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Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells

APOPTOSIS 2017年第5期22卷 730-740页

作者： Djiadeu, Pascal Kotra, Lakshmi P. Sweezey, Neil Palaniyar, Nades Hosp Sick Children Program Physiol & Expt Med Peter Gilgan Ctr Res & Learning Lung Innate Immun Res Lab 686 Bay St Toronto ON M5G 0A4 Canada Univ Toronto Leslie Dan Fac Pharm Dept Pharmaceut Sci Toronto ON M5S 3M2 Canada Univ Hlth Network Toronto Gen Res Inst Ctr Mol Design & Preformulat 101 Coll St Toronto ON M5G 1L7 Canada Univ Toronto Dept Lab Med Toronto ON M5G 1X8 Canada Univ Toronto Dept Pathobiol Toronto ON M5G 1X8 Canada Univ Toronto Fac Med Inst Med Sci Toronto ON M5G 1X8 Canada Hosp Sick Children Peter Gilgan Ctr Res & Learning Innate Immun Res Lab 686 Bay St Toronto ON M5G 0A4 Canada

Only a few extracellular soluble proteins are known to modulate apoptosis. We considered that surfactant-associated protein D (SP-D), an innate immune collectin present on many mucosal surfaces, could regulate apoptosis. Although SP-D is known to be important for immune cell homeostasis, whether SP-D affects apoptosis is unknown. In this study we aimed to determine the effects of SP-D on Jurkat T cells and human T cells dying by apoptosis. Here we show that SP-D binds to Jurkat T cells and delays the progression of Fas (CD95)-Fas ligand and TRAIL-TRAIL receptor induced, but not TNF-TNF receptor-mediated apoptosis. SP-D exerts its effects by reducing the activation of initiator caspase-8 and executioner caspase-3. SP-D also delays the surface exposure of phosphatidylserine. The effect of SP-D was ablated by the presence of caspase-8 inhibitor, but not by intrinsic pathway inhibitors. The binding ability of SP-D to dying cells decreases during the early stages of apoptosis, suggesting the release of apoptotic cell surface targets during apoptosis. SP-D also delays FasL-induced death of primary human T cells. SP-D delaying the progression of the extrinsic pathway of apoptosis could have important implications in regulating immune cell homeostasis at mucosal surfaces.

关键词： Surfactant protein D Collectins Mucosal surface Fas:Fas Ligand Extrinsic pathway of apoptosis

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Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021

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LANCET INFECTIOUS DISEASES 2024年第9期24卷 974-1002页

作者： Bender, Rose Grace Sirota, Sarah Brooke Swetschinski, Lucien R. Dominguez, Regina-Mae Villanueva Novotney, Amanda Wool, Eve E. Ikuta, Kevin S. Vongpradith, Avina Rogowski, Emma Lynn Best Doxey, Matthew Troeger, Christopher E. Albertson, Samuel B. Ma, Jianing He, Jiawei Maass, Kelsey Lynn Simoes, Eric A. F. Abdoun, Meriem Aziz, Jeza Muhamad Abdul Abdulah, Deldar Morad Abu Rumeileh, Samir Abualruz, Hasan Aburuz, Salahdein Adepoju, Abiola Victor Adha, Rishan Adikusuma, Wirawan Adra, Saryia Afraz, Ali Aghamiri, Shahin Agodi, Antonella Ahmadzade, Amir Mahmoud Ahmed, Haroon Ahmed, Ayman Akinosoglou, Karolina AL-Ahdal, Tareq Mohammed Ali Al-amer, Rasmieh Mustafa Albashtawy, Mohammed AlBataineh, Mohammad T. Alemi, Hediyeh Al-Gheethi, Adel Ali Saeed Ali, Abid Ali, Syed Shujait Shujait