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1. An Examination of the Costs of Texas Community Colleges. REL 2023-142. Appendixes

Author

Regional Educational Laboratory Southwest (ED/IES), National Center for Education Evaluation and Regional Assistance (NCEE) (ED/IES), American Institutes for Research (AIR), Levin, J., Baker, B., Lee, J., Atchison, D., and Kelchen, R.

Abstract

The "Examination of the Costs of Texas Community Colleges" study examined the funding levels necessary for community colleges to meet their promise of providing an affordable and accessible pathway to a postsecondary certificate or degree. The study involved three types of analyses: a needs analysis, an equity analysis, and a cost function analysis. The findings from this study can inform Texas policymakers' efforts to distribute funding for community colleges to support equitable opportunities for all students to succeed in college. This document presents the following three appendixes that accompany the study: (1) Texas' Student Success Points performance-based funding system; (2) Data and methods; and (3) Supporting analyses. [For the full report, see ED623284.]

Published
2022

3. UNIVERSAL POST-THAW VIABILITY TESTING OF ALLOGENEIC HEMATOPOIETIC STEM CELL (HPC) COLLECTIONS SHOWS INCREASED RISK OF NON-ENGRAFTMENT AND DELAYED PLATELET ENGRAFTMENT IN PRODUCTS WITH DECREASED POST-THAW VIABLE CD34 (vCD34) YIELD.

Author

Vozniuk, D., primary, Pattarkine, R.S., additional, Ntrivalas, E., additional, Secka, O., additional, Dontsova, M., additional, Vladimirov, A., additional, Feuer, E., additional, Yang, C., additional, Kehn, D., additional, Johnson, A., additional, Wafa, F., additional, Levin, J., additional, Zhu, J., additional, Veliaj, J., additional, Sa, B., additional, Thomsen, M., additional, Elterman, D., additional, Kolovrat, A., additional, Borge, P.D., additional, Roshal, M., additional, and Maryamchik, E., additional

Published
2024
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4. Validation of a German version of the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID‐G) in Down's syndrome.

Author

Nuebling, G., Wagemann, O., Deb, S., Wlasich, E., Loosli, S. V., Sandkühler, K., Stockbauer, A., Prix, C., and Levin, J.

Subjects
DIAGNOSIS of Down syndrome, DIAGNOSIS of dementia, RESEARCH funding, QUESTIONNAIRES, RESEARCH methodology evaluation, INTERVIEWING, RESEARCH evaluation, DESCRIPTIVE statistics, PSYCHOMETRICS, RESEARCH methodology, STATISTICAL reliability, NEUROPSYCHOLOGICAL tests, COGNITION disorders, MEDICAL screening, SENSITIVITY & specificity (Statistics), INTER-observer reliability
Abstract

Background: People with Down's syndrome (DS) are at high risk of developing Alzheimer dementia (DS‐AD) due to a triplication of the amyloid precursor protein gene. While several tools to diagnose and screen for DS‐AD, such as the dementia screening questionnaire for individuals with intellectual disabilities (DSQIID), are available in English, validated German versions of such instruments are scarce. Methods: A German version of the DSQIID questionnaire (DSQIID‐G) was completed by caregivers before attending our specialist outpatient department for DS‐AD. All participants were assessed blind to DSQIID‐G scoring using clinical and neuropsychological examinations, including the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX‐DS). ICD‐10 and amyloid/tau/neurodegeneration (A/T/N) criteria were applied to detect and categorise cognitive decline. Results: Of 86 participants, 43 (50%) showed evidence of cognitive decline. A definite diagnosis of DS‐AD was reached in 17 (19.8%) and mild cognitive impairment in seven (8.3%) participants. Secondary causes of cognitive decline were determined among 13 (15.1%) participants, and in six (7%) cases, the diagnosis remained unclassifiable due to co‐morbidities. Compared with cognitively stable individuals, participants with cognitive decline (n = 43) displayed higher DSQIID‐G total scores [median (range): 3 (0–21) vs. 19 (0–48), P < 0.001]. A total score of >7 provided a sensitivity of 0.94 against a specificity of 0.76, to discriminate DS‐AD and participants without cognitive decline according to ROC analysis. The convergent validity against the CAMDEX‐DS interview score was good (r = 0.74), and split‐half reliability (r = 0.96), internal consistency (Cronbach's α r = 0.96), test–retest reliability (r = 0.88) (n = 25) and interrater reliability (r = 0.81) (n = 31) were excellent. Conclusions: The DSQIID‐G showed excellent psychometric properties, including concurrent and internal validity and reliability. The cut‐off value for screening was lower than in the original English validation study. For a screening instrument like DSQIID‐G, a lower cut‐off is preferable to increase case detection. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Trucking Fleet Concept of Operations for Automated Driving System-equipped Commercial Motor Vehicles

Author

Krum, Andrew, Mabry, J. Erin, Hanowski, Richard J., Stojanovski, O., Manke, A., Adebisi, A., Hammond, R., Hickman, Jeffrey S., Miller, A., Camden, M., Potts, I., Harwood, D., Jin, X., Pugliese, B., Ridgeway, C., Werner, A., Walker, M., Kerns, L., Meissner, K., Parks, L., Argueta, O., Griffor, E., Sarkar, A., Stephens, M., Yang, G., Levin, J., Faulkner, D., Petersen, M., Golusky, M., Tidwell, S., Crowder, T., Bragg, H., Terranova, P., Thapa, S., Krum, Andrew, Mabry, J. Erin, Hanowski, Richard J., Stojanovski, O., Manke, A., Adebisi, A., Hammond, R., Hickman, Jeffrey S., Miller, A., Camden, M., Potts, I., Harwood, D., Jin, X., Pugliese, B., Ridgeway, C., Werner, A., Walker, M., Kerns, L., Meissner, K., Parks, L., Argueta, O., Griffor, E., Sarkar, A., Stephens, M., Yang, G., Levin, J., Faulkner, D., Petersen, M., Golusky, M., Tidwell, S., Crowder, T., Bragg, H., Terranova, P., and Thapa, S.

Abstract

The primary goals of the CONOPS project were to: i) collect information and practices on how to safely integrate ADS-equipped CMVs into the U.S. road transportation system; ii) provide the USDOT with data; iii) demonstrate how to integrate and deploy ADS-equipped trucks in a productive and cooperative way into the existing road freight ecosystem; and iv) collaborate with a broad and diverse group that includes government entities, university and research institutes, trucking associations, and private partners. This research found that the path forward to maintain public acceptance and achieve goals of ADS-equipped CMV operational cost-effectiveness, increased freight productivity, and reduction of crashes is through human operational assurance of vehicle, automation, freight, and public safety through specification, maintenance, inspections, monitoring, insurance, metrics, roadway assessment, and secure communications, as well as continuous lifecycle performance checks.

Published
2024

7. Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

Author

Pasternak, M., Mirza, S., Luciw, N., Mutsaerts, H., (0000-0002-3201-6002) Petr, J., Thomas, D., Cash, D., Bocchetta, M., Tartaglia, C., Mitchell, S., Black, S., Freedman, M., Tang-Wai, D., Rogaeva, E., Russell, L., Bouzigues, A., Swieten, J., Jiskoot, L., Seelaar, H., Laforce Jr., R., Tiraboschi, P., Borroni, B., Galimberti, D., Rowe, J., Graff, C., Finger, E., Sandro, S., Mendonça, A., Butler, C., Gerhard, A., Sánchez-Valle, R., Moreno, F., Synofzik, M., Vandenberghe, R., Ducharme, S., Levin, J., Otto, M., Santana, I., Strafella, A., Macintosh, B., Rohrer, J., Masellis, M., Pasternak, M., Mirza, S., Luciw, N., Mutsaerts, H., (0000-0002-3201-6002) Petr, J., Thomas, D., Cash, D., Bocchetta, M., Tartaglia, C., Mitchell, S., Black, S., Freedman, M., Tang-Wai, D., Rogaeva, E., Russell, L., Bouzigues, A., Swieten, J., Jiskoot, L., Seelaar, H., Laforce Jr., R., Tiraboschi, P., Borroni, B., Galimberti, D., Rowe, J., Graff, C., Finger, E., Sandro, S., Mendonça, A., Butler, C., Gerhard, A., Sánchez-Valle, R., Moreno, F., Synofzik, M., Vandenberghe, R., Ducharme, S., Levin, J., Otto, M., Santana, I., Strafella, A., Macintosh, B., Rohrer, J., and Masellis, M.

