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Introduction The use of an electronic health record may create unanticipated consequences for emergency care delivery. We sought to describe emergency department nursing task distribution and the use of the electronic health record. Methods This was a prospective observational study of nurses in the emergency department using a time-and-motion methodology. Three trained research assistants conducted 1:1 observations between March and September 2019. Nurse tasks were classified into 6 established categories: electronic health record, direct/indirect patient care, communication, personal time, and other. Nurses’ perceived workload was assessed using the National Aeronautics and Space Administration (NASA) Task Load Index. Results Twenty-three observations were conducted over 46 hours. Overall, nurses spent 27% of their time on electronic health record tasks, 25% on direct patient care, 17% on personal time, 15% on indirect patient care, and 6% on communication. During morning (7 am -12 pm ) and afternoon shifts (12 pm -3 pm ), the use of the health record was the most commonly performed task, whereas indirect patient care was the task most performed during evening shifts (3 pm -12 pm ). Using the National Aeronautics and Space Administration (NASA) Task Load Index, nurses reported an increase in mental demand and effort during afternoon shifts compared with morning shifts. Discussion We observed that emergency nurses spent more time using the electronic health record as compared to other tasks. Increased usability of the electronic health record, particularly during high occupancy periods, may be a target for improvement.

Assess effects of an obesity prevention program promoting eating self-regulation and healthy preferences in Hispanic preschool children.Randomized controlled trial with pretest, posttest, 6- and 12-month assessments. Fourteen waves, each lasting 7 weeks.Families recruited from Head Start across 2 sites.Two hundred fifty-five families randomized into prevention (n = 136) or control (n = 119).Prevention received curriculum; control received no curriculum.Feeding knowledge/practices/styles (parent); body mass index percentile, eating self-regulation, trying new foods, and fruit/vegetable consumption (child).Multilevel analyses for nested data (time points within families; families within waves) and multinomial regression.Program increased mothers' repeated presentation of new foods (P0.05), measured portion sizes (P0.05), child involvement in food preparation (P0.001), feeding responsiveness (P0.001), knowledge of best feeding practices (P0.001), and feeding efficacy (P0.05); reduced feeding misconceptions (P0.01) and uninvolved feeding (P0.01). Effects on child eating behavior were minimal. At 12 months, children in the prevention group were less likely to have overweight (P0.05) or obesity (P0.05).Program effects emphasize the importance of feeding approaches in reducing childhood obesity.

Cytochrome P450 2D6 (CYP2D6) copy number (CN) variation affects the metabolism of numerous prescribed drugs. Sequence variation within primer or probe target regions of hydrolysis probe CN assays can generate false-positive calls for CN loss. Furthermore, CYP2D6–CYP2D7 hybrids and gene conversions can cause difficult to interpret discordant CN calls. The identification of haplotypes with CN variations and structural arrangements is important to predict phenotype accurately. During clinical testing with hydrolysis probe assays targeting three CYP2D6 regions (intron 2, intron 6, and exon 9), samples with haplotypes causing inconsistent CN calls were identified. To resolve these cases, next-generation sequencing and allele-specific Sanger sequencing was performed. Sequence analysis of 16 samples, all but one from subjects of African descent, identified six novel suballeles containing single-nucleotide polymorphisms, which cause false-positive calls for CN loss in introns 2 and 6. Five samples with an exon 9 CN loss contained CYP2D6/CYP2D7 hybrids (∗13 or ∗36) and one sample was found to have a novel haplotype, CYP2D6∗141. Interestingly, CYP2D6∗141 contains a CYP2D7-derived exon 9 conversion and core single-nucleotide polymorphisms that are otherwise found in CYP2D6∗17 and ∗27. Although these variants are rare, they can cause inconsistent CN calls that typically are reported as no calls or indeterminant, and thus may deprive patients, particularly those of African descent, from taking full benefit of pharmacogenetic testing.

Objective Compared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS). Methods Across two sites, 37 children with ADHD and 45 TD children, ages 8–12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models. Results In both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms. Conclusions In children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement. Significance Evaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.

Background : Damage control surgery is the practice of delaying definitive management of traumatic injuries by controlling hemorrhage in the operating room and restoring normal physiology in the intensive care unit prior to definitive therapy. Presently, damage control or “abbreviated” laparotomy is used extensively for abdominal trauma in an unstable patient. The application of a damage control approach in thoracic trauma is less established and there is a paucity of literature supporting or refuting this practice. We aimed to systematically review the current data on damage control thoracotomy (DCT), to identify gaps in the literature and techniques in temporary closure. Methods : An electronic literature search of Pubmed, MEDLINE, and the Cochrane Database of Collected Reviews from 1972-2018 was performed using the keywords “thoracic,” “damage control,” and “thoracotomy.” Studies were included if they reported the use of DCT following thoracic trauma and included survival as an outcome. Results : Of 723 studies, seven met inclusion criteria for a total of a 130 DCT operations. Gauze packing with temporary closure of the skin with suture was the most frequently reported form of closure. The overall survival rate for the seven studies was 67%. Survival rates ranged from 42-77%. Average injury severity score was 30, and 64% of injuries were penetrating in nature. The most common complications included infections (57%; pneumonia, empyema, wound infection, bacteremia), respiratory failure (21%), ARDS (8%), and renal failure (18%). Conclusion : DCT may be associated with improved survival in the critically injured patient population. Delaying definitive operation by temporarily closing the thorax in order to allow time to restore normal physiology may be considered as a strategy in the unstable thoracic trauma patient population. The impact an open chest has on respiratory physiology remains inconclusive as well as best mechanisms of temporary closure. Multi-center studies are required to elucidate these important questions.

Background School-environments are thought to be strong influences of behavioral choices. There is limited research available on the role of physical activity (PA) and school success among children with special health care needs (CSHCN). The purpose of this study was to explore differences in PA among CSHCN and non-CSHCN and how the school success index is related to PA in both groups. Methods Data were taken from new version of the National Survey of Children's Health (NSCH), which consolidated questions from the previous NSCH and the National Survey of Children with Special Health Care Needs (NS-CSHCN). Chi-square and logistic regression analyses were employed to examine group differences. Results There were significant differences among both subgroups, although most school-aged children did not meet recommended PA guidelines. Chi-squared analyses indicated; school engagement and the parent's perception of child safety at school were associated with the likelihood of meeting PA guidelines. Logistic regression analyses showed that the odds of meeting PA guidelines were associated with the school success index. Conclusions Comprehensive school health programs should focus on PA both subgroups. School health educators should continue to advocate for safe and structured extracurricular activities to improve the child and adolescent's engagement and overall well-being.