Alqahtani, Jaber S. AlQudah, Mohammad Al-Tawfiq, Jaffar A. Al-Worafi, Yaser Mohammed Alzoubi, Karem H. Amani, Reza Amegbor, Prince M. Ameyaw, Edward Kwabena Amuasi, John H. Anil, Abhishek Anyanwu, Philip Emeka Arafat, Mosab Areda, Damelash Arefnezhad, Reza Atalell, Kendalem Asmare Ayele, Firayad Azzam, Ahmed Y. Babamohamadi, Hassan Babin, Francois-Xavier Bahurupi, Yogesh Baker, Stephen Banik, Biswajit Barchitta, Martina Barqawi, Hiba Jawdat Basharat, Zarrin Baskaran, Pritish Batra, Kavita Batra, Ravi Bayileyegn, Nebiyou Simegnew Beloukas, Apostolos Berkley, James A. Beyene, Kebede A. Bhargava, Ashish Bhattacharjee, Priyadarshini Bielicki, Julia A. Bilalaga, Mariah Malak Bitra, Veera R. Brown, Colin Stewart Burkart, Katrin Bustanji, Yasser Carr, Sinclair Chahine, Yaacoub Chattu, Vijay Kumar Chichagi, Fatemeh Chopra, Hitesh Chukwu, Isaac Sunday Chung, Eunice Dadana, Sriharsha Dai, Xiaochen Dandona, Lalit Dandona, Rakhi Darban, Isaac Dash, Nihar Ranjan Dashti, Mohsen Dashtkoohi, Mohadese Dekker, Denise Myriam Delgado-Enciso, Ivan Devanbu, Vinoth Gnana Chellaiyan Dhama, Kuldeep Diao, Nancy Thao Huynh Phuong Do Dokova, Klara Georgieva Dolecek, Christiane Dziedzic, Arkadiusz Marian Eckmanns, Tim Ed-Dra, Abdelaziz Efendi, Ferry Eftekharimehrabad, A Univ Washington Inst Hlth Metr & Evaluat Seattle WA 98195 USA Univ Washington Sch Med Dept Hlth Metr Sci Seattle WA 98195 USA Univ Washington Dept Internal Med Seattle WA 98195 USA Univ Washington Dept Cardiol Seattle WA 98195 USA Univ Washington Dept Biostat Seattle WA 98195 USA Univ Washington Dept Global Hlth Seattle WA 98195 USA Univ Washington Dept Pharm Seattle WA 98195 USA Univ Washington Dept Appl Math Seattle WA 98195 USA Yale Univ Sch Med New Haven CT USA Yale Univ Dept Dermatol New Haven CT 06520 USA Vet Affairs Greater Los Angeles Div Infect Dis Los Angeles CA USA Emory Univ Sch Med Atlanta GA USA Seattle Indian Hlth Board Urban Indian Hlth Inst Seattle WA USA Ohio State Univ Ctr Biostat Columbus OH 43210 USA Univ Colorado Ctr Global Hlth Denver CO 80202 USA Univ Setif Algeria Dept Med Setif Algeria Univ Human Dev Dept Med Lab Sci Sulaymaniyah Iraq Baxshin Hosp Baxshin Res Ctr Sulaymaniyah Iraq Univ Duhok Community & Matern Nursing Unit Duhok Iraq Martin Luther Univ Halle Wittenberg Dept Neurol Halle Germany Al Zaytoonah Univ Jordan Dept Nursing Amman Jordan United Arab Emirates Univ Dept Therapeut Al Ain U Arab Emirates Univ Jordan Coll Pharm Amman Jordan Univ Jordan Dept Biopharmaceut & Clin Pharm Amman Jordan Jhpiego HIV & Infect Dis Dept Abuja Nigeria Adolescent Friendly Res Initiat & Care Dept Adolescent Res & Care Ado Ekiti Nigeria Muhammadiyah Univ Mataram Dept Business Adm Mataram Indonesia Muhammadiyah Univ Mataram Dept Pharm Mataram Indonesia Univ Sharjah Clin Sci Dept Sharjah U Arab Emirates Univ Sharjah Dept Pharm Practice & Pharmacotherapeut Sharjah U Arab Emirates Univ Sharjah Dept Clin Sci Sharjah U Arab Emirates Univ Sharjah Dept Basic Biomed Sci Sharjah U Arab Emirates Univ Sharjah Sharjah Inst Med Sci Sharjah U Arab Emirates Univ Sharjah Coll Med Sharjah U Arab Emirates Kerman Univ Med Sci Dept Med Informat Sci Kerman Iran Kerman Univ Med Sci Dept Immunol Kerman Iran Kerman Un