Abstract

Genetic frontotemporal dementia is most commonly attributable to mutations in the C9orf72, GRN, or MAPT genes. The disease has near-complete penetrance, making presymptomatic carriers an ideal population for ascertaining the earliest changes in disease progression and the identification of suitable biomarkers for designing therapeutic trials when minimal neuronal loss has occurred. Cerebral perfusion, as measured by arterial spin labelling (ASL) MRI, has shown promise in being one such biomarker. However, longitudinal profiles of change in perfusion over time in presymptomatic carriers across all three genetic subgroups are lacking. Using data from the multicenter GENetic Frontotemporal dementia Initiative, we investigated longitudinal profiles of cerebral perfusion using ASL-MRI in C9orf72 (n = 42), GRN (n = 70), and MAPT (n = 31) presymptomatic mutation carriers and non-carrier controls (n = 158). ASL and T1w scans were processed with the ExploreASL pipeline to produce partial volume corrected perfusion images, which were parcellated to extract mean perfusion values from whole brain grey matter and regions defined by the second version of the automated anatomical atlas (AAL2). Linear mixed effects models were used to assess longitudinal perfusion change. Mutation carrier groups and non-carriers were statistically indistinguishable by baseline demographic and clinical measures. Decline in whole brain grey matter perfusion over time was more pronounced in all three carrier subgroups relative to controls, with changes most pronounced in GRN, followed by C9orf72 and MAPT variants. Additionally, GRN and MAPT groups featured global grey matter hypoperfusion relative to non-carrier controls as early as one year after baseline measurement, with C9orf72 featuring significant hypoperfusion after two years. Region of interest analysis demonstrated that each genetic subgroup had its own regional profile in terms of longitudinal perfusion decline. Perfusion decline in C9orf72

Published
2024

8. Single-Case Designs Technical Documentation

Author

What Works Clearinghouse (ED), Kratochwill, T. R., Hitchcock, J., Horner, R. H., Levin, J. R., Odom, S. L., Rindskopf, D. M, and Shadish, W. R.

Abstract

In an effort to expand the pool of scientific evidence available for review, the What Works Clearinghouse (WWC) assembled a panel of national experts in single-case design (SCD) and analysis to draft SCD Standards. SCDs are adaptations of interrupted time-series designs and can provide a rigorous experimental evaluation of intervention effects. SCDs can provide a strong basis for establishing causal inference, and these designs are widely used in applied and clinical disciplines in psychology and education, such as school psychology and the field of special education. In this paper, the panel provides an overview of SCDs, specifies the types of questions that SCDs are designed to answer, and discusses the internal validity of SCDs. The panel then proposes SCD Standards to be implemented by the WWC. The Standards are bifurcated into Design and Evidence Standards. The Design Standards evaluate the internal validity of the design. Reviewers assign the categories of "Meets Standards," "Meets Standards with Reservations," and "Does not Meet Standards" to each study based on the Design Standards. Reviewers trained in visual analysis will then apply the Evidence Standards to studies that meet standards with or without reservations, resulting in the categorization of each outcome variable as demonstrating "Strong Evidence," "Moderate Evidence," or "No Evidence." Appended are: (1) Attrition Diagram; and (2) Visual Analysis. (Contains 1 table, 11 figures and 16 footnotes.)

Published
2010

10. The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models

Author

Ford, Deborah, Robins, James M, Petersen, Maya L, Gibb, Diana M, Gilks, Charles F, Mugyenyi, Peter, Grosskurth, Heiner, Hakim, James, Katabira, Elly, Babiker, Abdel G, Walker, A Sarah, Grosskurth, H, Munderi, P, Kabuye, G, Nsibambi, D, Kasirye, R, Zalwango, E, Nakazibwe, M, Kikaire, B, Nassuna, G, Massa, R, Fadhiru, K, Namyalo, M, Zalwango, A, Generous, L, Khauka, P, Rutikarayo, N, Nakahima, W, Mugisha, A, Todd, J, Levin, J, Muyingo, S, Ruberantwari, A, Kaleebu, P, Yirrell, D, Ndembi, N, Lyagoba, F, Hughes, P, Aber, M, Lara, A Medina, Foster, S, Amurwon, J, Wakholi, B Nyanzi, Mugyenyi, P, Kityo, C, Ssali, F, Tumukunde, D, Otim, T, Kabanda, J, Musana, H, Akao, J, Kyomugisha, H, Byamukama, A, Sabiiti, J, Komugyena, J, Wavamunno, P, Mukiibi, S, Drasiku, A, Byaruhanga, R, Labeja, O, Katundu, P, Tugume, S, Awio, P, Namazzi, A, Bakeinyaga, GT, Katabira, H, Abaine, D, Tukamushaba, J, Anywar, W, Ojiambo, W, Angweng, E, Murungi, S, Haguma, W, Atwiine, S, Kigozi, J, Latif, A, Hakim, J, Robertson, V, Reid, A, Chidziva, E, Bulaya-Tembo, R, Musoro, G, Taziwa, F, Chimbetete, C, Chakonza, L, Mawora, A, Muvirimi, C, Tinago, G, Svovanapasis, P, Simango, M, Chirema, O, Machingura, J, Mutsai, S, Phiri, M, Bafana, T, Chirara, M, Muchabaiwa, L, Muzambi, M, Katabira, E, and Ronald, A

Subjects
Clinical Research, Clinical Trials and Supportive Activities, HIV/AIDS, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Female, HIV Infections, Humans, Male, Models, Statistical, Uganda, Zimbabwe, Africa, antiretroviral therapy, drug switching, dynamic marginal structural models, HIV, monitoring, DART Trial Team, Mathematical Sciences, Medical and Health Sciences, Epidemiology
Abstract

In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003-2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm(3) or non-Candida World Health Organization stage 4 event (with CD4 count

Published
2015

11. 144P Discovery of CBO421: A first-in-class drug Fc-conjugate (DFC), targeting CD73 in cancer

Author

Döhrmann, S., primary, Levin, J., additional, Dedeic, N., additional, Almaguer, A., additional, Zuill, D., additional, Abelovski, E., additional, Fortier, J., additional, Zhao, Q., additional, Hernandez, M., additional, Amundson, K., additional, Moniz, M., additional, Chen, H., additional, Panickar, D., additional, Lam, T., additional, Brady, T., additional, Borchardt, A., additional, Cole, J.N., additional, and Tari, L.W., additional

Published
2023
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12. 153P Discovery of a novel, dual CD73 and PD-1 targeting multispecific drug Fc-conjugate (DFC) for the treatment of cancer

Author

Levin, J., primary, Döhrmann, S., additional, Dedeic, N., additional, Almaguer, A., additional, Zuill, D., additional, Abelovski, E., additional, Fortier, J., additional, Zhao, Q., additional, Hernandez, M., additional, Amundson, K., additional, Moniz, M., additional, Chen, H., additional, Panickar, D., additional, Lam, T., additional, Brady, T., additional, Borchardt, A., additional, Cole, J.N., additional, Hough, G., additional, Locke, J.B., additional, and Tari, L.W., additional

Published
2023
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14. New Window Resonances in the Potassium 3s Photoabsorption Spectrum

Author

Koide, M., Koike, F., Wehlitz, R., Huang, M. -T., Nagata, T., Levin, J. C., Fritzsche, S., DePaola, B. D., Ohtani, S., and Azuma, Y.

Subjects
Physics - Atomic Physics
Abstract

The photoion spectrum of atomic potassium was measured over the 3s -> np excitation region with the photoion time-of-flight method and monochromatized synchrotron radiation. An unusual spectrum with paired windows structure was found instead of a simple regular Rydberg series. Such subsidiary windows have not been observed in the 3s -> np resonances of Ar, which has a closed outer shell. Based on Dirac-Fock calculations, the dual window structure at 36.7 eV and at 37.4 eV was assigned to the 3s^{-1}3p^{6}4s4p resonance. The line shape can be fitted by Fano's formula and the Fano parameters were obtained., Comment: 7 pages, 1 figure

Published
2002
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15. Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia

Author

Bussy, A., Levy, J., Best, T., Patel, R., Cupo, L., Van Langenhove, T., Nielsen, J., Pijnenburg, Y., Waldö, M., Remes, A., Schroeter, M., Santana, I., Pasquier, F., Otto, M., Danek, A., Levin, J., Le Ber, I., Vandenberghe, R., Synofzik, M., Moreno, F., de Mendonça, A., Sanchez‐Valle, R., Laforce, R., Langheinrich, T., Gerhard, A., Graff, C., Butler, C., Sorbi, S., Jiskoot, L., Seelaar, H., van Swieten, J., Finger, E., Tartaglia, M., Masellis, M., Tiraboschi, P., Galimberti, D., Borroni, B., Rowe, J., Bocchetta, M., Rohrer, J., Devenyi, G., Chakravarty, M., Ducharme, S., Esteve, A., Nelson, A., Bouzigues, A., Heller, C., Greaves, C., Cash, D., Thomas, D., Todd, E., Benotmane, H., Zetterberg, H., Swift, I., Nicholas, J., Samra, K., Russell, L., Shafei, R., Convery, R., Timberlake, C., Cope, T., Rittman, T., Benussi, A., Premi, E., Gasparotti, R., Archetti, S., Gazzina, S., Cantoni, V., Arighi, A., Fenoglio, C., Scarpini, E., Fumagalli, G., Borracci, V., Rossi, G., Giaccone, G., Di Fede, G., Caroppo, P., Prioni, S., Redaelli, V., Tang‐Wai, D., Rogaeva, E., Castelo‐Branco, M., Freedman, M., Keren, R., Black, S., Mitchell, S., Shoesmith, C., Bartha, R., Rademakers, R., Poos, J., Papma, J., Giannini, L., van Minkelen, R., Nacmias, B., Ferrari, C., Polito, C., Lombardi, G., Bessi, V., Veldsman, M., Andersson, C., Thonberg, H., Öijerstedt, L., Jelic, V., Thompson, P., Lladó, A., Antonell, A., Olives, J., Balasa, M., Bargalló, N., Borrego‐Ecija, S., Verdelho, A., Maruta, C., Ferreira, C., Miltenberger, G., do Couto, F., Gabilondo, A., Gorostidi, A., Villanua, J., Cañada, M., Tainta, M., Zulaica, M., Barandiaran, M., Alves, P., Bender, B., Wilke, C., Graf, L., Vogels, A., Vandenbulcke, M., Van Damme, P., Bruffaerts, R., Poesen, K., Rosa‐Neto, P., Gauthier, S., Camuzat, A., Brice, A., Bertrand, A., Funkiewiez, A., Rinaldi, D., Saracino, D., Colliot, O., Sayah, S., Prix, C., Wlasich, E., Wagemann, O., Loosli, S., Schönecker, S., Hoegen, T., Lombardi, J., Anderl‐Straub, S., Rollin, A., Kuchcinski, G., Bertoux, M., Lebouvier, T., Deramecourt, V., Santiago, B., Duro, D., Leitão, M., Almeida, M., Tábuas‐Pereira, M., Afonso, S., Engel, A., Polyakova, M., Erasmus MC other, Neurology, Radiology & Nuclear Medicine, Clinical Genetics, GENetic Frontotemporal dementia Initiative (GENFI), Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Bussy, Aurélie [0000-0001-6695-9941], Nielsen, Jørgen E [0000-0003-0453-5582], Borroni, Barbara [0000-0001-9340-9814], Bocchetta, Martina [0000-0003-1814-5024], Devenyi, Gabriel A [0000-0002-7766-1187], Apollo - University of Cambridge Repository, and Amsterdam Neuroscience - Neurodegeneration

Subjects
C9orf72 Protein, Radiological and Ultrasound Technology, Medizin, frontotemporal dementia, Neurology, Frontotemporal Dementia, Cerebellum, Humans, magnetic resonance imaging, genetics, neuropsychiatry, Radiology, Nuclear Medicine and imaging, Human medicine, ddc:610, Neurology (clinical), Atrophy, Anatomy, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein]
Abstract

Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Fonds de Recherche du Québec ‐ Santé, Funder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024, Funder: NIHR Rare Diseases Translational Research Collaboration, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

Published
2023
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19. Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales

Author

Samra, K, MacDougall, AM, Peakman, G, Bouzigues, A, Bocchetta, M, Cash, DM, Greaves, CV, Convery, RS, van Swieten, JC, Jiskoot, L, Seelaar, H, Butler, CR, Fenoglio, C, Rohrer, JD, Gerhard, A, Ducharme, S, Le Ber, I, Tiraboschi, P, Santana, I, Pasquier, F, Levin, J, Shoesmith, C, Otto, M, Russell, LL, Nelson, A, Cash, D, Thomas, DL, Todd, E, Ferrari, C, Benotmane, H, Timberlake, C, Gabilondo, A, Cope, T, Rittman, T, Benussi, A, Premi, E, Gasparotti, R, Thompson, P, Archetti, S, Fumagalli, G, do Couto, FS, Borracci, V, Polito, C, Rossi, G, Giaccone, G, Di Fede, G, Caroppo, P, Ferreira, CB, Prioni, S, Langheinrich, T, Redaelli, V, Lladó, A, Bartha, R, Tang-Wai, D, Rogaeva, E, Castelo-Branco, M, Freedman, M, Keren, R, Black, S, Mitchell, S, Miltenberger, G, Rademakers, R, Poos, J, Papma, JM, Giannini, L, van Minkelen, R, Pijnenburg, Y, Gauthier, S, Nacmias, B, Lombardi, G, Bessi, V, Veldsman, M, Andersson, C, Thonberg, H, Öijerstedt, L, Prix, C, Jelic, V, Antonell, A, Graff, C, Olives, J, Balasa, M, Bargalló, N, Borrego-Ecija, S, Verdelho, A, Kuchcinski, G, Maruta, C, Gorostidi, A, Laforce, R, Villanua, J, Wlasich, E, Cañada, M, Tainta, M, Zulaica, M, Barandiaran, M, Moreno, F, Alves, P, Bender, B, Bertoux, M, Wilke, C, Lebouvier, T, Camuzat, A, Graf, L, Vogels, A, Vandenbulcke, M, Van Damme, P, Bruffaerts, R, Poesen, K, Rosa-Neto, P, Sanchez-Valle, R, Brice, A, Bertrand, A, Funkiewiez, A, Rinaldi, D, Saracino, D, Colliot, O, Sorbi, S, Sayah, S, Wagemann, O, Loosli, S, Schönecker, S, Hoegen, T, Lombardi, J, Anderl-Straub, S, Nicholas, J, Rollin, A, Deramecourt, V, Arighi, A, Santiago, B, Duro, D, Leitão, MJ, Almeida, MR, Tábuas-Pereira, M, Gazzina, S, Afonso, S, Masellis, M, Tartaglia, C, Shafei, R, Rowe, JB, Borroni, B, Finger, E, Synofzik, M, Galimberti, D, Vandenberghe, R, de Mendonça, A, Cantoni, V, Genetic FTD Initiative (GENFI), Samra, Kiran [0000-0002-3105-7099], Apollo - University of Cambridge Repository, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Nelson, Annabel, Bocchetta, Martina, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, and Verdelho, Ana

Subjects
Progranulin, Clinical Neurology, C9ORF72, tau Proteins, AMYOTROPHIC-LATERAL-SCLEROSIS, diagnosis [Frontotemporal Dementia], C9orf72, Tremor, Genetics, Humans, ddc:610, genetics [Frontotemporal Dementia], genetics [C9orf72 Protein], MUTATION, Science & Technology, C9orf72 Protein, HERITABILITY, Amyotrophic Lateral Sclerosis, PROGRESSIVE SUPRANUCLEAR PALSY, COGNITIVE IMPAIRMENT, REPEAT EXPANSION, genetics [tau Proteins], Motor, PATHOLOGICAL FEATURES, Neurology, FOS: Biological sciences, Frontotemporal Dementia, Mutation, Human medicine, Neurosciences & Neurology, Neurology (clinical), Tau, TAU, Life Sciences & Biomedicine, Frontotemporal dementia, PARKINSONISM
Abstract

Funder: CIBERNED, Funder: Canadian Institutes of Health Research; doi: http://dx.doi.org/10.13039/501100000024, Funder: Lemaire Family Foundation, Funder: Swedish Frontotemporal Dementia Initiative, Funder: Italian Ministry of Health, Funder: Weston Brain Institute; doi: http://dx.doi.org/10.13039/100012479, Funder: Mady Browaaeys Fund, Funder: Miriam Marks Brain Research UK, Funder: Bluefield Project, OBJECTIVE: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). METHODS: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands). Frequency and severity of each motor symptom was assessed, and a principal component analysis (PCA) was performed to identify how the different motor symptoms loaded together. Finally, addition of a motor component to the CDR® plus NACC FTLD was investigated (CDR® plus NACC FTLD-M). RESULTS: 24.3% of mutation carriers had motor symptoms (31.7% C9orf72, 18.8% GRN, 19.3% MAPT) compared to 6.8% of controls. Slowness and gait disorder were the commonest in all genetic groups while tremor and falls were the least frequent. Symptom severity scores were similar to equivalent physical motor examination scores. PCA revealed that all motor symptoms loaded together so a single additional motor component was added to the CDR® plus NACC FTLD to form the CDR® plus NACC FTLD-M. Individual global scores were more severe with the CDR® plus NACC FTLD-M, and no patients with a clinically diagnosed motor disorder (ALS/FTD-ALS or parkinsonism) were classified anymore as asymptomatic (unlike the CDR® plus NACC FTLD alone). CONCLUSIONS: Motor features are present in mutation carriers at all disease stages across all three genetic groups. Inclusion of motor symptoms in a rating scale that can be used in future clinical trials will not only ensure a more accurate severity measure is recorded but that a wider spectrum of FTD phenotypes can be included in the same trial.

