman, Jessica Sieren, and Jeffrey Long

Subjects
Male, Cancer Research, Lung Neoplasms, Smoking, Humans, Female, DNA Methylation, Lung, Molecular Biology, United States, Early Detection of Cancer, Epigenesis, Genetic
Abstract

The decision to engage in lung cancer screening (LCS) necessitates weighing benefits versus harms. Previously, clinicians in the United States have used the PLCOM

Published
2022

43. Validity of sagittal thoracolumbar curvature measurement using a non-radiographic surface topography method

Author

Erin Hannink, Helen Dawes, Thomas M. L. Shannon, and Karen L. Barker

Subjects
Adult, Male, Radiography, Cross-Sectional Studies, Lumbar Vertebrae, Humans, Reproducibility of Results, Female, Orthopedics and Sports Medicine, Kyphosis
Abstract

Purpose To estimate the criterion validity of sagittal thoracolumbar spine measurement using a surface topography method in a clinical population against the gold standard and to estimate concurrent validity against two non-radiographic clinical tools. Methods In this cross-sectional validity study, thoracolumbar curvature was measured in adults with spinal conditions recruited from a specialist orthopaedic hospital. A surface topography method using a Kinect sensor was compared to three other measurement methods: spinal radiograph (gold standard), flexicurve and digital inclinometer. Correlation coefficients and agreement between the measurement tools were analysed. Results Twenty-nine participants (79% female) were included in criterion validity analyses and 38 (76% female) in concurrent validity analyses. The surface topography method was moderately correlated with the radiograph (r = .70, p r = .32, p = .89). The surface topography method was highly correlated with the flexicurve (rs = .91, p r = .82, p r = .74, p r = .74, p Conclusions The surface topography method showed moderate correlation and agreement in thoracic spine with the radiograph (criterion validity) and high correlation with the flexicurve and digital inclinometer (concurrent validity). Compared with other non-radiographic tools, this surface topography method displayed similar criterion validity for kyphosis curvature measurement.

Published
2022

44. Differences in Aggression and Alcohol Use among Youth with Varying Levels of Victimization and Popularity Status

Author

Sarah T. Malamut, Molly Dawes, Tessa A. M. Lansu, Yvonne van den Berg, and Antonius H. N. Cillessen

Subjects
Male, Adolescent, Alcohol Drinking, Social Psychology, Bullying, Social Development, Peer Group, Education, Aggression, Developmental and Educational Psychology, Humans, Female, Crime Victims, Social Sciences (miscellaneous)
Abstract

Contains fulltext : 251472.pdf (Publisher’s version ) (Open Access) Awareness that high-status adolescents can be targets of aggression has grown in recent years. However, questions remain about the associations of the confluence of victimization and popularity with adjustment. The current study fills this gap by examining the joint and unique effects of victimization and popularity on aggression and alcohol use. Participants were 804 Dutch adolescents (50.2% boys, Mage = 13.65) who were followed for one year. High-status victims were more aggressive and drank more alcohol than lower-status victims. High-status victims were also more proactively and indirectly aggressive and self-reported more bullying than high-status non-victims. Thus, the findings demonstrated a conjoined risk of victimization and popularity for some types of aggression. 12 p.

Published
2022

45. International society of sports nutrition position stand: tactical athlete nutrition

Author

Drew E. Gonzalez, Matthew J. McAllister, Hunter S. Waldman, Arny A. Ferrando, Jill Joyce, Nicholas D. Barringer, J. Jay Dawes, Adam J. Kieffer, Travis Harvey, Chad M. Kerksick, Jeffrey R. Stout, Tim N. Ziegenfuss, Annette Zapp, Jamie L. Tartar, Jeffery L. Heileson, Trisha A. VanDusseldorp, Douglas S. Kalman, Bill I. Campbell, Jose Antonio, and Richard B. Kreider

Subjects
Nutrition and Dietetics, Athletes, Sports Nutritional Sciences, Nutritional Requirements, Humans, Energy Intake, Exercise, Diet, Food Science
Abstract