Background Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020-21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. Methods We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa, respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumonia

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Global pattern, trend, and cross-country inequality of early musculoskeletal disorders from 1990 to 2019, with projection from 2020 to 2050

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MED 2024年第8期5卷 943-962页

作者： Wu, Dongze Jin, Yingzhao Guo, Cui Abbasian, Mohammadreza Abbasifard, Mitra Abbott, J. Haxby Abdullahi, Auwal Abedi, Aidin Abidi, Hassan Abolhassani, Hassan Abu-Gharbieh, Eman Aburuz, Salahdein Abu-Zaid, Ahmed Addo, Isaac Yeboah Adegboye, Oyelola A. Adepoju, Abiola Victor Adikusuma, Wirawan Adnani, Qorinah Estiningtyas Sakilah Aghamiri, Shahin Ahmad, Danish Ahmed, Ayman Aithala, Janardhana P. Akhlaghi, Shiva Akkala, Sreelatha Alalwan, Tariq A. Albashtawy, Mohammed Alemi, Hediyeh Alhalaiqa, Fadwa Alhalaiqa Naji Ali, Endale Alemayehu Almustanyir, Sami Al-Raddadi, Rajaa M. Alvis-Zakzuk, Nelson J. Al-Worafi, Yaser Mohammed Alzahrani, Hosam Alzoubi, Karem H. Amiri, Sohrab Amu, Hubert Amzat, Jimoh Anderson, David B. Anil, Abhishek Antony, Benny Arabloo, Jalal Areda, Damelash Artaman, Al Artamonov, Anton A. Aryal, Krishna K. Asghari-Jafarabadi, Mohammad Ashraf, Tahira Athar, Seyyed Shamsadin Atinafu, Bantalem Tilaye Atout, Maha Moh'd Wahbi Azadnajafabad, Sina Tehrani, Hamed Azhdari Azzam, Ahmed Y. Badawi, Alaa Baghcheghi, Nayereh Bai, Ruhai Baigi, Vali Banach, Maciej Banakar, Morteza Banik, Biswajit Bardhan, Mainak Baernighausen, Till Winfried Barqawi, Hiba Jawdat Barrow, Amadou Bashir, Azadeh Batra, Kavita Bayani, Mojtaba Bayileyegn, Nebiyou Simegnew Begde, Ahmet Beyene, Kebede A. Bhagavathula, Akshaya Srikanth Bhardwaj, Pankaj Bhatt, Gurjit Kaur Bhatti, Jasvinder Singh Bhatti, Rajbir Bijani, Ali Bitra, Veera R. Brazo-Sayavera, Javier Buchbinder, Rachelle Burkart, Katrin Bustanji, Yasser Butt, Muhammad Hammad Camera, Luis Alberto Carvalho, Felix Chattu, Vijay Kumar Chaurasia, Akhilanand Chen, Guangjin Chen, Haowei Chen, Lingxiao Christensen, Steffan Wittrup McPhee Chu, Dinh-Toi Chukwu, Isaac Sunday Comachio, Josielli Cruz-Martins, Natalia Cuschieri, Sarah Dadana, Sriharsha Dadras, Omid Dai, Xiaochen Dai, Zhaoli Das, Saswati Dashti, Mohsen Delgado-Enciso, Ivan Demisse, Biniyam Denova-Gutierrez, Edgar Desye, Belay Dewan, Syed Masudur Rahman Dhingra, Sameer Diress, Mengistie Thanh Chi Do Thao Huynh Phuong Do Khanh Duy Khan Chinese Univ Hong Kong Dept Med & Therapeut Hong Kong Peoples R China Univ Hong Kong Dept Urban Planning & Design Hong Kong Peoples R China Harvard Univ Dept Orthoped Surg Boston MA 02115 USA Shahid Beheshti Univ Med Sci Dept Orthopaed Surg Tehran Iran Rafsanjan Univ Med Sci Dept Internal Med Rafsanjan Iran Rafsanjan Univ Med Sci Clin Res Dev Unit Rafsanjan Iran Univ Otago Otago Med Sch Dept Surg Sci Ctr Musculoskeletal Outcomes Res Dunedin New Zealand Bayero Univ Kano Dept Physiotherapy Kano Nigeria Hong Kong Polytech Univ Dept Rehabil Sci Hong Kong Peoples R China Univ Southern Calif Dept Neurosurg Los Angeles CA 90007 USA Univ Southern Calif Keck Sch Med Los Angeles CA 90007 USA Yasuj Univ Med Sci Lab Technol Sci Dept Yasuj Iran Univ Tehran Med Sci Res Ctr Immunodeficiencies Tehran Iran Karolinska Inst Dept Med Biochem & Biophys Stockholm Sweden Univ Sharjah Dept Clin Sci Sharjah U Arab Emirates United Arab Emirates Univ Dept Therapeut Al Ain U Arab Emirates Univ Jordan Coll Pharm Amman Jordan Alfaisal Univ Dept Surg Riyadh Saudi Arabia Univ Tennessee Coll Grad Hlth Sci Memphis TN USA Univ New S Wales Ctr Social Res Hlth Sydney NSW Australia Canc Inst NSW Qual & Syst Performance Unit Sydney NSW Australia Charles Darwin Univ Menzies Sch Hlth Res Darwin NT Australia HIV & Infect Dis Dept Abuja Nigeria Adolescent Friendly Res Initiat & Care Adolescent Res & Care Ado Ekiti Nigeria Univ Muhammadiyah Mataram Dept Pharm Mataram Indonesia Univ Padjadjaran Fac Med Bandung Indonesia Shahid Beheshti Univ Med Sci Dept Biotechnol Tehran Iran Australian Natl Univ Sch Med & Psychol Canberra ACT Australia Publ Hlth Fdn India Gandhinagar India Univ Khartoum Inst Endem Dis Khartoum Sudan Univ Basel Swiss Trop & Publ Hlth Inst Basel Switzerland Yenepoya Med Coll Dept Orthoped Mangalore India Univ Mississippi Dept Biomol Sci Oxford MS USA Univ Texas Houston Dept Management Policy & Community Hlth Houston TX USA Univ Bahrain

Background: This study aims to estimate the burden, trends, forecasts, and disparities of early musculoskeletal (MSK) disorders among individuals ages 15 to 39 years. Methods: The global prevalence, years lived with disabilities (YLDs), disability-adjusted life years (DALYs), projection, and inequality were estimated for early MSK diseases, including rheumatoid arthritis (RA), osteoarthritis (OA), low back pain (LBP), neck pain (NP), gout, and other MSK diseases (OMSKDs). Findings: More adolescents and young adults were expected to develop MSK disorders by 2050. Across five age groups, the rates of prevalence, YLDs, and DALYs for RA, NP, LBP, gout, and OMSKDs sharply increased from ages 15-19 to 35-39;however, these were negligible for OA before age 30 but increased notably at ages 30-34, rising at least 6- fold by 35-39. The disease burden of gout, LBP, and OA attributable to high BMI and gout attributable to kidney dysfunction increased, while the contribution of smoking to LBP and RA and occupational ergonomic factors to LBP decreased. Between 1990 and 2019, the slope index of inequality increased for six MSK disorders, and the relative concentration index increased for gout, NP, OA, and OMSKDs but decreased for LBP and RA. Conclusions: Multilevel interventions should be initiated to prevent disease burden related to RA, NP, LBP, gout, and OMSKDs among individuals ages 15-19 and toOA among individuals ages 30-34 to tightly control high BMI and kidney dysfunction.