Published
2022
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21. Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort

Author

Samra, K, MacDougall, AM, Bouzigues, A, Bocchetta, M, Cash, DM, Greaves, CV, Convery, RS, van Swieten, JC, Jiskoot, L, Seelaar, H, Moreno, F, Sanchez-Valle, R, Laforce, R, Graff, C, Masellis, M, Tartaglia, MC, Rowe, JB, Borroni, B, Finger, E, Synofzik, M, Galimberti, D, Vandenberghe, R, de Mendonça, A, Butler, CR, Gerhard, A, Ducharme, S, Le Ber, I, Tiraboschi, P, Santana, I, Pasquier, F, Levin, J, Otto, M, Sorbi, S, Rohrer, JD, Russell, LL, and Print-Electronic

Subjects
language, C9orf72, progranulin, MAPT, genetic, frontotemporal dementia
Abstract

Data availability: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S0022510X23001727?via%3Dihub#s0100 . Copyright © 2023 The Authors. Objective To identify whether language impairment exists presymptomatically in genetic frontotemporal dementia (FTD), and if so, the key differences between the main genetic mutation groups. Methods 682 participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 290 asymptomatic and 82 prodromal mutation carriers (with C9orf72, GRN, and MAPT mutations) as well as 310 mutation-negative controls. Language was assessed using items from the Progressive Aphasia Severity Scale, as well as the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency task. Participants also underwent a 3 T volumetric T1-weighted MRI from which regional brain volumes within the language network were derived and compared between the groups. Results 3% of asymptomatic (4% C9orf72, 4% GRN, 2% MAPT) and 48% of prodromal (46% C9orf72, 42% GRN, 64% MAPT) mutation carriers had impairment in at least one language symptom compared with 13% of controls. In prodromal mutation carriers significantly impaired word retrieval was seen in all three genetic groups whilst significantly impaired grammar/syntax and decreased fluency was seen only in C9orf72 and GRN mutation carriers, and impaired articulation only in the C9orf72 group. Prodromal MAPT mutation carriers had significant impairment on the category fluency task and the BNT whilst prodromal C9orf72 mutation carriers were impaired on the category fluency task only. Atrophy in the dominant perisylvian language regions differed between groups, with earlier, more widespread volume loss in C9orf72, and later focal atrophy in the temporal lobe in MAPT mutation carriers. Conclusions Language deficits exist in the prodromal but not asymptomatic stages of genetic FTD across all three genetic groups. Improved understanding of the language phenotype prior to phenoconversion to fully symptomatic FTD will help develop outcome measures for future presymptomatic trials. The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research Unit and the University College London Hospitals Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd., funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Italian Ministry of Health (CoEN015 and Ricerca Corrente), the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, a Canadian Institutes of Health Research operating grant, the Alzheimer's Society grant (AS-PG-16-007), the Bluefield Project and the JPND GENFI-PROX grant (2019–02248). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). JBR is funded by the Wellcome Trust (103838) and the National Institute for Health Research Cambridge Biomedical Research Centre. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). RV's work is supported by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie. Several authors of this publication (JCvS, MS, RSV, AD, MO, RV, JDR) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND) - Project ID No 739510.

Published
2023

23. Higher systolic blood pressure in early-mid adulthood is associated with poorer cognitive performance in those with a dominantly inherited Alzheimer's disease mutation but not in non-carriers. Results from the DIAN study

Author

Xu, Y ; https://orcid.org/0000-0002-3793-7716, Aung, HL ; https://orcid.org/0000-0002-8867-3220, Bateman, RJ, Brooks, WS ; https://orcid.org/0000-0001-8603-4233, Chhatwal, J, Day, GS, Fagan, AM, Farlow, MR, Gordon, B, Kehoe, PG, Levin, J, Mori, H, Morris, JC, Wharton, W, Humburg, P ; https://orcid.org/0000-0002-3331-6496, Schofield, PR, Peters, R ; https://orcid.org/0000-0003-0148-3617, Xu, Y ; https://orcid.org/0000-0002-3793-7716, Aung, HL ; https://orcid.org/0000-0002-8867-3220, Bateman, RJ, Brooks, WS ; https://orcid.org/0000-0001-8603-4233, Chhatwal, J, Day, GS, Fagan, AM, Farlow, MR, Gordon, B, Kehoe, PG, Levin, J, Mori, H, Morris, JC, Wharton, W, Humburg, P ; https://orcid.org/0000-0002-3331-6496, Schofield, PR, and Peters, R ; https://orcid.org/0000-0003-0148-3617

Published
2023

26. Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN).

Author

McKay, NS, Gordon, BA, Hornbeck, RC, Dincer, A, Flores, S, Keefe, SJ, Joseph-Mathurin, N, Jack, CR, Koeppe, R, Millar, PR, Ances, BM, Chen, CD, Daniels, A, Hobbs, DA, Jackson, K, Koudelis, D, Massoumzadeh, P, McCullough, A, Nickels, ML, Rahmani, F, Swisher, L, Wang, Q, Allegri, RF, Berman, SB, Brickman, AM, Brooks, WS, Cash, DM, Chhatwal, JP, Day, GS, Farlow, MR, la Fougère, C, Fox, NC, Fulham, M, Ghetti, B, Graff-Radford, N, Ikeuchi, T, Klunk, W, Lee, J-H, Levin, J, Martins, R, Masters, CL, McConathy, J, Mori, H, Noble, JM, Reischl, G, Rowe, C, Salloway, S, Sanchez-Valle, R, Schofield, PR, Shimada, H, Shoji, M, Su, Y, Suzuki, K, Vöglein, J, Yakushev, I, Cruchaga, C, Hassenstab, J, Karch, C, McDade, E, Perrin, RJ, Xiong, C, Morris, JC, Bateman, RJ, Benzinger, TLS, Dominantly Inherited Alzheimer Network, McKay, NS, Gordon, BA, Hornbeck, RC, Dincer, A, Flores, S, Keefe, SJ, Joseph-Mathurin, N, Jack, CR, Koeppe, R, Millar, PR, Ances, BM, Chen, CD, Daniels, A, Hobbs, DA, Jackson, K, Koudelis, D, Massoumzadeh, P, McCullough, A, Nickels, ML, Rahmani, F, Swisher, L, Wang, Q, Allegri, RF, Berman, SB, Brickman, AM, Brooks, WS, Cash, DM, Chhatwal, JP, Day, GS, Farlow, MR, la Fougère, C, Fox, NC, Fulham, M, Ghetti, B, Graff-Radford, N, Ikeuchi, T, Klunk, W, Lee, J-H, Levin, J, Martins, R, Masters, CL, McConathy, J, Mori, H, Noble, JM, Reischl, G, Rowe, C, Salloway, S, Sanchez-Valle, R, Schofield, PR, Shimada, H, Shoji, M, Su, Y, Suzuki, K, Vöglein, J, Yakushev, I, Cruchaga, C, Hassenstab, J, Karch, C, McDade, E, Perrin, RJ, Xiong, C, Morris, JC, Bateman, RJ, Benzinger, TLS, and Dominantly Inherited Alzheimer Network

Abstract

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of 'sporadic' AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers.

Published
2023

27. Patterns and implications of neurological examination findings in autosomal dominant Alzheimer disease

Author

Voeglein, J, Franzmeier, N, Morris, JC, Dieterich, M, McDade, E, Simons, M, Preische, O, Hofmann, A, Hassenstab, J, Benzinger, TL, Fagan, A, Noble, JM, Berman, SB, Graff-Radford, NR, Ghetti, B, Farlow, MR, Chhatwal, JP, Salloway, S, Xiong, C, Karch, CM, Cairns, N, Perrin, RJ, Day, G, Martins, R, Sanchez-Valle, R, Mori, H, Shimada, H, Ikeuchi, T, Suzuki, K, Schofield, PR, Masters, CL, Goate, A, Buckles, V, Fox, NC, Chrem, P, Allegri, R, Ringman, JM, Yakushev, I, Laske, C, Jucker, M, Hoglinger, G, Bateman, RJ, Danek, A, Levin, J, Voeglein, J, Franzmeier, N, Morris, JC, Dieterich, M, McDade, E, Simons, M, Preische, O, Hofmann, A, Hassenstab, J, Benzinger, TL, Fagan, A, Noble, JM, Berman, SB, Graff-Radford, NR, Ghetti, B, Farlow, MR, Chhatwal, JP, Salloway, S, Xiong, C, Karch, CM, Cairns, N, Perrin, RJ, Day, G, Martins, R, Sanchez-Valle, R, Mori, H, Shimada, H, Ikeuchi, T, Suzuki, K, Schofield, PR, Masters, CL, Goate, A, Buckles, V, Fox, NC, Chrem, P, Allegri, R, Ringman, JM, Yakushev, I, Laske, C, Jucker, M, Hoglinger, G, Bateman, RJ, Danek, A, and Levin, J

Abstract

INTRODUCTION: As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD. METHODS: Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers. RESULTS: AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, tremor, abnormal finger to nose and heel to shin testing, and compromised motor strength. The frequency of AD neurological examination findings was 65.1%. Cross-sectionally, mutation carriers with AD neurological examination findings showed a more than two-fold faster cognitive decline and had greater parieto-temporal atrophy, including hippocampal atrophy. Longitudinally, AD neurological examination findings predicted a significantly greater decline over time. DISCUSSION: ADAD features a distinct pattern of neurological examination findings that is useful to estimate prognosis and may inform clinical care and therapeutic trial designs.