GABA is the primary inhibitory neurotransmitter in the brain, and is essential to the balance of cortical excitation and inhibition. Reductions in GABA are proposed to result in an overly excitatory cortex that may cause, or contribute to, symptoms of autism spectrum disorder (ASD). This study employed a cross-sectional design to explore GABA+ differences in ASD and the impact of age, comparing 4-12 year olds with ASD (N = 24) to typically developing children (N = 35). GABA+ concentration was measured using edited magnetic resonance spectroscopy in the left parietal lobe. This study used a mixed model to investigate group differences between children with ASD and typically developing children. There was a significant difference in GABA+ levels between the groups, a significant effect of age and interaction between age and diagnostic group. The ASD group showed an association between GABA+ and age, with GABA+ levels gradually increasing with age (r = 0.59, p = 0.003). Typically developing children did not show age-related change in GABA+ concentration (r = 0.09, p = 0.60). By the age of 9, children with ASD showed GABA+ levels that were comparable to their typically developing peers. This study suggests that children with ASD have initially lower levels of GABA+ in the left parietal lobe compared to typically developing children, and that these initially lower levels of GABA+ increase with age in ASD within this region. It is suggested that this developmental shift of GABA+ levels within the left parietal lobe provides a possible explanation for the previously found reductions in childhood that does not persist in adults. LAY SUMMARY: This study measured levels of GABA in the left parietal lobe using magnetic resonance spectroscopy in children with ASD and typically developing children. GABA levels were initially lower in the ASD group, and increased with age, while GABA did not change with age in the typically developing group. This suggests that alterations in GABA signaling may be associated with ASD in childhood. Autism Res 2021, 14: 859-872. © 2021 International Society for Autism Research, Wiley Periodicals LLC.

BACKGROUND: Extreme thrombocytosis (EXT, platelet count >1000 × 10(3)/μl) is an uncommon but potentially clinically significant finding. Primary EXT in the setting of myeloproliferative disorders is linked to thrombotic and/or bleeding complications more frequently than secondary EXT, which typically occurs in reaction to infection, inflammation, or iron deficiency. However, comorbidities have been reported in adults with secondary EXT. Clinical implications of EXT in children are not well-defined, as prior studies targeted small and/or specialized pediatric populations. OBJECTIVES: Our objective was to determine etiologies and sequelae of extreme thrombocytosis in a hospitalized general pediatric patient population. PATIENTS AND METHODS: We retrospectively analyzed EXT cases from a single-center pediatric cohort of ~80,000 patients over 8 years. RESULTS: Virtually all cases (99.8%) were secondary in nature, and most were multifactorial. Many cases of EXT occurred in children under 2 years old (47%) and/or during critical illness (55%). No thrombotic or bleeding events directly resulted from EXT, confirming a paucity of clinical complications associated with EXT in pediatric patients. There were indications that neonatal hematopoiesis and individual genetic variation influenced some cases, in addition to certain diagnoses (e.g., sickle cell anemia) and clinical contexts (e.g., asplenia). CONCLUSION: Our findings confirm that thrombotic events related to EXT are rare in pediatric patients, which can inform the use of empiric anti-platelet therapy.

Biodiversity is being lost at an alarming rate, but the rate of this loss is likely to be underestimated as a result of a deficit in taxonomic knowledge (i.e. the Linnean shortfall). This knowledge gap is more extensive for morphologically indistinct taxa. The advancement of molecular techniques and delimitation methods has facilitated the identification of such cryptic species, but a majority of these taxa remain undescribed. To investigate the effects of taxonomic uncertainty on understanding of biodiversity, we applied the general lineage concept of species to an amphipod species complex, the Gammaruslacustris lineage that occupies springs of the northern Chihuahuan Desert, which is emerging in contemporary times. We investigated species boundaries using a validation-based approach and examined genetic structure of the lineage using a suite of microsatellite markers to identify independently evolving metapopulations. Our results show that each spring contains a genetically distinct population that is geographically isolated from other springs, suggesting evolutionary independence and status as separate species. Additionally, we observed subtle interspecific morphological variation among the putative species. We used multiple lines of evidence to formally describe four new species (Gammarus langi sp. nov., G. percalacustris sp. nov., G. colei sp. nov. and G. malpaisensis sp. nov.) endemic to the northern Chihuahuan Desert. Cryptic speciation is likely to be high in other aquatic taxa within these ecosystems, and across arid landscapes throughout North America and elsewhere, suggesting that the magnitude of the Linnean shortfall is currently underestimated in desert springs worldwide.

Evaluators learning about developmental evaluation (DE) may struggle with the need for guidance on the concrete specifics of how to “do developmental evaluation” because of the need to tailor the use of the method to the context of the program being evaluated. Case examples in the literature provide illustrations of how others have applied this approach. This article adds to this growing body of knowledge by detailing the experience of the first year of a multiyear developmental evaluation of Complex Care Hub. This healthcare program is a hospital-at-home model where patients receive hospital-level services but sleep in their own home and receive case management as needed. The article ends with a discussion of challenges and lessons learned.

Nitric oxide synthase (NOS) inhibition with N(G)-monomethyl- l -arginine (L-NMMA) is often used to assess the role of NO in human cardiovascular function. However, the window of effect for L-NMMA on human vascular function is unknown, which is critical for designing and interpreting human-based studies. This study utilized the passive leg movement (PLM) assessment of vascular function, which is predominantly NO-mediated, in 7 young male subjects under control conditions, immediately following intra-arterial L-NMMA infusion (0.24 mg⋅dl−1⋅min−1), and at 45–60 and 90–105 min post L-NMMA infusion. The leg blood flow (LBF) and leg vascular conductance (LVC) responses to PLM, measured with Doppler ultrasound and expressed as the change from baseline to peak (ΔLBFpeak and ΔLVCpeak) and area under the curve (LBFAUC and LVCACU), were assessed. PLM-induced robust control ΔLBFpeak (1135 ± 324 ml⋅min−1) and ΔLVCpeak (10.7 ± 3.6 ml⋅min−1⋅mmHg−1) responses that were significantly attenuated (704 ± 196 ml⋅min−1 and 6.7 ± 2 ml⋅min−1⋅mmHg−1) immediately following L-NMMA infusion. Likewise, control condition PLM ΔLBFAUC (455 ± 202 ml) and ΔLVCAUC (4.0 ± 1.4 ml⋅mmHg−1) were significantly attenuated (141 ± 130 ml and 1.3 ± 1.2 ml⋅mmHg−1) immediately following L-NMMA infusion. However, by 45–60 min post L-NMMA infusion all PLM variables were not significantly different from control, and this was still the case at 90–105 min post L-NMMA infusion. These findings reveal that the potent reduction in NO bioavailability afforded by NOS inhibition with L-NMMA has a window of effect of less than 45–60 min in the human vasculature. These data are particularly important for the commonly employed approach of pharmacologically inhibiting NOS with L-NMMA in the human vasculature.

The most stressful phase of deployment for military families with young children is pre-deployment; they are often overlooked in family preparation strategies. Failure to prepare young children may...

Supplemental Digital Content is Available in the Text. Using magnetic resonance spectroscopy in vivo, we show GABA and glutamate alterations in children aged 7 to 13 years with migraine, which are associated with migraine characteristics., Migraine is one of the top 5 most prevalent childhood diseases; however, effective treatment strategies for pediatric migraine are limited. For example, standard adult pharmaceutical therapies are less effective in children and can carry undesirable side effects. To develop more effective treatments, improved knowledge of the biology underlying pediatric migraine is necessary. One theory is that migraine results from an imbalance in cortical excitability. Magnetic resonance spectroscopy (MRS) studies show changes in GABA and glutamate levels (the primary inhibitory and excitatory neurotransmitters in the brain, respectively) in multiple brain regions in adults with migraine; however, they have yet to be assessed in children with migraine. Using MRS and GABA-edited MRS, we show that children (7-13 years) with migraine and aura had significantly lower glutamate levels in the visual cortex compared to controls, the opposite to results seen in adults. In addition, we found significant correlations between metabolite levels and migraine characteristics; higher GABA levels were associated with higher migraine burden. We also found that higher glutamate in the thalamus and higher GABA/Glx ratios in the sensorimotor cortex were associated with duration since diagnosis, i.e., having migraines longer. Lower GABA levels in the sensorimotor cortex were associated with being closer to their next migraine attack. Together, this indicates that GABA and glutamate disturbances occur early in migraine pathophysiology and emphasizes that evidence from adults with migraine cannot be immediately translated to pediatric sufferers. This highlights the need for further mechanistic studies of migraine in children, to aid in development of more effective treatments.