关键词： musculoskeletal disorders Global Burden of Disease study trend inequality pattern rheumatoid arthritis osteoarthritis gout low back pain neck pain Translation to population health

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Corrigendum to "Mixed methods feasibility study for the surviving opioid overdose with naloxone education and resuscitation (SOONER) trial" [Resuscitation Plus 6 (2021) 100131]

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Resuscitation plus 2021年 7卷 100158页

作者： Aaron M Orkin Mercy Charles Kristine Norris Rekha Thomas Leigh Chapman Amy Wright Douglas M Campbell Curtis Handford Michelle Klaiman Shaun Hopkins Rita Shahin Kevin Thorpe Peter Juni Janet Parsons Kate Sellen Nick Goso Richard Hunt Pamela Leece Laurie J Morrison Vicky Stergiopoulos Suzanne Turner Carol Strike Li Ka Shing Knowledge Institute Unity Health Toronto 209 Victoria St Toronto ON M5B 1T8 Canada. Department of Family and Community Medicine University of Toronto 500 University Ave Toronto ON M5G 1V7 Canada. Dalla Lana School of Public Health University of Toronto 155 College St Room 500 Toronto ON M5T 3M7 Canada. Inner City Health Associates 59 Adelaide St E Toronto ON M5C 1K6 Canada. Applied Health Research Centre Li Ka Shing Knowledge Institute Unity Health Toronto 250 Yonge St Toronto ON M5G 1B1 Canada. Population Health & Social Medicine Program University Health Network 101 College St Toronto ON M5G 1L7 Canada. Ryerson University 350 Victoria St Toronto ON M5B 2K3 Canada. Allan Waters Family Simulation Centre Li Ka Shing Knowledge Institute Unity Health Toronto 209 Victoria St. Toronto Ontario M5B 1T8 Canada. Department of Family and Community Medicine St. Michael's Hospital 61 Queen St E #3 Toronto ON M5C 2T2 Canada. Department of Emergency Medicine St. Michael's Hospital 30 Bond St Toronto ON M5B 1X1 Canada. Toronto Public Health 277 Victoria St Toronto ON M5B 2L6 Canada. Design for Health OCAD University 100 McCaul St Toronto ON M5T 1W1 Canada. Public Health Ontario 480 University Ave #300 Toronto ON M5G 1V2 Canada. Centre for Addiction and Mental Health 1000 Queen St W Toronto ON M6J 1H4 Canada.

[This corrects the article DOI: 10.1016/***.2021.100131.].

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Surfactant protein D regulates caspase-8-mediated cascade of the intrinsic pathway of apoptosis while promoting bleb formation

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MOLECULAR IMMUNOLOGY 2017年 92卷 190-198页

作者： Djiadeu, Pascal Farmakovski, Nicole Azzouz, Dhia Kotra, Lakshmi P. Sweezey, Neil Palaniyar, Nades Hosp Sick Children Lung Innate Immun Res Lab Program Translat Med Peter Gilgan Ctr Res & Learning 686 Bay St Toronto ON M5G 0A4 Canada Univ Toronto Leslie Dan Fac Pharm Dept Pharmaceut Sci Toronto ON M5S 3M2 Canada Univ Hlth Network Ctr Mol Design & Prefonnulat Toronto Gen Res Inst 101 Coll St Toronto ON M5G 1L7 Canada Univ Toronto Fac Med Dept Paediat Toronto ON M5G 1X8 Canada Univ Toronto Fac Med Dept Physiol Toronto ON M5G 1X8 Canada Univ Toronto Fac Med Inst Med Sci Toronto ON M5G 1X8 Canada Univ Toronto Fac Med Dept Lab Med Toronto ON M5S 1A8 Canada Univ Toronto Fac Med Dept Pathobiol Toronto ON M5S 1A8 Canada Univ Toronto Fac Med Inst Med Sci Toronto ON M5S 1A8 Canada

Surfactant-associated protein D (SP-D) is a soluble innate immune collectin present on many mucosal surfaces. We recently showed that SP-D suppresses the extrinsic pathway of apoptosis by downregulating caspase-8 activation. However, the effects of SP-D on the intrinsic pathway of apoptosis are not clearly understood. In the intrinsic pathway, cytochrome c is released by mitochondria into the cytoplasm. Oxidation of cytochrome c by cytochrome c oxidase activates the apoptosome and caspase-9 cascade. Both caspase-8- and caspase-9-mediated branches are activated in the intrinsic pathway of apoptosis;however, little is known about the relevance of the caspase-8 pathway in this context. Here we studied the effects of SP-D on different branches of the intrinsic pathway of apoptosis using UV-irradiated Jurkat T-cells. We found that SP-D does not inhibit the caspase-9 branch of apoptosis and the relevance of the caspase-8-related branch became apparent when the caspase-9 pathway was inhibited by blocking cytochrome c oxidase. Under these conditions, SP-D reduces the activation of caspase-8, executioner caspase-3 and exposure of phosphatidylserine (PS) on the membranes of dying cells. By contrast, SP-D increases the formation of nuclear and membrane blebs. Inhibition of caspase-8 confirms the effect of SP-D is unique to the caspase-8 pathway. Overall, SP-D suppresses certain aspects of the intrinsic pathway of apoptosis via reduction of caspase-8 activation and PS flipping while at the same time increasing membrane and nuclear bleb formation. This novel regulatory aspect of SP-D could help to regulate intrinsic pathway of apoptosis to promote effective blebbing and breakdown of dying cells.