Published
2023

28. Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome

Author

Katzdobler, S, Nitschmann, A, Barthel, H, Bischof, G, Beyer, L, Marek, K, Song, M, Wagemann, O, Palleis, C, Weidinger, E, Nack, A, Fietzek, U, Kurz, C, Haeckert, J, Stapf, T, Ferschmann, C, Scheifele, M, Eckenweber, F, Biechele, G, Franzmeier, N, Dewenter, A, Schoenecker, S, Saur, D, Schroeter, ML, Rumpf, J-J, Rullmann, M, Schildan, A, Patt, M, Stephens, AW, van Eimeren, T, Neumaier, B, Drzezga, A, Danek, A, Classen, J, Buerger, K, Janowitz, D, Rauchmann, B-S, Stoecklein, S, Perneczky, R, Schoeberl, F, Zwergal, A, Hoeglinger, GU, Bartenstein, P, Villemagne, V, Seibyl, J, Sabri, O, Levin, J, Brendel, M, Katzdobler, S, Nitschmann, A, Barthel, H, Bischof, G, Beyer, L, Marek, K, Song, M, Wagemann, O, Palleis, C, Weidinger, E, Nack, A, Fietzek, U, Kurz, C, Haeckert, J, Stapf, T, Ferschmann, C, Scheifele, M, Eckenweber, F, Biechele, G, Franzmeier, N, Dewenter, A, Schoenecker, S, Saur, D, Schroeter, ML, Rumpf, J-J, Rullmann, M, Schildan, A, Patt, M, Stephens, AW, van Eimeren, T, Neumaier, B, Drzezga, A, Danek, A, Classen, J, Buerger, K, Janowitz, D, Rauchmann, B-S, Stoecklein, S, Perneczky, R, Schoeberl, F, Zwergal, A, Hoeglinger, GU, Bartenstein, P, Villemagne, V, Seibyl, J, Sabri, O, Levin, J, and Brendel, M

Abstract

PURPOSE: Early after [18F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [18F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [18F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. METHODS: Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0-60 min) [18F]PI-2620 PET imaging. Regional perfusion (0.5-2.5 min p.i.) and tau load (20-40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value - 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). RESULTS: Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from

Published
2023

29. Biomarker clustering in autosomal dominant Alzheimer's disease

Author

Luckett, PH, Chen, C, Gordon, BA, Wisch, J, Berman, SB, Chhatwal, JP, Cruchaga, C, Fagan, AM, Farlow, MR, Fox, NC, Jucker, M, Levin, J, Masters, CL, Mori, H, Noble, JM, Salloway, S, Schofield, PR, Brickman, AM, Brooks, WS, Cash, DM, Fulham, MJ, Ghetti, B, Jack, CR, Voeglein, J, Klunk, WE, Koeppe, R, Su, Y, Weiner, M, Wang, Q, Marcus, D, Koudelis, D, Joseph-Mathurin, N, Cash, L, Hornbeck, R, Xiong, C, Perrin, RJ, Karch, CM, Hassenstab, J, McDade, E, Morris, JC, Benzinger, TLS, Bateman, RJ, Ances, BM, Luckett, PH, Chen, C, Gordon, BA, Wisch, J, Berman, SB, Chhatwal, JP, Cruchaga, C, Fagan, AM, Farlow, MR, Fox, NC, Jucker, M, Levin, J, Masters, CL, Mori, H, Noble, JM, Salloway, S, Schofield, PR, Brickman, AM, Brooks, WS, Cash, DM, Fulham, MJ, Ghetti, B, Jack, CR, Voeglein, J, Klunk, WE, Koeppe, R, Su, Y, Weiner, M, Wang, Q, Marcus, D, Koudelis, D, Joseph-Mathurin, N, Cash, L, Hornbeck, R, Xiong, C, Perrin, RJ, Karch, CM, Hassenstab, J, McDade, E, Morris, JC, Benzinger, TLS, Bateman, RJ, and Ances, BM

Abstract

INTRODUCTION: As the number of biomarkers used to study Alzheimer's disease (AD) continues to increase, it is important to understand the utility of any given biomarker, as well as what additional information a biomarker provides when compared to others. METHODS: We used hierarchical clustering to group 19 cross-sectional biomarkers in autosomal dominant AD. Feature selection identified biomarkers that were the strongest predictors of mutation status and estimated years from symptom onset (EYO). Biomarkers identified included clinical assessments, neuroimaging, cerebrospinal fluid amyloid, and tau, and emerging biomarkers of neuronal integrity and inflammation. RESULTS: Three primary clusters were identified: neurodegeneration, amyloid/tau, and emerging biomarkers. Feature selection identified amyloid and tau measures as the primary predictors of mutation status and EYO. Emerging biomarkers of neuronal integrity and inflammation were relatively weak predictors. DISCUSSION: These results provide novel insight into our understanding of the relationships among biomarkers and the staging of biomarkers based on disease progression.

Published
2023

31. Microglia drive TSPO PET signal increases in a tauopathy mouse model

Author

Englert, A. L., additional, Bartos, L. M., additional, Palleis, C., additional, Hummel, S., additional, Hörmann, L., additional, Schlaphoff, L., additional, Kunze, L. H., additional, Gnörich, J., additional, Wind-Mark, K., additional, Lindner, S., additional, Bartenstein, P., additional, Simons, M., additional, Ziegler, S., additional, Albert, N. L., additional, Levin, J., additional, and Brendel, M., additional

Published
2023
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32. 45P Discovery of CBO-212, a first-in-class drug Fc-conjugate (DFC), targeting CD73 in cancer

Author

Levin, J., primary, Döhrmann, S., additional, Dedeic, N., additional, Almaguer, A., additional, Zuill, D., additional, Abelovski, E., additional, Grewal, R., additional, Fortier, J., additional, Zhao, Q., additional, Hernandez, M., additional, Amundson, K., additional, Moniz, M., additional, Chen, H., additional, Panickar, D., additional, Lam, T., additional, Brady, T., additional, Borchardt, A., additional, Cole, J.N., additional, and Tari, L., additional

Published
2023
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35. Is perioperative COVID-19 really associated with worse surgical outcomes? A nationwide COVIDSurg propensity-matched analysis

