Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Anticipating and Adapting to the Future Impacts of Climate Change on the Health, Security and Welfare of Low Elevation Coastal Zone (LECZ) Communities in Southeastern USA

Low elevation coastal zones (LECZ) are extensive throughout the southeastern United States. LECZ communities are threatened by inundation from sea level rise, storm surge, wetland degradation, land subsidence, and hydrological flooding. Communication among scientists, stakeholders, policy makers and minority and poor residents must improve. We must predict processes spanning the ecological, physical, social, and health sciences. Communities need to address linkages of (1) human and socioeconomic vulnerabilities; (2) public health and safety; (3) economic concerns; (4) land loss; (5) wetland threats; and (6) coastal inundation. Essential capabilities must include a network to assemble and distribute data and model code to assess risk and its causes, support adaptive management, and improve the resiliency of communities. Better communication of information and understanding among residents and officials is essential. Here we review recent background literature on these matters and offer recommendations for integrating natural and social sciences. We advocate for a cyber-network of scientists, modelers, engineers, educators, and stakeholders from academia, federal state and local agencies, non-governmental organizations, residents, and the private sector. Our vision is to enhance future resilience of LECZ communities by offering approaches to mitigate hazards to human health, safety and welfare and reduce impacts to coastal residents and industries

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are 500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p