This position stand aims to provide an evidence-based summary of the energy and nutritional demands of tactical athletes to promote optimal health and performance while keeping in mind the unique challenges faced due to work schedules, job demands, and austere environments. After a critical analysis of the literature, the following nutritional guidelines represent the position of the International Society of Sports Nutrition (ISSN).Nutritional considerations should include the provision and timing of adequate calories, macronutrients, and fluid to meet daily needs as well as strategic nutritional supplementation to improve physical, cognitive, and occupational performance outcomes; reduce risk of injury, obesity, and cardiometabolic disease; reduce the potential for a fatal mistake; and promote occupational readiness.Energy demands should be met by utilizing the Military Dietary Reference Intakes (MDRIs) established and codified in Army Regulation 40-25. Although research is somewhat limited, military personnel may also benefit from caffeine, creatine monohydrate, essential amino acids, protein, omega-3-fatty acids, beta-alanine, and L-tyrosine supplementation, especially during high-stress conditions.Specific energy needs are unknown and may vary depending on occupation-specific tasks. It is likely the general caloric intake and macronutrient guidelines for recreational athletes or the Acceptable Macronutrient Distribution Ranges for the general healthy adult population may benefit first responders. Strategies such as implementing wellness policies, setting up supportive food environments, encouraging healthier food systems, and using community resources to offer evidence-based nutrition classes are inexpensive and potentially meaningful ways to improve physical activity and diet habits. The following provides a more detailed overview of the literature and recommendations for these populations.

Published
2022

46. Extending Research on Law Enforcement Academy Graduation and Fitness: A Research Note on Receiver Operating Characteristic Curves

Author

Robert G, Lockie, J Jay, Dawes, Joseph M, Dulla, and Robin M, Orr

Subjects
Male, Law Enforcement, ROC Curve, Physical Fitness, Exercise Test, Humans, Female, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine, General Medicine, Police, Retrospective Studies
Abstract

Lockie, RG, Dawes, JJ, Dulla, JM, and Orr, RM. Extending research on law enforcement academy graduation and fitness: A research note on receiver operating characteristic curves. J Strength Cond Res 36(7): 2018-2022, 2022-Fitness level contributes to a law enforcement recruit's ability to graduate from a training academy. However, limited research has used receiver operating characteristic (ROC) curves to ascertain whether fitness tests can accurately predict academy graduation. The investigators analyzed archival data from 311 recruits (260 males and 51 females) across 4 academy classes from 1 law enforcement agency. A robust, broad battery of fitness test data included grip strength for both hands, vertical jump, 75-yard pursuit run (75PR), 2-kg medicine ball throw, push-ups, sit-ups, arm ergometer revolutions in 60 seconds, and 20-m multistage fitness test (20MSFT) shuttles. Recruits were split into those who graduated (n = 269) or those who separated (did not complete academy; n = 42). A univariate ANOVA, with sex as a control variable, determined between-group fitness differences. Receiver operating characteristic curves were plotted for each fitness test, and the area under the curve (AUC) determined accuracy. Except for grip strength, graduated recruits were superior in all fitness tests (p0.001). The 75PR (AUC = 0.708) and 20MSFT (AUC = 0.727) had fair accuracy in predicting academy graduation. The data suggested that, ideally, fitness tests should not be used for diagnostic purposes in relation to academy graduation potential. Fitness test data can be used to provide specific feedback to at-risk recruits. These results suggest that the 75PR (change-of-direction speed) and 20MSFT (aerobic fitness) could contribute to successful graduation in law enforcement recruits. Law enforcement training staff could use this information to provide targeted training for recruits lacking in these qualities.