关键词： Surfactant protein D Collectins Mucosal surface Intrinsic pathway of apoptosis

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Computer-Based Driving in Dementia Decision Tool With Mail Support: Cluster Randomized Controlled Trial

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JOURNAL OF MEDICAL INTERNET RESEARCH 2018年第5期20卷 e194-e194页

作者： Rapoport, Mark J. Sarracini, Carla Zucchero Kiss, Alex Lee, Linda Byszewski, Anna Seitz, Dallas P. Vrkljan, Brenda Molnar, Frank Herrmann, Nathan Tang-Wai, David F. Frank, Christopher Henry, Blair Pimlott, Nicholas Masellis, Mario Naglie, Gary Sunnybrook Hlth Sci Ctr Dept Psychiat 2075 Bayview Ave Toronto ON M4N 3M5 Canada Univ Toronto Dept Psychiat Toronto ON Canada Sunnybrook Res Inst Dept Res Design & Biostat Toronto ON Canada Univ Toronto Inst Hlth Policy Management & Evaluat Toronto ON Canada McMaster Univ Dept Family Med Hamilton ON Canada Ottawa Hosp Div Geriatr Med Ottawa ON Canada Univ Ottawa Div Geriatr Med Ottawa ON Canada Providence Care Seniors Mental Hlth Program Kingston ON Canada Queens Univ Dept Psychiat Kingston ON Canada McMaster Univ Sch Rehabil Sci Hamilton ON Canada Univ Hlth Network Memory Clin Toronto ON Canada Univ Toronto Div Geriatr Med Div Neurol Toronto ON Canada Providence Care Specialized Geriatr Serv Kingston ON Canada Queens Univ Div Geriatr Med Kingston ON Canada Sunnybrook Hlth Sci Ctr Clin Eth Ctr Toronto ON Canada Univ Toronto Dept Family & Community Med Toronto ON Canada Womens Coll Hosp Dept Family & Community Med Toronto ON Canada Sunnybrook Hlth Sci Ctr Dept Med Toronto ON Canada Univ Toronto Div Neurol Toronto ON Canada Baycrest Hlth Sci Dept Med Toronto ON Canada Univ Toronto Div Geriatr Med Toronto ON Canada

Background: Physicians often find significant challenges in assessing automobile driving in persons with mild cognitive impairment and mild dementia and deciding when to report to transportation administrators. Care must be taken to balance the safety of patients and other road users with potential negative effects of issuing such reports. Objective: The aim of this study was to assess whether a computer-based Driving in Dementia Decision Tool (DD-DT) increased appropriate reporting of patients with mild dementia or mild cognitive impairment to transportation administrators. Methods: The study used a parallel-group cluster nonblinded randomized controlled trial design to test a multifaceted knowledge translation intervention. The intervention included a computer-based decision support system activated by the physician-user, which provides a recommendation about whether to report patients with mild dementia or mild cognitive impairment to transportation administrators, based on an algorithm derived from earlier work. The intervention also included a mailed educational package and Web-based specialized reporting forms. Specialists and family physicians with expertise in dementia or care of the elderly were stratified by sex and randomized to either use the DD-DT or a control version of the tool that required identical data input as the intervention group, but instead generated a generic reminder about the reporting legislation in Ontario, Canada. The trial ran from September 9, 2014 to January 29, 2016, and the primary outcome was the number of reports made to the transportation administrators concordant with the algorithm. Results: A total of 69 participating physicians were randomized, and 36 of these used the DD-DT;20 of the 35 randomized to the intervention group used DD-DT with 114 patients, and 16 of the 34 randomized to the control group used it with 103 patients. The proportion of all assessed patients reported to the transportation administrators concordant w

关键词： dementia mild cognitive impairment automobile driving decision support systems clinical

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Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021

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LANCET 2024年第10440期403卷 2133-2161页