Objective To describe the system-wide implementation of integrated electronic prior authorization (ePA) and its impact within a centralized prior authorization (PA) department in an academic health system. Setting Prescription drugs have been among the fastest growing areas of health care and continue to advance; therefore, costs associated with medications are continually rising. Pharmacy benefit managers implement tools such as PAs in an effort to manage costs. PAs are often viewed as inconvenient and irritating by both patients and clinical staff. Practice description The pharmacy ambulatory clinical care center (PAC3), a centralized PA department, provides PA services to some clinics within the system. Since 2014, the system has worked to optimize the manual (by telephone and fax) PA process. However, it is still a time-consuming, multistep process. Practice innovation A resolution to the PA problems that health systems face is ePA, which involves processing PAs electronically through an online portal or integrated within an electronic health record. The system began the implementation process with the selection of an ePA vendor, followed by implementation within the electronic health record. Once the software was ready, the system took a phased rollout approach and implemented ePA in a few specialty and primary care clinics at a time. Evaluation An average of 24% of PAs processed by PAC3 were completed by ePA. The system saw a 25% increase in the number of PAs processed per month by 1 PA coordinator full-time equivalent. In addition, a 62% decrease in the PA turnaround time allowed patients to receive medications faster. Results Not applicable. Conclusion ePA offers several benefits to the system including decreased turnaround time. This allows patients to receive medications and start therapy earlier. The ePA process also increased efficiency, allowing PAC3 to centrally manage PAs for additional clinics, thereby decreasing the workload in the clinic.

OBJECTIVES The purpose of this study was to determine correlation and temporal association between automated pupillary measurements and intracranial pressure in pediatric patients with brain injury or encephalopathy requiring intracranial pressure monitoring. We hypothesized that abnormal pupillary measurements would precede increases in intracranial pressure. DESIGN A prospective cohort study was performed. Automated pupillometry measurements were obtained at the same frequency as the patients' neurologic assessments with concurrent measurement of intracranial pressure, for up to 72 hours. Pupillary measurements and the Neurologic Pupil index, an algorithmic score that combines measures of pupillary reactivity, were assessed for correlation with concurrent and future intracranial pressure measurements. SETTING Single-center pediatric quaternary ICU, from July 2017 to October 2018. PATIENTS Pediatric patients 18 years or younger with a diagnosis of acute brain injury or encephalopathy requiring an intracranial pressure monitor. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Twenty-eight patients were analyzed with a total of 1,171 intracranial pressure measurements. When intracranial pressure was elevated, the Neurologic Pupil index, percent change in pupillary size, constriction velocity, and dilation velocity were significantly lower than when intracranial pressure was within normal range (p < 0.001 for all). There were mild to moderate negative correlations between concurrent intracranial pressure and pupillary measurements. However, there was an inconsistent pattern of abnormal pupillary measurements preceding increases in intracranial pressure; some patients had a negative association, while others had a positive relationship or no relationship between Neurologic Pupil index and intracranial pressure. CONCLUSIONS Our data indicate automated assessments of pupillary reactivity inversely correlate with intracranial pressure, demonstrating that pupillary reactivity decreases as intracranial pressure increases. However, a temporal association in which abnormal pupillary measurements precede increases in intracranial pressure was not consistently observed. This work contributes to limited data available regarding automated pupillometry in neurocritically ill patients, and the even more restricted subset available in pediatrics.

Objective: Despite increasing interest in the neurobiological effects of concussion in youth, a paucity of information is available regarding outcomes long after injury. The objective of this study was to determine the association between a history of concussion and the putative neuronal marker N-acetyl-aspartate (NAA) in the dorsolateral prefrontal cortex (DLPFC) in youth. Setting: Outpatient clinic in a children's hospital. Participants: Youth with concussion (N = 35, mean = 2.63, SD = 1.07 years postinjury) and youth with a nonconcussive orthopedic injury (N = 17) participated. Design: A cross-sectional proton magnetic resonance spectroscopy (H-MRS) study. Main Measures: The primary outcome measure was NAA concentration in the right and left DLPFCs. Results: We observed lower levels of NAA in the right DLPFC in youth with past concussion (F = 3.31, df = 4,51, P =.018) than in orthopedic controls but not in the left DLPFC (F = 2.04, df = 4,51, P =.105). The effect of lower NAA concentrations in the right DLPFC was primarily driven by youth with a single prior concussion versus those with multiple concussions. NAA in the left DLPFC, but not in right DLPFC, was associated with worse emotional symptoms in youth with concussion. Conclusion: The presence of lower levels of DLPFC NAA suggests potential association of concussion in youth, although further investigation is needed, given that the result is driven by those with a single (and not multiple) concussion. Exploration of applying MRS in other brain regions is also warranted.

The complex topography, climate, and geological history of Western North America have shaped contemporary patterns of biodiversity and species distributions in the region. Pacific martens (Martes caurina) are distributed along the northern Pacific Coast of North America with disjunct populations found throughout the Northwestern Forested Mountains and Marine West Coast Forest ecoregions of the West Coast. Martes in this region have been classified into subspecies; however, the subspecific designation has been extensively debated. In this study, we use genomic data to delineate conservation units of Pacific marten in the Sierra-Cascade-Coastal montane belt in the western United States. We analyzed the mitochondrial genome for 94 individuals to evaluate the spatial distribution and divergence times of major lineages. We further genotyped 401 individuals at 13 microsatellite loci to investigate major patterns of population structure. Both nuclear and mitochondrial DNA suggest substantial genetic substructure concordant with historical subspecies designations. Our results revealed that the region contains 2 distinct mitochondrial lineages: a Cascades/Sierra lineage that diverged from the Cascades/coastal lineage 2.23 (1.48–3.14 mya), consistent with orogeny of the Cascade Mountain chain. Interestingly, Pacific Martes share phylogeographic patterns similar with other sympatric taxa, suggesting that the complex geological history has shaped the biota of this region. The information is critical for conservation and management efforts, and further investigation of adaptive diversity is warranted following appropriate revision of conservation management designations.

Summary Single-cell DNA template strand sequencing (Strand-seq) enables chromosome length haplotype phasing, construction of phased assemblies, mapping sister-chromatid exchange events and structural variant discovery. The initial quality control of potentially thousands of single-cell libraries is still done manually by domain experts. ASHLEYS automates this tedious task, delivers near-expert performance and labels even large datasets in seconds. Availability and implementation github.com/friendsofstrandseq/ashleys-qc, MIT license. Supplementary information Supplementary data are available at Bioinformatics online.