Published
2022

48. Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury

Author

Louis Jacob, Mélanie Cogné, Olli Tenovuo, Cecilie Røe, Nada Andelic, Marek Majdan, Jukka Ranta, Peter Ylen, Helen Dawes, Philippe Azouvi, Cecilia Åkerlund, Krisztina Amrein, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó9, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Andrew I.R. Maas, Ana M. Castaño-León, Marc Maegele, Alex Manara, Geoffrey Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Oresic, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Olav Roise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle, Molecular Neuroscience and Ageing Research (MOLAR), Centre of Excellence in Complex Disease Genetics, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, HUS Neurocenter, Neurokirurgian yksikkö, Helsinki Institute for Information Technology, Statistical and population genetics, Department of Mathematics and Statistics, Biostatistics Helsinki, Clinicum, Helsinki University Hospital Area, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Jacob, L., Cogne, M., Tenovuo, O., Roe, C., Andelic, N., Majdan, M., Ranta, J., Ylen, P., Dawes, H., Azouvi P., (CENTER-TBI Participants and Investigators), Beretta, Luigi, Jacob, L, Cogne, M, Tenovuo, O, Roe, C, Andelic, N, Majdan, M, Ranta, J, Ylen, P, Dawes, H, Azouvi, P, Akerlund, C, Amrein, K, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azzolini, M, Bartels, R, Barzo9, P, Beauvais, R, Beer, R, Bellander, B, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Buki, A, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, M, Cameron, P, Carbayo Lozano, G, Carbonara, M, Cavallo, S, Chevallard, G, Chieregato, A, Citerio, G, Ceyisakar, I, Clusmann, H, Coburn, M, Coles, J, Cooper, J, Correia, M, Covic, A, Curry, N, Czeiter, E, Czosnyka, M, Dahyot-Fizelier, C, Dark, P, De Keyser, V, Degos, V, Della Corte, F, den Boogert, H, Depreitere, B, Dilvesi, D, Dixit, A, Donoghue, E, Dreier, J, Duliere, G, Ercole, A, Esser, P, Ezer, E, Fabricius, M, Feigin, V, Foks, K, Frisvold, S, Furmanov, A, Gagliardo, P, Galanaud, D, Gantner, D, Gao, G, George, P, Ghuysen, A, Giga, L, Glocker, B, Golubovic, J, Gomez, P, Gratz, J, Gravesteijn, B, Grossi, F, Gruen, R, Gupta, D, Haagsma, J, Haitsma, I, Helbok, R, Helseth, E, Horton, L, Huijben, J, Hutchinson, P, Jacobs, B, Jankowski, S, Jarrett, M, Jiang, J, Johnson, F, Jones, K, Karan, M, Kolias, A, Kompanje, E, Kondziella, D, Koraropoulos, E, Koskinen, L, Kovacs, N, Kowark, A, Lagares, A, Lanyon, L, Laureys, S, Lecky, F, Ledoux, D, Lefering, R, Legrand, V, Lejeune, A, Levi, L, Lightfoot, R, Lingsma, H, Maas, A, Castano-Leon, A, Maegele, M, Manara, A, Manley, G, Martino, C, Marechal, H, Mattern, J, Mcmahon, C, Melegh, B, Menon, D, Menovsky, T, Mikolic, A, Misset, B, Muraleedharan, V, Murray, L, Negru, A, Nelson, D, Newcombe, V, Nieboer, D, Nyiradi, J, Olubukola, O, Oresic, M, Ortolano, F, Palotie, A, Parizel, P, Payen, J, Perera, N, Perlbarg, V, Persona, P, Peul, W, Piippo-Karjalainen, A, Pirinen, M, Ples, H, Polinder, S, Pomposo, I, Posti, J, Puybasset, L, Radoi, A, Ragauskas, A, Raj, R, Rambadagalla, M, Rhodes, J, Richardson, S, Richter, S, Ripatti, S, Rocka, S, Roise, O, Rosand, J, Rosenfeld, J, Rosenlund, C, Rosenthal, G, Rossaint, R, Rossi, S, Rueckert, D, Rusnak, M, Sahuquillo, J, Sakowitz, O, Sanchez-Porras, R, Sandor, J, Schafer, N, Schmidt, S, Schoechl, H, Schoonman, G, Schou, R, Schwendenwein, E, Sewalt, C, Skandsen, T, Smielewski, P, Sorinola, A, Stamatakis, E, Stanworth, S, Stevens, R, Stewart, W, Steyerberg, E, Stocchetti, N, Sundstrom, N, Synnot, A, Takala, R, Tamas, V, Tamosuitis, T, Taylor, M, Te Ao, B, Theadom, A, Thomas, M, Tibboel, D, Timmers, M, Tolias, C, Trapani, T, Tudora, C, Vajkoczy, P, Vallance, S, Valeinis, E, Vamos, Z, van der Jagt, M, Van der Steen, G, van der Naalt, J, van Dijck, J, van Essen, T, Van Hecke, W, van Heugten, C, Van Praag, D, Vande Vyvere, T, van Wijk, R, Vargiolu, A, Vega, E, Velt, K, Verheyden, J, Vespa, P, Vik, A, Vilcinis, R, Volovici, V, von Steinbuchel, N, Voormolen, D, Vulekovic, P, Wang, K, Wiegers, E, Williams, G, Wilson, L, Winzeck, S, Wolf, S, Yang, Z, Younsi, A, Zeiler, F, Zelinkova, V, Ziverte, A, Zoerle, T, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Oslo University Hospital [Oslo], Oxford Brookes University, European Commission, EC: 602150, The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Data used in preparation of this article were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC Grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA), and from Integra LifeSciences Corporation (USA). Data for the CENTER-TBI study were collected through the Quesgen e-CRF (Quesgen Systems Inc, USA), hosted on the INCF platform and extracted via the INCF Neurobot tool (INCF, Sweden). The funder had no role in the study design, collection, analysis, and interpretation of the data, writing of the report, and the decision to submit the article for publication., European Project: 602150,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,CENTER-TBI(2013), Section Neuropsychology, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: FPN NPPP I, and Psychiatrie & Neuropsychologie