作者： Ferrari, Alize J. Santomauro, Damian Francesco Aali, Amirali Abate, Yohannes Habtegiorgis Abbafati, Cristiana Abbastabar, Hedayat ElHafeez, Samar Abd Abdelmasseh, Michael Abd-Elsalam, Sherief Abdollahi, Arash Abdullahi, Auwal Abegaz, Kedir Hussein Zuniga, Roberto Ariel Abeldano Aboagye, Richard Gyan Abolhassani, Hassan Abreu, Lucas Guimaraes Abualruz, Hasan Abu-Gharbieh, Eman Abu-Rmeileh, Niveen M. E. Ackerman, Ilana N. Addo, Isaac Yeboah Addolorato, Giovanni Adebiyi, Akindele Olupelumi Adepoju, Abiola Victor Adewuyi, Habeeb Omoponle Afyouni, Shadi Afzal, Saira Afzal, Sina Agodi, Antonella Ahmad, Aqeel Ahmad, Danish Ahmad, Firdos Ahmad, Shahzaib Ahmed, Ali Ahmed, Luai A. Ahmed, Muktar Beshir Ajami, Marjan Akinosoglou, Karolina Akkaif, Mohammed Ahmed Al Hasan, Syed Mahfuz Alalalmeh, Samer O. Al-Aly, Ziyad Albashtawy, Mohammed Aldridge, Robert W. Alemu, Meseret Desalegn Alemu, Yihun Mulugeta Alene, Kefyalew Addis Al-Gheethi, Adel Ali Saeed Alharrasi, Maryam Alhassan, Robert Kaba Ali, Mohammed Usman Ali, Rafat Ali, Syed Shujait Shujait Alif, Sheikh Mohammad Aljunid, Syed Mohamed Al-Marwani, Sabah Almazan, Joseph Uy Alomari, Mahmoud A. Al-Omari, Basem Altaany, Zaid Alvis-Guzman, Nelson Alvis-Zakzuk, Nelson J. Alwafi, Hassan Al-Wardat, Mohammad Sami Al-Worafi, Yaser Mohammed Aly, Safwat Alzoubi, Karem H. Amare, Azmeraw T. Amegbor, Prince M. Ameyaw, Edward Kwabena Amin, Tarek Tawfik Amindarolzarbi, Alireza Amiri, Sohrab Amugsi, Dickson A. Ancuceanu, Robert Anderlini, Deanna Anderson, David B. Andrade, Pedro Prata Andrei, Catalina Liliana Ansari, Hossein Antony, Catherine M. Anwar, Saleha Anwar, Sumadi Lukman Anwer, Razique Anyanwu, Philip Emeka Arab, Juan Pablo Arabloo, Jalal Arafat, Mosab Araki, Daniel T. Aravkin, Aleksandr Y. Arkew, Mesay Armocida, Benedetta Arndt, Michael Benjamin Arooj, Mahwish Artamonov, Anton A. Aruleba, Raphael Taiwo Arumugam, Ashokan Ashbaugh, Charlie Ashemo, Mubarek Yesse Ashraf, Muhammad Asika, Marvellous O. Askari, Elaheh Astell-Burt, Thomas Athari, Seyyed Shamsadin Atorkey, Prince Atout, Ma Univ Washington Inst Hlth Metr & Evaluat Seattle WA 98195 USA Univ Queensland Sch Publ Hlth Brisbane Qld Australia Univ Queensland Ctr Sensorimotor Performance Brisbane Qld Australia Univ Queensland Dept Urol Brisbane Qld Australia Univ Queensland Sch Hlth & Rehabil Sci Brisbane Qld Australia Univ Queensland Sch Dent Brisbane Qld Australia Univ Queensland Queensland Brain Inst Brisbane Qld Australia Univ Washington Dept Appl Math Seattle WA USA Univ Washington Dept Hlth Metr Sci Sch Med Seattle WA USA Univ Washington Dept Global Hlth Seattle WA USA Univ Washington Dept Hlth Syst & Populat Hlth Seattle WA USA Univ Washington Dept Family Med Seattle WA USA Univ Washington Div Pediat Hematol Oncol Seattle WA USA Univ Washington Dept Neurol Seattle WA USA Univ Washington Dept Anesthesiol & Pain Med Seattle WA USA Univ Washington Div Plast & Reconstruct Surg Seattle WA USA Univ Washington Henry M Jackson Sch Int Studies Seattle WA USA Queensland Ctr Mental Hlth Res Policy & Epidemiol Grp Wacol Qld Australia Queensland Ctr Mental Hlth Res West Moreton Hosp Hlth Serv Wacol Qld Australia Mashhad Univ Med Sci Fac Med Mashhad Razavi Khorasan Iran Mashhad Univ Med Sci Dent Res Ctr Mashhad Razavi Khorasan Iran Mashhad Univ Med Sci Dept Orthodont Mashhad Razavi Khorasan Iran Mashhad Univ Med Sci Clin Res Dev Unit Mashhad Razavi Khorasan Iran Aleta Wondo Hosp Dept Clin Governance & Qual Improvement Aleta Wondo Ethiopia Univ Roma La Sapienza Dept Jurid & Econ Studies Rome Italy Univ Roma La Sapienza Dept Publ Hlth & Infect Dis Rome Italy Univ Tehran Med Sci Adv Diagnost & Intervent Radiol Res Ctr Tehran Iran Univ Tehran Med Sci Res Ctr Immunodeficiencies Tehran Iran Univ Tehran Med Sci Noncommunicable Dis Res Ctr Tehran Iran Univ Tehran Med Sci Sch Med Tehran Iran Univ Tehran Med Sci Iranian Res Ctr HIV AIDS Tehran Iran Univ Tehran Med Sci Cardiac Primary Prevent Res Ctr Tehran Iran Univ Tehran Med Sci Dept Cardiac Elec

Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 9

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Multiculturalism and Diversity in the Industry: Black designers Speak Out

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design Management Review 2017年第2期28卷

作者： Meshella Eddye Woods Holds a BA in human environment and design and has 39 years of experience in interior architectural design and facility management. Her career has included performance and supervision as well as training evaluation and management of work involved in the planning design and construction of interior environments in private industry and the federal government. She offers additional expertise in computer technology as it relates to project planning and documentation program management and administration video and digital media and website design. Woods has been acknowledged for award‐winning project work and for reviewing analyzing implementing and maintaining government and private industry design programs projects budgets and collateral duties with national effects. Her active involvement as founding member and board member of various design organizations has allowed her to bring together a network of designers educators and students to participate in meaningful programs events and projects that endeavor to improve the future of our youth our profession and underserved communities in our nation and the world.

A celebration of accomplished designers and design managers whose success against “lack of diversity” obstacles enables giving back to their communities and mentoring those who are waiting in the wings. A celebration of designers and design managers who are succeeding despite the odds, giving back to their communities, and mentoring those who are waiting in the wings.

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A saturated map of common genetic variants associated with human height

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NATURE 2022年第7933期610卷 704-+页