Drug poisoning deaths involving opioids have increased exponentially in the United States. Post-overdose outreach to patients in the emergency room (ER) is a promising strategy for increasing uptake of medication assisted treatment and reducing subsequent overdose. We conducted a mixed methods study to investigate the feasibility and acceptability of a mobile recovery outreach team (MROT) program for opioid overdose patients presenting in Nevada's ERs, which was funded by the SAMHSA Opioid State Targeted Response (STR) grant. We interviewed 25 ER staff using quantitative questions informed by Diffusion of Innovation (DOI) theory and qualitative questions regarding their experiences caring for overdose patients, perceived benefits, and concerns about the MROT program. Respondents expressed strong support and enthusiasm for the program, identified advantages of the program relative to standard of care, highlighted logistical issues that must be addressed prior to implementation, and illustrated how the MROT program is compatible with their personal and professional values. Our results suggest that the STR-funded MROT program could reduce burden and stress among ER staff and improve patient outcomes, but must be informed by formative research that addresses issues of logistical complexity and cultural compatibility.

SUMMARY: Salmonella infection in humans from poultry meat and eggs can lead to symptoms including diarrhea, fever, and vomiting. Salmonella can be inhibited by acidifiers, which alter the bacterial cell membrane by disrupting bacterial nutrient transport and energy metabolism. This study analyzes the effects of a commercial acidifier, containing formic, propionic, and acetic acids combined with cinnamaldehyde, on Salmonella infection in laying hens. A total of 384 one-day-old layer chicks were supplemented with or without acidifier from day of hatch through 28 wk of age. At 24 wk of age, chicks were orally gavaged with 1 × 109 CFU Salmonella Enteritidis. At 8 d post-Salmonella challenge, birds supplemented with acidifier in the challenge group had decreased (P = 0.04) cecal S. Enteritidis percentage by 100% compared to the challenge group without acidifier. At 3 (P = 0.03), 8 (P < 0.01), and 17 (P < 0.01) d post-Salmonella challenge, acidifier supplementation increased cecal Bifidobacterium percentage by 98.2%, 99.7%, and 93.2% compared to the un-supplemented groups, respectively. At 24 d post-Salmonella challenge, acidifier supplementation had lower anti-Salmonella IgG titers in the vaccine + challenge group by 42.3% (0.33 OD value difference) compared to the vaccine + challenge group without acidifier supplementation (P < 0.05). The combined analysis of performance, immune response, and cecal microbiota indicates that acidifier supplementation can manipulate immune response and decrease Salmonella infection in laying hens.

BACKGROUND: Sub-Saharan African adolescents living with HIV face challenges to antiretroviral therapy (ART) adherence. Poor mental health drives non-adherence, but can be improved with cognitive behavioral therapy (CBT). CBT delivered by peers may strengthen effects while building capacity for sustainment in low-income countries. This case study retrospectively applied the Exploration Preparation Implementation Sustainment (EPIS) framework to characterize the execution of the Kigali Imbereheza Project (KIP), a 2-arm individually randomized group controlled trial of Trauma-Informed Adherence-Enhanced CBT (TI-CBTe) delivered by Rwandan youth leaders (YL) to adolescents living with HIV. METHODS: YL (n=14, 43% female, M=22.71 years-old) had confirmed HIV and self-reported ART adherence > 95%. Participants (n=356, 51% female, M=16.78 years-old) living with HIV were randomized to TI-CBTe or usual care. Two YL co-led TI-CBTe sessions over two months for a total of 12 hours, while other YL observed and rated fidelity. Participants reported on YL competence. Additional data evaluated feasibility, acceptability, uptake and fidelity. RESULTS: In the Exploration phase, focus groups, stakeholder meetings, and individual interviews revealed strong consensus for delivering TI-CBT to reduce adolescent depression and trauma and improve ART adherence. In the Preparation phase, curriculum revisions were made, YL were successfully trained, and a cascading supervision model was established. In the Implementation phase, YL delivered TI-CBTe with close monitoring and supervision. Findings revealed strong feasibility, acceptability, uptake and fidelity, increasing the likelihood of Sustainment. CONCLUSIONS: EPIS can guide implementation planning and delivery and evaluate implementation outcomes.

Repeated exposure to hurricanes and tropical storms likely impacts the mental and physical health of populations living along the U.S. Gulf Coast. In this study, the self-rated physical and mental health of residents in the U.S. Gulf Coast was estimated and factors associated with differences in self-rated health were identified. The 12-item Short Form Health Survey (SF-12) was administered online to a sample of 3030 residents of the U.S. Gulf Coast in December 2017. Responses were scored to calculate mental component summary scores and physical component summary scores. Multiple linear regression models were fitted to identify predictors of self-rated health among the residents. Residents of U.S. Gulf Coast States have poorer self-rated physical and mental health compared to the U.S. population. Women and respondents reporting higher perception of flood risk had worse self-rated mental health, while hurricane evacuees, adults of at least 25 years of age, those with self-reported hurricane damage, and respondents reporting higher perception of surge risk had worse self-rated physical health. Residents of U.S. Gulf Coast States have poorer self-rated health compared to national standards. These findings may have practical implications for hurricane-associated physical and mental health services planning and delivery.

Objective To evaluate the state of the science on uncertainty in high-risk pregnancy and identify factors that influence uncertainty in women diagnosed with a high-risk pregnancy. Data sources Primary research articles from CINAHL, Ovid, MEDLINE, Scopus, and PsycINFO written in English, without date restrictions. Study selection Nineteen articles were identified, including 14 qualitative studies and 5 quantitative studies. Data extraction This integrative review was guided by Whittemore and Knafl's methodology. Studies were graded on level and quality of evidence as per Dearholt, Dang, and Sigma Theta Tau International. Data synthesis Studies were synthesized by using constant comparative methods according to factors influencing, outcomes of, and management of uncertainty. Conclusion Uncertainty is a prominent theme in women experiencing a high-risk pregnancy. Uncertainty is influenced by various personal, pregnancy-related, demographic, and healthcare-related factors. Findings may offer insight and empathy for healthcare professionals. Nurses who understand significance of uncertainty in adjusting to two conflicting life events have the opportunity to help women in their understanding of a high-risk diagnosis during pregnancy through anticipatory guidance. Future research is needed to explore factors affecting uncertainty and to understand the experience of high-risk pregnancy to develop interventions aimed at mitigating uncertainty in high-risk pregnant women.

The expanding practice of multi-disciplinary care to address the complex nature of Autism Spectrum Disorder (ASD) suggests that there is a need for a means of coordinating care that transcends the disciplinary distinctions of relevant ASD treatment providers. As ASD services become more specialized, there is a growing need for effective care coordination with providers across the systems of care. Nursing professionals are ideally qualified to support families affected by ASD, as they provide a necessary holistic lens of health and wellbeing to obtain the appropriate treatments. Solution-focused brief therapy has been applied to a growing number of clinical settings, indicating solution-focused techniques are applicable to the various contexts associated with ASD treatments. We provide a case presentation to demonstrate a solution-focused approach to address ASD-related concerns within the family that are generalizable to coordination of care.