Subjects
Male, 030506 rehabilitation, Neurology, predictive factors, IMPACT, medicine.medical_treatment, CENTER-TBI, Health Services Accessibility, 3124 Neurology and psychiatry, predictive factor, Injury Severity Score, 0302 clinical medicine, Brain Injuries, Traumatic, Epidemiology, EPIDEMIOLOGY, Prospective Studies, rehabilitation, OUTCOMES, Rehabilitation, traumatic brain injury, Neurological Rehabilitation, General Medicine, Middle Aged, RECOVERY, Prognosis, 3. Good health, Hospitalization, Europe, Educational Status, international prospective study, Female, HEALTH, 0305 other medical science, Adult, Employment, medicine.medical_specialty, Traumatic brain injury, 03 medical and health sciences, Sex Factors, medicine, Humans, Glasgow Coma Scale, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, MORTALITY, 3112 Neurosciences, PATHWAYS, CARE, medicine.disease, Multicenter study, Emergency medicine, MODERATE, business, 030217 neurology & neurosurgery
Abstract

BackgroundAlthough rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care.ObjectiveTherefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI.MethodsData from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge.ResultsIn the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24).ConclusionsBased on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.

Published
2020

49. Effect of frailty on 6-month outcome after traumatic brain injury: a multicentre cohort study with external validation