Author

Argandykov, Dias, Dorken-Gallastegi, Ander, El Moheb, Mohamad, Gebran, Anthony, Proaño-Zamudio, Jefferson A, Bokenkamp, Mary, Renne, Angela M, Nepogodiev, Dmitri, Bhangu, Aneel, Kaafarani, Haytham M A, Kwabena, Siaw-Acheampong, Leah, Argus, Daoud, Chaudhry, Brett, E Dawson, James, C Glasbey, Rohan, R Gujjuri, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, James, M Keatley, Samuel, Lawday, Elizabeth, Li, Harvinder, Mann, Ella, J Marson, Kenneth, A Mclean, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana F, F Simoes, Isobel, M Trout, Mary, L Venn, Richard J, W Wilkin, Aneel, Bhangu, Dmitri, Nepogodiev, Irida, Dajti, Arben, Gjata, Luis, Boccalatte, Mariamarta, Modolo, Daniel, Cox, Peter, Pockney, Philip, Townend, Felix, Aigner, Irmgard, Kronberger, Kamral, Hossain, Gabrielle, Vanramshorst, Ismail, Lawani, Gustavo, Ataide, Glauco, Baiocchi, Igor, Buarque, Muhammad, Gohar, Mihail, Slavchev, Arnav, Agarwal, Amanpreet, Brar, Janet, Martin, Maria Marta Modolo, Maricarmen, Olivos, Jose, Calvache, Carlos Jose Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Jaroslav, Klat, René, Novysedlak, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango, Sameh, H Emile, Mengistu Gebreyohanes Mengesha, Samuel, Hailu, Hailu, Tamiru, Joonas, Kauppila, Johanna, Laukkarinen, Alexis, Arnaud, Markus, Albertsmeiers, Hans, Lederhuber, Markus, Loffler, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria Aguilera Lorena, Gustavo, Grecinos, Tamas, Mersich, Daniel, Wettstein, Dhruv, Ghosh, Gabriele, Kembuan, Peiman, Brouk, Mohammad, Khosravi, Masoud, Mozafari, Ahmed, Adil, Helen, M Mohan, Oded, Zmora, Marco, Fiore, Gallo, Gaetano, Francesco, Pata, Gianluca, Pellino, Sohei, Satoi, Faris, Ayasra, Mohammad, Chaar, Ildar, R Fakhradiyev, Mohammad, Jamal, Muhammed, Elhadi, Aiste, Gulla, April, Roslani, Laura, Martinez, Antonio Ramos De La Medina, Oumaima, Outani, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Willemijn van der Plas, Adesoji, Ademuyiwa, Babatunde, Osinaike, Justina, Seyi-Olajide, Emmanuel, Williams, Sofija, Pejkova, Knut Magne Augestad, Zainab Al Balushi, Ahmad, Qureshi, Raza, Sayyed, Mustafa Abu Mohsen Daraghmeh, Sadi, Abukhalaf, Moises, Cukier, Hugo, Gomez, Sebastian, Shu, Ximena, Vasquez, Marie Dione Parreno-Sacdalan, Piotr, Major, José, Azevedo, Miguel, Cunha, Irene, Santos, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Andrey, Litvin, Faustin, Ntirenganya, Ehab, Alameer, Dejan, Radenkovic, Frederick Koh Hong Xiang, Chew Min Hoe, James Ngu Chi Yong, Rachel, Moore, Ncamsile, Nhlabathi, Ruth Blanco Colino, Ana Minaya Bravo, Ana, Minaya-Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed, Elmujtaba, William, Jebril, Martin, Rutegård, Malin, Sund, Arda, Isik, Sezai, Leventoğlu, Tom E, F Abbott, Ruth, Benson, Caruna, Ed, Sohini, Chakrabortee, Andreas, Demetriades, Anant, Desai, Thomas, D Drake, John, G Edwards, Jonathan, P Evans, Samuel, Ford, Christina, Fotopoulou, Ewen, Griffiths, Peter, Hutchinson, Michael, D Jenkinson, Tabassum, Khan, Stephen, Knight, Angelos, Kolias, Elaine, Leung, Siobhan, Mckay, Lisa, Norman, Riinu, Ots, Vidya, Raghavan, Keith, Roberts, Andrew, Schache, Richard, Shaw, Katie, Shaw, Neil, Smart, Grant, Stewart, Sudha, Sundar, Dale, Vimalchandran, Naomi, Wright, Sattar, Alshryda, Osaid, Alser, Kerry, Breen, Ian, Ganly, Haytham, Kaafarani, Brittany, Kendall, Hassan, Mashbari, Hamza Al Naggar, Dennis, Mazingi, J J, Wong, Napolitano, L, Hemmila, M, Amin, D, Abramowicz, S, S M, Roser, K A, Olson, Riley, C, Heron, C, Cardenas, T, Leede, E, Thornhill, M, A B, Haynes, Mcelhinney, K, Roward, S, M D, Trust, C E, Hill, P G, Teixeira, Etchill, E, Stevens, K, M R, Ladd, Long, C, Rose, J, Kent, A, Yesantharao, P, Vervoort, D, Jenny, H, Gabre-Kidan, A, Margalit, A, Tsai, L, Malapati, H, Yesantharao, L, Abdou, H, Diaz, J, Richmond, M, Clark, J, O'Meara, L, Hanna, N, Ying, Y, Fleming, J, Ovaitt, A, Gigliotti, J, Fuson, A, Cooper, Z, Salim, A, A Hirji, S, Brown, A, Chung, C, Hansen, L, U Okafor, B, Roxo, V, P Raut, C, S Jolissaint, J, A Mahvi, D, Kaafarani, H, Breen, K, Bankhead-Kendall, B, Alser, O, Mashbari, H, Velmahos, G, L R, Maurer, El Moheb, M, Gaitanidis, A, Naar, L, M A, Christensen, Kapoen, C, Langeveld, K, El Hechi, M, Mokhtari, A, H Haqqani, M, T Drake, F, Goldenberg-Sandau, A, Galbreath, B, Reinke, C, Ross, S, Thompson, K, Manning, D, Perkins, R, Eriksson, E, Evans, H, Masrur, M, Giulianotti, P, Benedetti, E, Chang, G, Ourieff, J, Dehart, D, Dorafshar, A, Price, T, R Bhama, A, Torquati, A, Cherullo, E, Kennedy, R, Myers, J, Rubin, K, S Ban, V, G Aoun, S, H Batjer, H, Caruso, J, Carmichael, H, G Velopulos, C, L Wright, F, Urban, S, C McIntyre Jr, R, J Schroeppel, T, A Hennessy, E, Dunn, J, Zier, L, Burlew, C, Coleman, J, P Colling, K, Hall, B, E Rice, H, S Hwang, E, A Olson, S, Moris, D, Verma, R, Hassan, R, Volpe, A, Merola, S, A O'Banion, L, Lilienstein, J, Dirks, R, Marwan, H, Almasri, M, Kulkarni, G, Mehdi, M, Abouassi, A, Abdallah, M, M San Andrés, Eid, J, Aigbivbalu, E, Sundaresan, J, George, B, Ssentongo, A, Ssentongo, P, S Oh, J, Hazelton, J, Maines, J, Gusani, N, Garner, M, Horvath, S, Zheng, F, Ujiki, M, Kinnaman, G, Meagher, A, Sharma, I, Holler, E, Mckenzie, K, Chan, J, Fretwell, K, W Nugent 3rd, Khalil, A, Chen, D, Post, N, Rostkowski, T, Brahmbhatt, D, Huynh, K, L Hibbard, M, Schellenberg, M, Martin, Rcg, Bhutiani, N, Giorgakis, E, Laryea, J, Bhavaraju, A, Sexton, K, Roberts, M, Kost, M, Kimbrough, M, Burdine, L, Kalkwarf, K, Robertson, R, Gosain, A, Camp, L, Lewit, R, P Kronenfeld, J, Urrechaga, E, Goel, N, Rattan, R, Hart, V, Allen, M, Gilna, G, Cioci, A, Ruiz, G, Rakoczy, K, Pavlis, W, Saberi, R, Morris, R, S Karam, B, Brathwaite, Cem, Liu, H, Petrone, P, Hakmi, H, H Sohail, A, Baltazar, G, Heckburn, R, M Nygaard, R, T Colonna, E, W Endorf, F, J Hill, M, Maiga, A, Dennis, B, H Levin, J, Lallemand, M, Choron, R, Peck, G, Soliman, F, Rehman, S, Glass, N, Juthani, B, Deisher, D, M Ruzgar, N, J Ullrich, S, Sion, M, Paranjape, C, M El Moheb, R Kar, A, Gillezeau, C, Rapp, J, Taioli, E, A Miles, B, Alpert, N, Podolsky, D, L Coleman, N, P Callahan, M, Ganly, I, Brown, L, Monson, Jrt, Dehal, A, Abbas, A, Soliman, A, Kim, B, Jones, C, Dauer, E, Renza-Stingone, E, Hernandez, E, Gokcen, E, Kropf, E, Sufrin, H, Hirsch, H, Ross, H, Engel, J, Sewards, J, Poggio, J, Sanserino, K, Rae, L, Philp, M, Metro, M, Mcnelis, P, Petrov, R, Pazionis, T, Till, B, Lamm, R, J Rios-Diaz, A, Palazzo, F, Rosengart, M, Nicholson, K, M Carrick, M, Rodkey, K, Suri, A, Callcut, R, Nicholson, S, Talathoti, N, Klaristenfeld, D, Biffl, W, Marsh, C, Schaffer, K, E Berndtson, A, Averbach, S, Curry, T, Kwan-Feinberg, R, Consorti, E, Gonzalez, R, Grolman, R, Liu, T, Merzlikin, O, K Abel, M, Ozgediz, D, Boeck, M, Z Kornblith, L, Nunez-Garcia, B, Robinson, B, Park, P, F Utria, A, E Rice-Townsend, S, Javid, P, Hauptman, J, Kieran, K, Nehra, D, Walters, A, Cuschieri, J, H Davidson, G, Nunez, J, Cosker, R, Eckhouse, S, Choudhry, A, Marx, W, Jamil, T, Seegert, S, Al-Embideen, S, Quintana, M, Jackson, H, D Wexner, S, Kent, I, and N Martins, P

Subjects
COVID-19, COVIDSurg, mortality, postoperative complications, Surgery, Critical Care and Intensive Care Medicine
Published
2023

36. Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA

Author

Osaid, Alser, Ander Dorken Gallastegi, Anthony, Gebran, Kerry, Breen, Mohamad El Moheb, Apostolos, Gaitanidis, Leon, Naar, Brittany, Bankhead-Kendall, Hassan, Mashbari, Robert, D Sinyard, Lydia, R Maurer, Charu, Paranjape, George, C Velmahos, Dmitri, Nepogodiev, Aneel, Bhangu, Haytham M, A Kaafarani, Kwabena, Siaw-Acheampong, Leah, Argus, Daoud, Chaudhry, Brett, E Dawson, James, C Glasbey, Rohan, R Gujjuri, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, James, M Keatley, Samuel, Lawday, Elizabeth, Li, Harvinder, Mann, Ella, J Marson, Kenneth, A Mclean, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana F, F Simoes, Isobel, M Trout, Mary, L Venn, Richard J, W Wilkin, Irida, Dajti, Arben, Gjata, Oussama, Kacimi, Luis, Boccalatte, Maria Marta Modolo, Daniel, Cox, Peter, Pockney, Philip, Townend, Felix, Aigner, Irmgard, Kronberger, Ahmed, Elgun, Amer, Alderazi, Kamral, Hossain, Greg, Padmore, Gabrielle, Vanramshorst, Ismail, Lawani, Duane, Wedderburn, Sonam, Dargay, Israël, Feraudy, Cerovac, Anis, Samir, Delibegovic, Alemayehu Ginbo Bedada, Gustavo, Ataide, Glauco, Baiocchi, Igor, Buarque, Muhammad, Gohar, Mihail, Slavchev, Jean Marie Vianney Butoyi, Chukwuemeka, Nwegbu, Arnav, Agarwal, Amanpreet, Brar, Janet, Martin, Maricarmen, Olivos, Dong-Lin, Ren, Wenhui, Lou, Jose, Calvache, Carlos Jose Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Pablo, Avilés, Nikolaos, Gouvas, Jaroslav, Klat, René, Novysedlak, Nicolas, Amisi, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango, Sameh, H Emile, Danilo Alfonso Arévalo Sandoval, Mengistu Gebreyohanes Mengesha, Samuel, Hailu, Hailu, Tamiru, Joonas, Kauppila, Johanna, Laukkarinen, Alexis, Arnaud, Roumanatou Bankole Sapin, Kebba, Marenah, Zaza, Demetrashvili, Andreas, A Schnitzbauer, Magdalena, Gruendl, Markus, Albertsmeiers, Hans, Lederhuber, Markus, Loffler, Bernard Ofori Appiah, Daniel, Acquah, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria Aguilera Lorena, Gustavo, Grecinos, Tamas, Mersich, Daniel, Wettstein, Atul, Suroy, Dhruv, Ghosh, Pranay, Pawar, Gabriele, Kembuan, Peiman, Brouk, Mohammad, Khosravi, Masoud, Mozafari, Ahmed, Adil, Helen, M Mohan, Oded, Zmora, Marco, Fiore, Gallo, G, Pata, Francesco, Gianluca, Pellino, Naoto, Kuroda, Sohei, Satoi, Yuki, Fujimoto, Faris, Ayasra, Mohammad, Chaar, Ildar, R Fakhradiyev, Intisar, Hisham, Jin-Young, Jang, Enver, Fekaj, Mohammad, Jamal, Anvar, Beisembaev, Muhammed, Elhadi, Aiste, Gulla, Luc, Samison, Jupsi, Neny, Palesa, Chisala, April, Roslani, Iran Irani Duran Sanchez, Laura Martinez Perez Maldonado, Antonio Ramos De La Medina, Jade, Nunez, Oumaima, Outani, Abd'Rashid, Nashidengo, Ashish Lal Shrestha, Rakesh, Shah, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Willemijn van der Plas, Chris, Varghese, Deborah, Wright, Jorge, Neira, Adesoji, Ademuyiwa, Babatunde, Osinaike, Justina, Seyi-Olajide, Emmanuel, Williams, Sofija, Pejkova, Knut Magne Augestad, Kjetil, Soreide, Zainab Al Balushi, Ahmad, Qureshi, Raza, Sayyed, Mustafa Abu Mohsen Daraghmeh, Sadi, Abukhalaf, Moises, Cukier, Chris, Munguas, Hugo, Gomez, Sebastian, Shu, Ximena, Vasquez, Marie Dione Parreno-Sacdalan, Piotr, Major, José, Azevedo, Miguel, Cunha, Irene, Santos, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Andrey, Litvin, Faustin, Ntirenganya, Ehab, Alameer, Abdourahmane, Ndong, Dejan, Radenkovic, Ibrahim, Sesay, Frederick Koh Hong Xiang, Chew Min Hoe, James Ngu Chi Yong, Arpad, Panyko, Jurij, Kosir, Uros, Bele, Hassan, Ali, Rachel, Moore, Ncamsile, Nhlabathi, Ruth Blanco Colino, Ana Minaya Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed, Elmujtaba, William, Jebril, Martin, Rutegård, Malin, Sund, Eleftherios, Gialamas, Karoline, Horisberger, Michel, Adamina, Muhammad, Alshaar, Abel, Huang, Ben, Mbwele, Varut, Lohsiriwat, Shane, Charles, Haithem, Jlassi, Arda, Isik, Sezai, Leventoğlu, Lekuya, Herve, Lekuya, Monka, Herman, Lule, Tom E, F Abbott, Ruth, Benson, Caruna, Ed, Sohini, Chakrabortee, Andreas, Demetriades, Anant, Desai, Thomas, D Drake, John, G Edwards, Jonathan, P Evans, Samuel, Ford, Christina, Fotopoulou, Ewen, Griffiths, Peter, Hutchinson, Michael, D Jenkinson, Tabassum, Khan, Stephen, Knight, Angelos, Kolias, Elaine, Leung, Siobhan, Mckay, Lisa, Norman, Riinu, Ots, Vidya, Raghavan, Keith, Roberts, Andrew, Schache, Richard, Shaw, Katie, Shaw, Neil, Smart, Grant, Stewart, Sudha, Sundar, Dale, Vimalchandran, Naomi, Wright, Slava, Kopetskiy, Sattar, Alshryda, Ian, Ganly, Haytham, Kaafarani, Brittany, Kendall, Fernando, Bonilla, Hamza Al Naggar, Mayaba, Maimbo, Dennis, Mazingi, J Wong, J, Napolitano, L, Hemmila, M, Amin, D, Abramowicz, S, M Roser, S, A Olson, K, Riley, C, Heron, C, Cardenas, T, Leede, E, Thornhill, M, B Haynes, A, Mcelhinney, K, Roward, S, D Trust, M, E Hill, C, G Teixeira, P, Etchill, E, Stevens, K, R Ladd, M, Long, C, Rose, J, Kent, A, Yesantharao, P, Vervoort, D, Jenny, H, Gabre-Kidan, A, Margalit, A, Tsai, L, Malapati, H, Yesantharao, L, Abdou, H, Diaz, J, Richmond, M, Clark, J, O'Meara, L, Hanna, N, Ying, Y, Fleming, J, Ovaitt, A, Gigliotti, J, Fuson, A, Cooper, Z, Salim, A, A Hirji, S, Brown, A, Chung, C, Hansen, L, U Okafor, B, Roxo, V, P Raut, C, S Jolissaint, J, A Mahvi, D, Kaafarani, H, Breen, K, Bankhead-Kendall, B, Alser, O, Mashbari, H, Velmahos, G, R Maurer, L, M El Moheb, Gaitanidis, A, Naar, L, A Christensen, M, Kapoen, C, Langeveld, K, M El Hechi, Mokhtari, A, H Haqqani, M, T Drake, F, Goldenberg-Sandau, A, Galbreath, B, Reinke, C, Ross, S, Thompson, K, Manning, D, Perkins, R, Eriksson, E, Evans, H, Masrur, M, Giulianotti, P, Benedetti, E, Chang, G, Ourieff, J, Dehart, D, Dorafshar, A, Price, T, R Bhama, A, Torquati, A, Cherullo, E, Kennedy, R, Myers, J, Rubin, K, S Ban, V, G Aoun, S, H Batjer, H, Caruso, J, Carmichael, H, G Velopulos, C, L Wright, F, Urban, S, C McIntyre Jr, R, J Schroeppel, T, A Hennessy, E, Dunn, J, Zier, L, Burlew, C, Coleman, J, P Colling, K, Hall, B, E Rice, H, S Hwang, E, A Olson, S, Moris, D, Verma, R, Hassan, R, Volpe, A, Merola, S, A O'Banion, L, Lilienstein, J, Dirks, R, Marwan, H, Almasri, M, Kulkarni, G, Mehdi, M, Abouassi, A, Abdallah, M, M San Andrés, Eid, J, Aigbivbalu, E, Sundaresan, J, George, B, Ssentongo, A, Ssentongo, P, S Oh, J, Hazelton, J, Maines, J, Gusani, N, Garner, M, Horvath, S, Zheng, F, Ujiki, M, Kinnaman, G, Meagher, A, Sharma, I, Holler, E, Mckenzie, K, Chan, J, Fretwell, K, W Nugent 3rd, Khalil, A, Chen, D, Post, N, Rostkowski, T, Brahmbhatt, D, Huynh, K, L Hibbard, M, Schellenberg, M, R C, G Martin, Bhutiani, N, Giorgakis, E, Laryea, J, Bhavaraju, A, Sexton, K, Roberts, M, Kost, M, Kimbrough, M, Burdine, L, Kalkwarf, K, Robertson, R, Gosain, A, Camp, L, Lewit, R, P Kronenfeld, J, Urrechaga, E, Goel, N, Rattan, R, Hart, V, Allen, M, Gilna, G, Cioci, A, Ruiz, G, Rakoczy, K, Pavlis, W, Saberi, R, Morris, R, S Karam, B, C E, M Brathwaite, Liu, H, Petrone, P, Hakmi, H, H Sohail, A, Baltazar, G, Heckburn, R, M Nygaard, R, T Colonna, E, W Endorf, F, J Hill, M, Maiga, A, Dennis, B, H Levin, J, Lallemand, M, Choron, R, Peck, G, Soliman, F, Rehman, S, Glass, N, Juthani, B, Deisher, D, M Ruzgar, N, J Ullrich, S, Sion, M, Paranjape, C, R Kar, A, Gillezeau, C, Rapp, J, Taioli, E, A Miles, B, Alpert, N, Podolsky, D, L Coleman, N, P Callahan, M, Ganly, I, Brown, L, J R, T Monson, Dehal, A, Abbas, A, Soliman, A, Kim, B, Jones, C, D Dauer, M, Renza-Stingone, E, Hernandez, E, Gokcen, E, Kropf, E, Sufrin, H, Hirsch, H, Ross, H, Engel, J, Sewards, J, Poggio, J, Sanserino, K, Rae, L, Philp, M, Metro, M, Mcnelis, P, Petrov, R, Pazionis, T, Till, B, Lamm, R, J Rios-Diaz, A, Palazzo, F, Rosengart, M, Nicholson, K, M Carrick, M, Rodkey, K, Suri, A, Callcut, R, Nicholson, S, Talathoti, N, Klaristenfeld, D, Biffl, W, Marsh, C, Schaffer, K, E Berndtson, A, Averbach, S, Curry, T, Kwan-Feinberg, R, Consorti, E, Gonzalez, R, Grolman, R, Liu, T, Merzlikin, O, K Abel, M, Ozgediz, D, Boeck, M, Z Kornblith, L, Nunez-Garcia, B, Robinson, B, Park, P, F Utria, A, E Rice-Townsend, S, Javid, P, Hauptman, J, Kieran, K, Nehra, D, Walters, A, Cuschieri, J, H Davidson, G, Nunez, J, Cosker, R, Eckhouse, S, Choudhry, A, Marx, W, Jamil, T, Seegert, S, Al-Embideen, S, Quintana, M, Jackson, H, D Wexner, S, Kent, I, N Martins, P, Xiao, Liu, and Alistair, Denniston