This literature review provides an overview of the research using magnetic resonance imaging (MRI) in pediatric migraine and compares findings with the adult migraine literature. A literature search using PubMed was conducted using all relevant sources up to February 2019. Using MRI methods to categorize and explain pediatric migraine in comparison with adult migraine is important, in order to recognize and appreciate the differences between the two entities, both clinically and physiologically. We aim to demonstrate the differences and similarities between pediatric and adult migraine using data from white matter and gray matter structural studies, cerebral perfusion, metabolites, and functional MRI (fMRI) studies, including task-based and resting-state blood oxygen level-dependent studies. By doing this we identify areas that need further research, as well as possible areas where intervention could alter outcomes.Utiliser des examens d’IRM dans le cas de jeunes patients souffrant de migraine. Cette revue de littérature entend fournir un survol des travaux de recherche explorant l’utilisation d’examens d’IRM dans le cas de jeunes patients souffrant de migraine. Elle vise aussi à comparer nos observations à celles que l’on trouve dans la littérature portant sur les cas de migraine chez les adultes. Au moyen de PubMed, nous avons effectué une recherche bibliographique pour ensuite utiliser toutes les références jugées pertinentes et publiées avant février 2019. Le fait d’utiliser des méthodes d’imagerie afin de catégoriser et d’expliquer les cas de migraine chez les enfants, et ce, en comparaison avec les cas de migraine chez l’adulte, est important afin de pouvoir reconnaître et d’identifier les différences tant sur le plan clinique que physiologique. Notre intention est ici de faire ressortir ces différences (mais aussi des similitudes) au moyen de données obtenues dans le cadre d’études structurales de la matière blanche et de la matière grise et d’études portant sur la perfusion cérébrale, les métabolites et les IRM fonctionnelles, ce qui inclut le signal BOLD (blood oxygen level dependent) à l’état de repos ou lors de l’exécution de tâches. En procédant à cette étude, nous voulons identifier les domaines qui devraient être explorés davantage de même que les domaines où des interventions pourraient modifier l’évolution de l’état de santé des patients.

Transcranial direct current stimulation (tDCS) has shown efficacy in augmenting the effects of language therapy in primary progressive aphasia (PPA). The mechanism of action of tDCS is not understood, but preliminary work in healthy adults suggests it modulates γ-aminobutyric acid (GABA) levels to create an environment optimal for learning. It is unknown if this proposed mechanism translates to aging or neurodegenerative conditions. This study tested the hypothesis that tDCS reduces GABA at the stimulated tissue in PPA. We applied GABA-edited magnetic resonance spectroscopy to quantify GABA levels before and after a sham-controlled tDCS intervention with language therapy in PPA. All participants showed improvements but those receiving active tDCS showed significantly greater language improvements compared to sham both immediately after the intervention and at 2-month follow-up. GABA levels in the targeted tissue decreased from baseline after the intervention and remained decreased 2 months after the intervention. This work supports the hypothesis that tDCS modulates GABAergic inhibition to augment learning and is clinically useful for PPA combined with language therapy.

Dual specificity phosphatase 6 (DUSP6) is a protein phosphatase that deactivates extracellular-signal-regulated kinase (ERK). Since the ovarian cancer biomarker human epididymis protein 4 (HE4) interacts with the ERK pathway, we sought to determine the relationship between DUSP6 and HE4 and elucidate DUSP6's role in epithelial ovarian cancer (EOC). Viability assays revealed a significant decrease in cell viability with pharmacological inhibition of DUSP6 using (E/Z)-BCI hydrochloride in ovarian cancer cells treated with carboplatin or paclitaxel, compared to treatment with either agent alone. Quantitative PCR was used to evaluate levels of ERK pathway response genes to BCI in combination with recombinant HE4 (rHE4), carboplatin, and paclitaxel. Expression of EGR1, a promoter of apoptosis, was higher in cells co-treated with BCI and paclitaxel or carboplatin than in cells treated with chemotherapeutic agents alone, while expression of the proto-oncogene c-JUN was decreased with co-treatment. The effect of BCI on the expression of these two genes opposed that of rHE4. Pathway focused quantitative PCR also revealed suppression of ERBB3 in cells co-treated with BCI plus carboplatin or paclitaxel. Finally, expression levels of DUSP6 in EOC tissue were evaluated by immunohistochemistry, revealing significantly increased levels of DUSP6 in serous EOC tissue compared to adjacent normal tissue. A positive correlation between HE4 and DUSP6 levels was determined by Spearman Rank correlation. In conclusion, DUSP6 inhibition sensitizes ovarian cancer cells to chemotherapeutic agents and alters gene expression of ERK response genes, suggesting that DUSP6 could plausibly function as a novel therapeutic target to reduce chemoresistance in EOC.

Purpose: The purpose of this study was to use a qualitative, community-based participatory action research method – Photovoice – to identify perceived facilitators and barriers to physical activity...

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels. ispartof: NEUROIMAGE vol:191 pages:537-548 ispartof: location:United States status: published

Low birth weight is associated with a greater prevalence of hypertension and an earlier age at menopause in women in later life. Yet, the association between birth weight and blood pressure (BP) in women as they age is not well defined. In a rodent model of low birth weight induced by placental insufficiency, intrauterine growth restriction programs a significant increase in BP by 12 months of age in female growth-restricted offspring that is associated with early reproductive senescence, increased testosterone, and a shift in the hormonal milieu. Thus, this study tested the hypothesis that increased BP in female growth-restricted offspring is abolished by chronic estradiol supplementation. Placebo or 17β-estradiol valerate mini pellets (1.5 mg for 60-day release) were administered at 12 months of age for 6 weeks. BP, measured in conscious catheterized rats, was significantly increased in placebo-treated growth-restricted relative to placebo-treated control. However, BP was not elevated in estradiol-treated growth-restricted relative to placebo-treated growth-restricted. Estradiol mediates its effects on BP via its receptors and the renin-angiotensin system. BP was decreased in growth-restricted offspring treated with a G-protein coupled receptor agonist, G1 (400 mg/kg for 2 weeks). Renal AT1aR (angiotensin type 1a receptor) and AT1bR (angiotensin type 1b receptor) and renal AR (androgen receptor) mRNA expression were elevated in vehicle-treated growth-restricted offspring, but not in G1-treated growth-restricted. Therefore, these data suggest that chronic estradiol supplementation prevents the increase in BP that develops in female growth-restricted offspring via actions that may involve its G-protein coupled receptor and the renin-angiotensin system.

The bilaterally symmetrical, feeding larval stage is an ancestral condition in echinoderms. However, many echinoderms have evolved abbreviated development and form a pentamerous juvenile without a feeding larva. Abbreviated development with a non-feeding vitellaria larva is found in five families of brittle stars, but very little is known about this type of development. In this study, the external anatomy, ciliary bands, neurons, and muscles were examined in the development of the brooded vitellaria larva of Ophioplocus esmarki. The external morphology throughout development shows typical vitellaria features, including morphogenetic movements to set up the vitellaria body plan, an anterior preoral lobe, a posterior lobe, transverse ciliary bands, and development of juvenile structures on the mid-ventral side. An early population of neurons forms at the base of the preoral lobe at the pre-vitellaria stage after the initial formation of the coelomic cavities. These early neurons may be homologous to the apical neurons that develop in echinoderms with feeding larval forms. Neurons form close to the ciliary bands, but the vitellaria larva lacks the tracts of neurons associated with the ciliary bands found in echinoderms with feeding larvae. Additional neurons form in association with the axial complex and persist into the juvenile stage. Juvenile nerves and muscles form with pentamerous symmetry in the late vitellaria stage in a manner similar to their development within the late ophiopluteus larva. Even though O. esmarki is a brooding brittle star, its developmental sequence retains the general vitellaria shape and structure; however, the vitellaria larvae are unable to swim in the water column.