作者： Yengo, Loic Vedantam, Sailaja Marouli, Eirini Sidorenko, Julia Bartell, Eric Sakaue, Saori Graff, Marielisa Eliasen, Anders U. Jiang, Yunxuan Raghavan, Sridharan Miao, Jenkai Arias, Joshua D. Graham, Sarah E. Mukamel, Ronen E. Spracklen, Cassandra N. Yin, Xianyong Chen, Shyh-Huei Ferreira, Teresa Highland, Heather H. Ji, Yingjie Karaderi, Tugce Lin, Kuang Lull, Kreete Malden, Deborah E. Medina-Gomez, Carolina Machado, Moara Moore, Amy Rueger, Sina Sim, Xueling Vrieze, Scott Ahluwalia, Tarunveer S. Akiyama, Masato Allison, Matthew A. Alvarez, Marcus Andersen, Mette K. Ani, Alireza Appadurai, Vivek Arbeeva, Liubov Bhaskar, Seema Bielak, Lawrence F. Bollepalli, Sailalitha Bonnycastle, Lori L. Bork-Jensen, Jette Bradfield, Jonathan P. Bradford, Yuki Braund, Peter S. Brody, Jennifer A. Burgdorf, Kristoffer S. Cade, Brian E. Cai, Hui Cai, Qiuyin Campbell, Archie Canadas-Garre, Marisa Catamo, Eulalia Chai, Jin-Fang Chai, Xiaoran Chang, Li-Ching Chang, Yi-Cheng Chen, Chien-Hsiun Chesi, Alessandra Choi, Seung Hoan Chung, Ren-Hua Cocca, Massimiliano Concas, Maria Pina Couture, Christian Cuellar-Partida, Gabriel Danning, Rebecca Daw, E. Warwick Degenhard, Frauke Delgado, Graciela E. Delitala, Alessandro Demirkan, Ayse Deng, Xuan Devineni, Poornima Dietl, Alexander Dimitriou, Maria Dimitrov, Latchezar Dorajoo, Rajkumar Ekici, Arif B. Engmann, Jorgen E. Fairhurst-Hunter, Zammy Farmaki, Aliki-Eleni Faul, Jessica D. Fernandez-Lopez, Juan-Carlos Forer, Lukas Francescatto, Margherita Freitag-Wolf, Sandra Fuchsberger, Christian Galesloot, Tessel E. Gao, Yan Gao, Zishan Geller, Frank Giannakopoulou, Olga Giulianini, Franco Gjesing, Anette P. Goel, Anuj Gordon, Scott D. Gorski, Mathias Grove, Jakob Guo, Xiuqing Gustafsson, Stefan Haessler, Jeffrey Hansen, Thomas F. Havulinna, Aki S. Haworth, Simon J. He, Jing Heard-Costa, Nancy Hebbar, Prashantha Hindy, George Ho, Yuk-Lam A. Hofer, Edith Holliday, Elizabeth Horn, Katrin Hornsby, Whitney E. Hottenga, Jouke-Jan Huang, Hongyan Huang, Jie Huerta-Chagoya, Alicia Huffman, Jennifer E. Hung Univ Queensland Inst Mol Biosci Brisbane Qld Australia Boston Childrens Hosp Div Endocrinol Boston MA 02115 USA Broad Inst MIT & Harvard Program Med & Populat Genet Cambridge MA 02142 USA Queen Mary Univ London Barts & London Sch Med & Dent William Harvey Res Inst London England Harvard Med Sch Boston MA 02115 USA RIKEN Ctr Integrat Med Sci Lab Stat Anal Yokohama Kanagawa Japan Osaka Univ Dept Stat Genet Grad Sch Med Osaka Japan Brigham & Womens Hosp Div Genet 75 Francis St Boston MA 02115 USA Brigham & Womens Hosp Div Rheumatol 75 Francis St Boston MA 02115 USA Harvard Med Sch Dept Med Boston MA 02115 USA Univ North Carolina Chapel Hill Dept Epidemiol Gillings Sch Global Publ Hlth Chapel Hill NC USA Univ Copenhagen Herlev & Gentofte Hosp Copenhagen Prospect Studies Asthma Childhood COPSAC Copenhagen Denmark Tech Univ Denmark Dept Hlth Technol Sect Bioinformat Copenhagen Denmark 23AndMe Sunnyvale CA USA Eastern Colorado Healthcare Syst Dept Vet Affairs Aurora CO USA Univ Colorado Div Biomed Informat & Personalized Med Anschutz Med Campus Aurora CO USA NCI Div Canc Epidemiol & Genet Rockville MD USA Univ Michigan Dept Internal Med Div Cardiol Ann Arbor MI 48109 USA Brigham & Womens Hosp Dept Med Div Genet 75 Francis St Boston MA 02115 USA Univ North Carolina Chapel Hill Dept Genet Chapel Hill NC USA Univ Massachusetts Dept Biostat & Epidemiol Sch Publ Hlth & Hlth Sci Amherst MA USA Univ Michigan Sch Publ Hlth Dept Biostat Ann Arbor MI 48109 USA Univ Michigan Sch Publ Hlth Ctr Stat Genet Ann Arbor MI 48109 USA Wake Forest Sch Med Dept Biostat & Data Sci Winston Salem NC 27101 USA Univ Oxford Li Ka Shing Ctr Hlth Informat & Discovery Big Data Inst Oxford England Univ Exeter Coll Med & Hlth Genet Complex Traits Exeter Devon England Univ Copenhagen Fac Hlth & Med Sci Ctr Hlth Data Sci Copenhagen Denmark Univ Oxford Wellcome Ctr Human Genet Nuffield Dept Med Oxford England Univ Oxford Nuffield Dept Populat Hlth Oxf

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries. A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

关键词： Genetic markers Genome-wide association studies Quantitative trait

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Mapping the human genetic architecture of COVID-19

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NATURE 2021年第7889期600卷 472-+页