Author

Stefania Galimberti, Francesca Graziano, Andrew I R Maas, Giulia Isernia, Fiona Lecky, Sonia Jain, Xiaoying Sun, Raquel C Gardner, Sabrina R Taylor, Amy J Markowitz, Geoffrey T Manley, Maria Grazia Valsecchi, Giuseppe Bellelli, Giuseppe Citerio, Cecilia Ackerlund, Hadie Adams, Krisztina Amrein, Nada Andelic, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo-Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Andras Buki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Ana M. Castaño-León, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Hans Clusmann, Mark Steven Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Covic, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot-Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Francesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens Dreier, Guy-Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubovic, Pedro A. Gomez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Ji-yao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin Kompanje, Daniel Kondziella, Lars-Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Didier Ledoux, Rolf Lefering, Valerie Legrand, Aurelie Lejeune, Leon Levi, Roger Lightfoot, Hester Lingsma, Marc Maegele, Marek Majdan, Alex Manara, Hugues Maréchal, Costanza Martino, Julia Mattern, Charles McFadyen, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolic, Benoit Misset, Visakh Muraleedharan, Lynnette Murray, Ancuta Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Matej Oresic, Fabrizio Ortolano, Olubukola Otesile, Aarno Palotie, Paul M. Parizel, Jean-François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco Peul, Anna Piippo-Karjalainen, Matti Pirinen, Dana Pisica, Horia Ples, Suzanne Polinder, Inigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Radoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Veronika Rehorčíková, Isabel Retel Helmrich, Jonathan Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Rocka, Cecilie Roe, Olav Roise, Jeffrey Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusnák, Juan Sahuquillo, Oliver Sakowitz, Renan Sanchez-Porras, Janos Sandor, Nadine Schäfer, Silke Schmidt, Herbert Schoechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Ranjit D. Singh, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel Stamatakis, Simon Stanworth, Robert Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamosuitis, Mark Steven Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolijn Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Egils Valeinis, Shirley Vallance, Zoltán Vámos, Mathieu van der Jagt, Joukje van der Naalt, Gregory Van der Steen, Jeroen T.J.M. van Dijck, Inge A. van Erp, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Ernest van Veen, Roel van Wijk, Thijs Vande Vyvere, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul M. Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Peter Vulekovic, Kevin K.W. Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. 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I. R., Isernia, G., Lecky, F., Jain, S., Sun, X., Gardner, R. C., Taylor, S. R., Markowitz, A. J., Manley, G. T., Valsecchi, M. G., Bellelli, G., Citerio, G., Ackerlund, C., Adams, H., Amrein, K., Andelic, N., Andreassen, L., Anke, A., Antoni, A., Audibert, G., Azouvi, P., Azzolini, M. L., Bartels, R., Barzo, P., Beauvais, R., Beer, R., Bellander, B. -M., Belli, A., Benali, H., Berardino, M., Beretta, L., Blaabjerg, M., Bragge, P., Brazinova, A., Brinck, V., Brooker, J., Brorsson, C., Buki, A., Bullinger, M., Cabeleira, M., Caccioppola, A., Calappi, E., Calvi, M. R., Cameron, P., Carbayo Lozano, G., Carbonara, M., Castano-Leon, A. M., Cavallo, S., Chevallard, G., Chieregato, A., Clusmann, H., Coburn, M. S., Coles, J., Cooper, J. 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A., Van Hecke, W., van Heugten, C., Van Praag, D., van Veen, E., van Wijk, R., Vande Vyvere, T., Vargiolu, A., Vega, E., Velt, K., Verheyden, J., Vespa, P. M., Vik, A., Vilcinis, R., Volovici, V., von Steinbuchel, N., Voormolen, D., Vulekovic, P., Wang, K. K. W., Wiegers, E., Williams, G., Wilson, L., Wolf, S., Yang, Z., Ylen, P., Younsi, A., Zeiler, F. A., Ziverte, A., Zoerle, T., Adeoye, O., Badjatia, N., Barber, J., Bergin, M., Boase, K., Bodien, Y., Chesnut, R., Corrigan, J., Crawford, K., Diaz-Arrastia, R., Dikmen, S., Duhaime, A. -C., Ellenbogen, R., Feeser, V., Ferguson, A. R., Foreman, B., Gaudette, E., Giacino, J., Gonzalez, L., Gopinath, S., Grandhi, R., Gullapalli, R., Hemphill, C., Hotz, G., Huie, R., Jha, R., Keene, C. D., Kitagawa, R., Korley, F., Kramer, J., Kreitzer, N., Levin, H., Lindsell, C., Machamer, J., Madden, C., Martin, A., Mcallister, T., Mccrea, M., Merchant, R., Mukherjee, P., Nelson, L., Ngwenya, L. 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Subjects
Male, Traumatic/therapy, Frailty, Brain Injuries, Traumatic/therapy, traumatic brain injury, Reproducibility of Results, Middle Aged, Cohort Studies, Brain Injuries, Brain Injuries, Traumatic, outcome, Humans, Glasgow Coma Scale, Neurology (clinical), Human medicine, Prospective Studies, Aged
Abstract