BACKGROUND: In numerous case-control studies, essential tremor (ET) has been associated with cognitive impairment. ET is often familial. However, cognitive impairment has not been studied in family members of ET cases. Endophenotypes are measurable clinical characteristics that may be present in individuals with increased risk for disease; as such, they may be present before disease onset. We administered a global cognitive screen to first-degree relatives of ET cases (FD-ET) and age-matched controls (Co). METHODS: We administered the Montreal Cognitive Assessment (MoCA) to 156 FD-ET and 73 Co, none of whom were diagnosed with ET or reported tremor. MoCA

Mastocytosis is an accumulation of clonal mast cells within tissues, commonly caused by mutations in the KIT proto-oncogene. This report describes the management of a neonate with diffuse cutaneous mastocytosis (DCM) caused by a rare activating KIT mutation, specifically internal tandem duplication of the Ala502Tyr503 pair on exon 9, and reviews current data regarding work-up of DCM in pediatric patients.

There is little evidence for effectiveness of team-based learning (TBL) in specialties such as Surgery. We developed and instituted TBLs in surgery clerkship and compared National Board of Medical Examiners (NBME) Surgery Subject Exam scores before and after implementation. We also analyzed students' feedback for their perception of TBLs.The TBLs were transitioned into the curriculum during the 2013-2014 academic year. The "before" and "after" implementation periods were 2011-2013 and 2014-2016, respectively. NBME Surgery Subject Examination scores at our institution and nationally were compared using the independent samples t test. Satisfaction with the clerkship was assessed with Association of American Medical Colleges Graduate Questionnaire data. Student feedback regarding TBL was gathered at the end of each surgery rotation and were analyzed for themes, both positive and negative.Mean NBME score was higher at our institution than nationally, both before (77.10 ± 8.75 vs. 75.20 ± 8.95, p = 0.032) and after (74.65 ± 8.0 vs. 73.10 ± 8.55, p = 0.071) TBL implementation. The mean score decreased following TBL implementation at our medical school (77.10 ± 8.75 vs. 74.65 ± 8.00, p = 0.039), but it was also lower nationally (75.20 ± 8.95 vs. 73.10 ± 8.55, p0.001). Further, students were more likely to rate the surgery clerkship as "good and/or excellent" on the Association of American Medical Colleges Graduate Questionnaire after TBL implementation (84.6% vs. 73.7%). In qualitative assessment, learners stated that TBLs were informative, helpful in studying for the shelf exam, and viewed them as an opportunity for interactive learning, and thus requested more TBLs. Areas for improvement included reading materials, directions, and organization of sessions.Student perception of TBL into our surgery clerkship has been both positive and provided feedback for improvement. In addition, our medical school graduates have continued to assess their surgery experience as "good" or "excellent" by a large majority. Concurrently, our NBME scores remain above the national mean. We believe our medical students benefit from a well-organized TBL and its active approach to learning during the surgery clerkship with no loss of fundamental surgery knowledge.

Often referred to as miscarriage, Early Pregnancy Loss (EPL) is the spontaneous death of a fetus experienced within the first 20 weeks of gestation and is the most common complication in pregnancy. Symptoms of an impending EPL are routinely managed in the Emergency Department (ED). EPL can have a substantial impact on women, potentially leading to psychological and emotional health issues and risks to future pregnancies. Despite the high prevalence of EPL, many women suffer in silence due to the common societal belief that EPL are insignificant. Many women experience EPL as an ambiguous loss and are at risk for disenfranchised grief. Compassionate, patient-centred care has been identified by women as an essential and often missing aspect of ED care and can have a profound impact on the overall well-being of women after EPL. Social workers play a critical role in the ED given that they prioritize the psychosocial well-being of patients in a system that is structured to primarily address trauma care. In an effort to reduce the psychological impact and complicated grief reactions of women experiencing EPL, specific recommendations for social work intervention to address the individual needs of women experiencing EPL in the ED are presented. These include acknowledging the loss, providing psychoeducation, honouring the loss, assessing resources, referral and additional information, and building capacity in the ED.

Abiotic and biotic factors control ecosystem biodiversity, but their relative contributions remain unclear. The ultraoligotrophic ecosystem of the Antarctic Dry Valleys, a simple yet highly heterogeneous ecosystem, is a natural laboratory well-suited for resolving the abiotic and biotic controls of community structure. We undertook a multidisciplinary investigation to capture ecologically relevant biotic and abiotic attributes of more than 500 sites in the Dry Valleys, encompassing observed landscape heterogeneities across more than 200 km2. Using richness of autotrophic and heterotrophic taxa as a proxy for functional complexity, we linked measured variables in a parsimonious yet comprehensive structural equation model that explained significant variations in biological complexity and identified landscape-scale and fine-scale abiotic factors as the primary drivers of diversity. However, the inclusion of linkages among functional groups was essential for constructing the best-fitting model. Our findings support the notion that biotic interactions make crucial contributions even in an extremely simple ecosystem., Charles Lee, Daniel Laughlin et al. use structural equation modeling to analyze ecological data from more than 500 sites in the Antarctic Dry Valleys. They find that although abiotic factors are the primary drivers of biodiversity variation, biotic interactions are needed to explain the data fully and may play previously underestimated roles.

Purpose Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. Method A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). Results Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. Discussion This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.

International audience; Plants often associate with specialized decomposer communities that increase plant litter breakdown, a phenomenon that is known as the 'home-field advantage' (HFA). Although the concept of HFA has long considered only the role of the soil microbial community, explicit consideration of the role of the microbial community on the foliage before litter fall (i.e. the phyllosphere community) may help us to better understand HFA. We investigated the occurrence of HFA in the presence vs absence of phyllosphere communities and found that HFA effects were smaller when phyllosphere communities were removed. We propose that priority effects and interactions between phyllosphere and soil organisms can help explain the positive effects of the phyllosphere at home, and suggest a path forward for further investigation.

The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG) in Europe monitor efficacy of contraceptive products in participating institutions and use those results to inform contraceptive recommendations. This study used the joint RMC-RMG Contraception Database to analyze efficacy of deslorelin implants (Suprelorin®), a contraceptive used in a wide range of mammalian taxa. More recently its use has increased in birds and in some reptiles and fish. Deslorelin, a gonadotropin-releasing hormone (GnRH) agonist, stimulates the reproductive system before downregulating receptors on pituitary cells that produce hormones that stimulate gonadal steroids in both males (testosterone) and females (estradiol and progesterone), interrupting sperm production and ovulation, respectively. Nevertheless, it has been used mostly in females. Efficacy has been high in mammals, with failures resulting in offspring in only 1.3% of treated individuals and 0.5% of treatment bouts. The failure rate has been higher in birds, with 14.7% of individuals in 7.2% of bouts producing eggs, perhaps reflecting differences in avian GnRH molecules. Too few reptiles and fish have been treated for meaningful analysis. Although deslorelin appears very safe, a possible exception exists in carnivores, because the stimulatory phase can result in ovulation and subsequent sustained progesterone secretion that may cause endometrial pathology. However, the stimulatory phase can be prevented by treatment with megestrol acetate for 7 d before and 7 d after implant insertion. The two current formulations of Suprelorin are effective for minimums of 6 (4.7 mg) or 12 mo (9.4 mg). The data indicate that Suprelorin is an effective and safe contraceptive option for female mammals, although it may not be effective in males of some mammalian species. Further research is needed to ascertain its usefulness in nonmammalian taxa.