作者： Niemi, Mari E. K. Karjalainen, Juha Daly, Mark Ganna, Andrea Mehtonen, Juha Cordioli, Mattia Kaunisto, Mari Pigazzini, Sara Donner, Kati Kivinen, Katja Palotie, Aarno Daly, Mark J. Liao, Rachel G. Kanai, Masahiro Veerapen, Kumar Minica, Camelia Trankiem, Amy Balaconis, Mary K. Nguyen, Huy Solomonson, Matthew Francioli, Laurent Wang, Qingbo Green, Robert C. Bryant, Sam Finucane, Hilary Martin, Alicia R. Zhou, Wei Nkambule, Lindokuhle Karczewski, Konrad J. Atkinson, Elizabeth G. Tsuo, Kristin Baya, Nikolas Turley, Patrick Gupta, Rahul Walters, Raymond K. Palmer, Duncan S. Sarma, Gopal Cheng, Nathan Lu, Wenhan Churchhouse, Claire Goldstein, Jacqueline, I King, Daniel Seed, Cotton Neale, Benjamin M. Satterstrom, F. Kyle Pathak, Gita A. Wendt, Frank R. Polimanti, Renato Andrews, Shea J. Sloofman, Laura Sealfon, Stuart C. Fernandez-Cadenas, Israel Schulte, Eva C. Protzer, Ulrike Striano, Pasquale Coviello, Domenico A. Zara, Federico Salpietro, Vincenzo Iacomino, Michele Scudieri, Paolo Bocciardi, Renata Minetti, Carlo Vari, Maria Stella Madia, Francesca Marouli, Eirini Kanoni, Stavroula Moutsianas, Loukas Karim, Mohd Anisul Ghoussaini, Maya Schwartzentruber, Jeremy Dunham, Ian Savage, Jeanne Posthuma, Danielle Tissink, Elleke Uffelmann, Emil Butler-Laporte, Guillaume Richards, J. Brent Nakanishi, Tomoko Morrison, David R. Forgetta, Vincenzo Ghosh, Biswarup Laurent, Laetitia Henry, Danielle Abdullah, Tala Adeleye, Olumide Mamlouk, Noor Kimchi, Nofar Afrasiabi, Zaman Rezk, Nardin Vulesevic, Branka Bouab, Meriem Guzman, Charlotte Petitjean, Louis Tselios, Chris Xue, Xiaoqing Afilalo, Jonathan Adra, Darin Kim, Han-Na Okada, Yukinori Byun, Jinyoung Han, Younghun Uddin, Mohammed Jashim Smith, George Davey Willer, Cristen J. Buxbaum, Joseph D. Sloofman, Laura G. Collins, Brett L. Levy, Tess Underwood, Slayton J. Britvan, Bari Keller, Katherine Tang, Lara Peruggia, Michael Hiester, Liam L. Niblo, Kristi Aksentijevich, Alexandra Labkowsky, Alexander Karp, Avromie Zlatopolsky, Menachem Arora, Jatin Raychaudhuri, Soumya Mercader, Univ Helsinki Inst Mol Med Finland FIMM Helsinki Finland Broad Inst MIT & Harvard Cambridge MA 02142 USA Massachusetts Gen Hosp Analyt & Translat Genet Unit Boston MA 02114 USA Massachusetts Gen Hosp Broad Inst MIT & Harvard Cambridge MA USA Yale Univ New Haven CT USA Icahn Sch Med Mt Sinai New York NY USA St Pau Hosp Biomed Res Inst St Pau IIB St Pau Stroke Pharmacogen & Genet Inmungen CoV2 Barcelona Spain Tech Univ Munich Inst Virol Munich Germany Helmholtz Zentrum Munchen Munich Germany Univ Munich Inst Psychiat Phen & Genom Med Ctr Munich Germany Univ Munich Dept Psychiat Med Ctr Munich Germany Ist Giannina Gaslini IRCCS Genoa Italy Univ Genoa Dept Neurosci Rehabil Ophthalmol Genet Maternar & Genoa Italy Queen Mary Univ London London England Open Targets Wellcome Genome Campus Hinxton England Vrije Univ Amsterdam Ctr Neurogen & Cognit Res Amsterdam Neurosci Dept Complex Trait Genet Amsterdam Netherlands McGill Univ Jewish Gen Hosp Lady Davis Inst Montreal PQ Canada Sungkyunkwan Univ Kangbuk Samsung Hosp Med Res Inst Sch Med Suwon South Korea Osaka Univ Grad Sch Med Osaka Japan Baylor Coll Med Houston TX 77030 USA Mohammed Bin Rashid Univ Med & Hlth Sci Dubai U Arab Emirates Univ Bristol MRC Integrat Epidemiol Unit IEU Bristol Avon England Michigan Med Div Cardiovasc Med Dept Internal Med Ann Arbor MI USA Univ Michigan Dept Human Genet Med Sch Ann Arbor MI 48109 USA Univ Michigan Dept Computat Med & Bioinformat Med Sch Ann Arbor MI 48109 USA Icahn Sch Med Mt Sinai Dept Psychiat Seaver Autism Ctr Res & Treatment New York NY 10029 USA Broad Inst MIT & Harvard Program Med & Populat Genet Cambridge MA 02142 USA Univ Calif Los Angeles David Geffen Sch Med Los Angeles CA 90095 USA Inst Pasteur Paris France Harvard Sch Publ Hlth Boston MA USA Univ Queensland Inst Mol Biosci Brisbane Qld Australia Wellcome Sanger Inst Wellcome Genome Campus Hinxton England European Bioinformat Inst EMBL EBI European Mol Biol Lab We

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19(1,2), host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases(3-7). They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

关键词： Genetics Genome-wide association studies SARS-CoV-2 Viral infection Science Humanities and Social Sciences multidisciplinary

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