Subjects
Male, medicine.medical_specialty, Revised Cardiac Risk Index, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pulmonary complications, Malignancy, Time-to-Treatment, Postoperative Complications, Sex Factors, Risk Factors, medicine, COVID-19, COVIDSurg, elective surgery, emergency surgery, mortality, pulmonary complications, Humans, In patient, Prospective Studies, emergency surgery, Elective surgery, Aged, Respiratory Distress Syndrome, SARS-CoV-2, business.industry, Pulmonary Complication, Age Factors, COVID-19, Pneumonia, Perioperative, Middle Aged, COVIDSurg, elective surgery, mortality, medicine.disease, United States, Surgery, Multicenter study, Elective Surgical Procedures, Female, business
Abstract

Objective To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Summary background data Uncertainty regarding the postoperative risks of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Methods As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results A total of 1,581 patients were included; more than half of them were males (n= 822, 52.0%) and older than 50 years (n=835, 52.8%). Most procedures (n=1,261, 79.8%) were emergent, and laparotomies (n= 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (OR 2.46, 95% CI [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.

Published
2021
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39. (Zugang zur) Diagnostik und Therapie demenzieller Erkrankungen bei Menschen mit einem Down-Syndrom (DS-Demenz)

Author

Walendzik, A, Wasem, J, Wagemann, O, Levin, J, Schall, A, Tesky, VA, Pantel, J, and Hüer, T

Subjects
ddc: 610, Medicine and health, Wirtschaftswissenschaften
Abstract

Hintergrund und Stand (inter)nationaler Forschung: Menschen mit einem Down-Syndrom haben ein deutlich erhöhtes Risiko, eine Demenz zu entwickeln. Dieses erhöhte Krankheitsrisiko trifft auf Herausforderungen in der Diagnostik und Therapie der Demenz in dieser Patientengruppe, die sich unterschiedlich [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Published
2022
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46. 20071. LA ASIMETRÍA CEREBRAL EN LA DEMENCIA FRONTOTEMPORAL POR MUTACIÓN EN GRN DISTINGUE ENTRE DOS SÍNDROMES Y PERMITE LA PREDICCIÓN DEL INICIO DE LA ENFERMEDAD

Author

Borrego Écija, S., Juncà Parella, J., Vandebergh, M., Pérez Millán, A., Balasa, M., Lladó, A., Bouzigues, A., Rusell, L., Foster, P., Ferry Bolder, E., van Swieten, J., Jiskoot, L., Seelaar, H., Laforce, R., Graff, C., Galimberti, D., Vandenberghe, R., de Mendonça, A., Tiraboschi, P., Santana, I., Gerhard, A., Levin, J., Sorbi, S., Otto, M., Pasquier, F., Ducharme, S., Butler, C., Le Ber, I., Finger, E., Tartaglia, M., Masellis, M., Rowe, J., Synofzik, M., Moreno, F., Borroni, B., Rademakers, R., Rohrer, J., and Sánchez del Valle, R.

Published
2024
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49. Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

Author

Panman, J. L., Venkatraghavan, V., Van Der Ende, E. L., Steketee, R. M. E., Jiskoot, L. C., Poos, J. M., Dopper, E. G. P., Meeter, L. H. H., Kaat, L. D., Rombouts, S. A. R. B., Vernooij, M. W., Kievit, A. J. A., Premi, E., Cosseddu, M., Bonomi, E., Olives, J., Rohrer, J. D., Sanchez-Valle, R., Borroni, B., Bron, E. E., Van Swieten, J. C., Papma, J. M., Klein, S., Afonso, S., Almeida, M. R., Anderl-Straub, S., Andersson, C., Antonell, A., Archetti, S., Arighi, A., Balasa, M., Barandiaran, M., Bargallo, N., Bartha, R., Bender, B., Black, S., Butler, C., Bocchetta, M., Borrego-Ecija, S., Bras, J., Bruffaerts, R., Caroppo, P., Cash, D., Castelo-Branco, M., Convery, R., Cope, T., Danek, A., De Arriba, M., De Mendonca, A., Di Fede, G., Diaz, Z., Ducharme, S., Duro, D., Fenoglio, C., Ferreira, C. B., Finger, E., Flanagan, T., Fox, N., Freedman, M., Fumagalli, G., Gabilondo, A., Galimberti, D., Gasparotti, R., Gauthier, S., Gazzina, S., Gerhard, A., Giaccone, G., Gorostidi, A., Graff, C., Greaves, C., Guerreiro, R., Heller, C., Hoegen, T., Indakoetxea, B., Jelic, V., Karnath, H. -O., Keren, R., Laforce, R., Leitao, M. J., Levin, J., Llado, A., Loosli, S., Maruta, C., Masellis, M., Mead, S., Miltenberger, G., Van Minkelenm Sara Mitchell, R., Moore, K., Moreno, F., Nicholas, J., Oijerstedt, L., Otto, M., Ourselin, S., Padovani, A., Peakman, G., Pijnenburg, Y., Polito, C., Prioni, S., Prix, C., Rademakers, R., Redaelli, V., Rittman, T., Rogaeva, E., Rosa-Neto, P., Rossi, G., Rosser, M., Rowe, J., Santana, I., Santiago, B., Scarpini, E., Schonecker, S., Shafei, E. S. R., Shoesmith, C., Synofzik, M., Tabuas-Pereira, M., Tagliavini, F., Tartaglia, C., Tainta, M., Taipa, R., Tang-Wai, D., Thomas, D. L., Thonberg, H., Timberlake, C., Tiraboschi, P., Todd, E., Vandamme, P., Vandenberghe, R., Vandenbulcke, M., Veldsman, M., Verdelho, A., Villanua, J., Warren, J., Wilkeione, C., Elisabeth, W., Henrik, W., Zulaica, Z. M., Neurology, Physics and medical technology, Radiology & Nuclear Medicine, Clinical Genetics, and Medical Research Council

Subjects
Male, Oncology, Disease, Neuropsychological Tests, GENFI consortium investigators, Primary progressive aphasia, Cognition, Progranulins, 0302 clinical medicine, Neurofilament Proteins, BEHAVIORAL VARIANT, HETEROGENEITY, Gray Matter, 11 Medical and Health Sciences, Language, Psychiatry, 0303 health sciences, Brain, Middle Aged, Magnetic Resonance Imaging, White Matter, 17 Psychology and Cognitive Sciences, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Phenotype, medicine.anatomical_structure, Frontotemporal Dementia, Disease Progression, Biomarker (medicine), Female, Life Sciences & Biomedicine, Frontotemporal dementia, medicine.medical_specialty, Clinical Neurology, EVENT-BASED MODEL, Grey matter, Lateralization of brain function, White matter, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, NEUROFILAMENT LIGHT-CHAIN, medicine, Humans, LOBAR DEGENERATION, PROGRANULIN, Aged, 030304 developmental biology, Science & Technology, Neurology & Neurosurgery, business.industry, DISEASE PROGRESSION, medicine.disease, Mutation, WHITE-MATTER INTEGRITY, Surgery, Neurosciences & Neurology, Neurology (clinical), business, GENFI, Biomarkers, 030217 neurology & neurosurgery, Progressive disease
Abstract

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.

Published
2021
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