BACKGROUND The purpose of this study was to evaluate the association between pre-injury Katz Index of Independence in Activities of Daily Living (Katz ADL) functional status and discharge to a facility in non-neurologically injured older trauma patients. METHODS Data were obtained from 207 patients in the Trauma Medical Home study cohort. Multivariable logistic regression was performed to identify factors associated with non-home discharge. RESULTS Average patient age was 67.9 (SD 11.1). Patients were predominantly white (89.4%) and female (52.2%) with a median ISS of 11 (IQR 9-14). The most common mechanism of injury was fall (48.3%), followed by motor vehicle crash (41.1%). Nearly all patients (94.7%) reported independence in activities of daily living prior to hospitalization for injury. Discharge disposition varied, 51.7% of patients were discharged home, 37.7% to subacute rehabilitation, 10.1% to acute rehabilitation and 0.5% to long-term acute care. There was no relationship between pre-injury independence and likelihood of discharge home (P = 0.1331). Age (P < 0.0001), BMI (P = 0.0002), Charlson comorbidity score of 3 or greater (P = 0.0187), being single (P = 0.0077), ISS ≥ 16 (P = 0.0075) and being female with self-reported symptoms of anxiety and/or depression over the past two weeks (P = 0.0092) were associated with significantly greater odds of non-home discharge. CONCLUSIONS Pre-injury Katz ADL is not associated with discharge disposition, though other significantly associated factors were identified. It is imperative that discussions regarding discharge disposition are initiated early during acute hospitalization. Trauma programs could potentially benefit from implementing an inpatient intervention focused on building coping skills for older patients exhibiting symptoms of anxiety or depression.

Background: Existing literature identifies a general positive benefit to students' examination scores when students change their answer on examinations. Current shifts toward computerized examinations and in test anxiety warrant a literature update on test-taking behaviors. Purpose: This study assessed answer changing on multiple-choice examinations and investigated faculty recommendations related to answer changing. Method: This study used a mixed-methods design using retrospective student data from ExamSoft reports and faculty responses from a national survey of nurse educators. Results: Findings indicated 55% of students improved their examination score, with an average improvement of 3%, and 24% of students lowered their examination score. However, faculty continue to incorrectly recommend that students should not change answers on examinations. Conclusion: The results of this study support prior literature that answer changing benefits students. However, data are lacking on the characteristics of students who improve or lower their examination scores by changing answers. [ J Nurs Educ . 2021;60(6):324–328.] .

Brain-computer interface and neuromodulation strategies relying on penetrating non-organic electrodes/optrodes are limited by an inflammatory foreign body response that ultimately diminishes performance. A novel "biohybrid" strategy is advanced, whereby living neurons, biomaterials, and microelectrode/optical technology are used together to provide a biologically-based vehicle to probe and modulate nervous-system activity. Microtissue engineering techniques are employed to create axon-based "living electrodes", which are columnar microstructures comprised of neuronal population(s) projecting long axonal tracts within the lumen of a hydrogel designed to chaperone delivery into the brain. Upon microinjection, the axonal segment penetrates to prescribed depth for synaptic integration with local host neurons, with the perikaryal segment remaining externalized below conforming electrical-optical arrays. In this paradigm, only the biological component ultimately remains in the brain, potentially attenuating a chronic foreign-body response. Axon-based living electrodes are constructed using multiple neuronal subtypes, each with differential capacity to stimulate, inhibit, and/or modulate neural circuitry based on specificity uniquely afforded by synaptic integration, yet ultimately computer controlled by optical/electrical components on the brain surface. Current efforts are assessing the efficacy of this biohybrid interface for targeted, synaptic-based neuromodulation, and the specificity, spatial density and long-term fidelity versus conventional microelectronic or optical substrates alone.

Background: Magnetic resonance spectroscopy (MRS) has been used to identify gamma-aminobutyric acid (GABA) alterations in mood disorders, particularly in the medial prefrontal cortex (mPFC) where decreased concentrations have been associated with anhedonia. In major depressive disorder (MDD), prior work suggests that repetitive transcranial magnetic stimulation (rTMS) increases mPFC GABA concentrations proportional to antidepressant response. To our knowledge, this has not been examined in acute bipolar depression.Methods: As part of a multicentre 4-week randomized, double-blind, sham-controlled trial using intermittent theta-burst stimulation (iTBS) of the left dorsolateral prefrontal cortex (DLPFC) in individuals with acute bipolar depression, we quantified mPFC GABA and Glx (glutamate+glutamine) concentrations using a 3T MRS scan at baseline and after the intervention. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale-17 (HRDS-17), and anhedonia was measured using the Snaith-Hamilton Pleasure Scale (SHAPS).Results: The trial was terminated for futility and magnetic resonance spectroscopy data was acquired for 18 participants. At baseline, there were no associations between GABA or Glx concentrations and anhedonia, however GABA was negative correlated with depressive symptom severity on the HRDS-17. Compared to the sham-iTBS group, participants receiving active-iTBS had a significant increase in mPFC GABA concentrations. This was unrelated to antidepressant outcomes or improvements in anhedonia.Conclusion: Our data suggests that iTBS targeting the DLPFC is associated with physiological changes in the mPFC. In acute bipolar depression, our preliminary data suggests that mPFC GABA is dissociated from antidepressant iTBS treatment outcomes and anhedonia.

Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of osteoarthritis (OA) has been of interest due to the immunomodulatory properties of these cells. Interleukin (IL)-10, a potent immunomodulatory cytokine, has also been investigated as an OA therapeutic. Therefore, the objective of this study was to evaluate the combinatorial effects of BM-MSCs and IL-10 in OA using a gene therapy approach. We hypothesized that BM-MSCs overexpressing IL-10 would have superior immunomodulatory effects leading to increased suppression of T cell proliferation and decreased production of proinflammatory cytokines, providing protection of the extracellular matrix (ECM) in a stimulated, co-culture OA model. Treatment groups included the following: untransduced BM-MSC, adeno-associated virus (AAV)-IL10-transduced BM-MSC, and AAV-null transduced BM-MSC, which were unstimulated or stimulated with IL-1β/tumor necrosis factor-α (TNF-α). T cell proliferation was significantly decreased by the presence of BM-MSCs, especially when these BM-MSCs were AAV transduced. There was no significant difference in T cell suppression when cells were cultured with AAV-IL10-transduced or AAV-null transduced BM-MSCs. AAV transduction itself was associated with decreased synthesis of IL-1β, IL-6, and TNF-α. Expression of IL-1β and MMP13 was downregulated in AAV-transduced BM-MSCs and MMP13 expression was downregulated in cartilage explants co-cultured with AAV-transduced BM-MSCs. Despite mitigation of some proinflammatory cascades, rescue of ECM loss, as determined by glycosaminoglycan quantification and histological evaluation, did not occur in either AAV-IL10-transduced or AAV-null transduced co-cultures. Although IL-10 overexpression may enhance BM-MSC-mediated T cell suppression, we did not observe significant modulation of inflammation-driven cartilage degradation in cultures containing AAV-IL10-transduced BM-MSCs. AAV transduction itself does appear to affect paracrine signaling by BM-MSCs, which warrants further investigation.