Background: Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good performance to predict clinical outcomes. However, each is specific to a particular clinical context. We aimed to develop a frailty index to predict 6-month outcomes in patients after a traumatic brain injury. Methods: A cumulative deficit approach was used to create a novel frailty index based on 30 items dealing with disease states, current medications, and laboratory values derived from data available from CENTER-TBI, a prospective, longitudinal observational study of patients with traumatic brain injury presenting within 24 h of injury and admitted to a ward or an intensive care unit at 65 centres in Europe between Dec 19, 2014, and Dec 17, 2017. From the individual cumulative CENTER-TBI frailty index (range 0–30), we obtained a standardised value (range 0–1), with high scores indicating higher levels of frailty. The effect of frailty on 6-month outcome evaluated with the extended Glasgow Outcome Scale (GOSE) was assessed through a proportional odds logistic model adjusted for known outcome predictors. An unfavourable outcome was defined as death or severe disability (GOSE score ≤4). External validation was performed on data from TRACK-TBI, a prospective observational study co-designed with CENTER-TBI, which enrolled patients with traumatic brain injury at 18 level I trauma centres in the USA from Feb 26, 2014, to July 27, 2018. CENTER-TBI is registered with ClinicalTrials.gov, NCT02210221; TRACK-TBI is registered at ClinicalTrials.gov, NCT02119182. Findings: 2993 participants (median age was 51 years [IQR 30–67], 2058 [69%] were men) were included in this analysis. The overall median CENTER-TBI frailty index score was 0·07 (IQR 0·03–0·15), with a median score of 0·17 (0·08–0·27) in older adults (aged ≥65 years). The CENTER-TBI frailty index score was significantly associated with the probability of an increasingly unfavourable outcome (cumulative odds ratio [OR] 1·03, 95% CI 1·02–1·04; p

Published
2022

50. Outcomes of importance to children and young adults with cerebral palsy, their parents and health professionals following lower limb orthopaedic surgery: A qualitative study to inform a Core Outcome Set

Author

Hajar Almoajil, Francine Toye, Helen Dawes, Jo Pierce, Andrew Meaney, Aziz Baklouti, Lara Poverini, Sally Hopewell, and Tim Theologis

Subjects
Parents, Young Adult, Adolescent, Lower Extremity, Cerebral Palsy, Outcome Assessment, Health Care, Quality of Life, Public Health, Environmental and Occupational Health, Humans, Orthopedic Procedures, Child
Abstract

Introduction Although several outcomes are commonly measured to assess the effect of surgery for young people with cerebral palsy (CP), these are selected mainly by health professionals and researchers. Including the perspectives of a broader range of stakeholders is an essential step towards determining important outcomes for assessment. This qualitative study involves the development of a core outcome set (COS) for lower limb orthopaedic surgery for ambulant children with CP. Objective This study aimed to identify outcomes that matter to children and young people with CP, their parents and healthcare professionals following lower limb orthopaedic surgery. Methods Semi-structured interviews were conducted with 10 healthcare professionals, 10 children and young people with CP and 8 parents. Interview data were analysed by content analysis supported by the International Classification of Functioning, Disability and Health (ICF-CY) supplemented by thematic analysis. Findings Thirty-one outcomes were identified in total, which were linked to eleven second-level ICF-CY categories. There were differences between stakeholder groups in preferences and expectations from surgical outcomes. Healthcare professionals and children with their parents identified 31 and 25 outcomes, respectively. Health outcomes valued by participants were lower limb alignment and symmetry, flexibility and muscle strength, mental health, fatigue, pain, function in life, mobility, participation, being independent, quality of life and adverse events. Compared to previous published trials, 10 new outcomes were revealed by this study. Conclusion The researchers identified outcomes that are important to all stakeholders following lower limb orthopaedic surgery for ambulant CP. Including these outcomes in future studies would promote patient-centred care for children and young adults with CP. Findings will be used to inform an international Delphi survey and develop a COS in this field. Patient and Public Contribution This study was informed by an advisory group including a young adult with CP and a parent of a child with CP. This group engaged in the design of the study and the information material to support the interview (information sheet and interview topic guide).

Published
2022

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