Accurate reference genome sequences provide the foundation for modern molecular biology and genomics as the interpretation of sequence data to study evolution, gene expression and epigenetics depends heavily on the quality of the genome assembly used for its alignment. Correctly organising sequenced fragments such as contigs and scaffolds in relation to each other is a critical and often challenging step in the construction of robust genome references. We previously identified misoriented regions in the mouse and human reference assemblies using Strand-seq, a single cell sequencing technique that preserves DNA directionality1, 2. Here we demonstrate the ability of Strand-seq to build and correct full-length chromosomes, by identifying which scaffolds belong to the same chromosome and determining their correct order and orientation, without the need for overlapping sequences. We demonstrate that Strand-seq exquisitely maps assembly fragments into large related groups and chromosome-sized clusters without using new assembly data. Using template strand inheritance as a bi-allelic marker, we employ genetic mapping principles to cluster scaffolds that are derived from the same chromosome and order them within the chromosome based solely on directionality of DNA strand inheritance. We prove the utility of our approach by generating improved genome assemblies for several model organisms including the ferret, pig, Xenopus, zebrafish, Tasmanian devil and the Guinea pig.

Background Unusual behavioral reactions to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features ( Methods Here, we used electroencephalography (EEG) to investigate tactile cortical processing in young children aged 3–6 years with autism and in neurotypical (NT) children. Scalp EEG was recorded from 33 children with autism, including those with low cognitive and/or verbal abilities, and 45 age- and sex-matched NT children during passive tactile fingertip stimulation. We compared properties of early and later somatosensory-evoked potentials (SEPs) and their adaptation with repetitive stimulation between autistic and NT children and assessed whether these neural measures are linked to “real-world” parent-reported tactile reactivity. Results As expected, we found elevated tactile reactivity in children on the autism spectrum. Our findings indicated no differences in amplitude or latency of early and mid-latency somatosensory-evoked potentials (P50, N80, P100), nor adaptation between autistic and NT children. However, latency of later processing of tactile information (N140) was shorter in young children with autism compared to NT children, suggesting faster processing speed in young autistic children. Further, correlational analyses and exploratory analyses using tactile reactivity as a grouping variable found that enhanced early neural responses were associated with greater tactile reactivity in autism. Limitations The relatively small sample size and the inclusion of a broad range of autistic children (e.g., with low cognitive and/or verbal abilities) may have limited our power to detect subtle group differences and associations. Hence, replications are needed to verify these results. Conclusions Our findings suggest that electrophysiological somatosensory cortex processing measures may be indices of “real-world” tactile reactivity in early childhood autism. Together, these findings advance our understanding of the neurophysiological mechanisms underlying tactile reactivity in early childhood autism and, in the clinical context, may have therapeutic implications.

Proton ((1)H) magnetic resonance spectroscopy provides a non-invasive and quantitative measure of brain metabolites. Traumatic brain injury impacts cerebral metabolism and a number of research groups have successfully used this technique as a biomarker of injury and/or outcome in both pediatric and adult TBI populations. However, this technique is underutilized, with studies being performed primarily at centers with access to MR research support. In this paper we present a technical introduction to the acquisition and analysis of in vivo (1)H magnetic resonance spectroscopy and review (1)H magnetic resonance spectroscopy findings in different injury populations. In addition, we propose a basic (1)H magnetic resonance spectroscopy data acquisition scheme (Supplemental Information) that can be added to any imaging protocol, regardless of clinical magnetic resonance platform. We outline a number of considerations for study design as a way of encouraging the use of (1)H magnetic resonance spectroscopy in the study of traumatic brain injury, as well as recommendations to improve data harmonization across groups already using this technique.

OBJECTIVE: Clinical rotations during medical school are the time when most students select their specialty. Limited or lack of exposure could deter students from certain sub-specialties, and thus, insight into the selection process is essential. This study assesses the role of limited clinical rotations and perception of students on specialty selection. METHODS: All graduating medical students were surveyed at our US-based institution for 2 years. The survey included both open- and close-ended questions related to influence of clerkship experience and other factors on specialty choice and suggestions for improvement. The data were analyzed descriptively and thematically. RESULTS: Majority of students (87%) had minimal exposure to their chosen residency specialty prior to the third-year clerkships. Role of a clerkship experience in selecting a specialty was significant for 70% students, especially interaction with attendings (92%) and residents (86.3%). The most influential reasons for specialty choice to change were clerkship experience (41%) and mentors (21%). Approximately 34% students chose a specialty that was not a part of third-year core clerkships, and the most significant factors influencing their choice were shadowing experience (21%) and lifestyle (18%). Further, thematic analysis suggested that earlier and more clinical exposure to various specialties and formal mentoring could make specialty selection process easier. CONCLUSIONS: Along with specialty content, the relationship of learners and teachers in the clinical setting plays a significant role in selecting and/or rejecting certain specialty by medical students. The study provides broader baseline data for medical schools and educators in preparation of curriculum and future physician workforce composition.

Background Consumer devices with broad reach may be useful in screening for atrial fibrillation (AF) in appropriate populations. However, currently no consumer devices are capable of continuous monitoring for AF. Objective The purpose of this study was to estimate the sensitivity and specificity of a smartwatch algorithm for continuous detection of AF from sinus rhythm in a free-living setting. Methods We studied a commercially available smartwatch with photoplethysmography (W-PPG) and electrocardiogram (W-ECG) capabilities. We validated a novel W-PPG algorithm combined with a W-ECG algorithm in a free-living setting, and compared the results to those of a 28-day continuous ECG patch (P-ECG). Results A total of 204 participants completed the free-living study, recording 81,944 hours with both P-ECG and smartwatch measurements. We found sensitivity of 87.8% (95% confidence interval [CI] 83.6%–91.0%) and specificity of 97.4% (95% CI 97.1%–97.7%) for the W-PPG algorithm (every 5-minute classification); sensitivity of 98.9% (95% CI 98.1%–99.4%) and specificity of 99.3% (95% CI 99.1%–99.5%) for the W-ECG algorithm; and sensitivity of 96.9% (95% CI 93.7%–98.5%) and specificity of 99.3% (95% CI 98.4%–99.7%) for W-PPG triggered W-ECG with a single W-ECG required for confirmation of AF. We found a very strong correlation of W-PPG in quantifying AF burden compared to P-ECG (r = 0.98). Conclusion Our findings demonstrate that a novel algorithm using a commercially available smartwatch can continuously detect AF with excellent performance and that confirmation with W-ECG further enhances specificity. In addition, our W-PPG algorithm can estimate AF burden. Further research is needed to determine whether this algorithm is useful in screening for AF in select at-risk patients.

Human genomes are typically assembled as consensus sequences that lack information on parental haplotypes. Here we describe a reference-free workflow for diploid de novo genome assembly that combines the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing1,2 with continuous long-read or high-fidelity3 sequencing data. Employing this strategy, we produced a completely phased de novo genome assembly for each haplotype of an individual of Puerto Rican descent (HG00733) in the absence of parental data. The assemblies are accurate (quality value > 40) and highly contiguous (contig N50 > 23 Mbp) with low switch error rates (0.17%), providing fully phased single-nucleotide variants, indels and structural variants. A comparison of Oxford Nanopore Technologies and Pacific Biosciences phased assemblies identified 154 regions that are preferential sites of contig breaks, irrespective of sequencing technology or phasing algorithms., Assembly of haplotype-resolved human genomes is achieved by combining short and long reads.