Discovery of Northern Fur Seals (Callorhinus ursinus) Breeding on Bogoslof Island Southeastern Bering Sea

A small group of northern fur seals (Callorhinus ursinus) including one male with two females, each with a small pup, and two lone males were discovered on Bogoslof Island, Alaska in the Bering Sea on 20 July 1980. This is the first evidence of breeding on Bogoslof, or on any island in the eastern Bering Sea other than the Pribilof Islands. We suggest that these fur seals require breeding islands adjacent to the continental shelf break where they are supported by the pelagic food web characteristic of the oceanic and outer shelf domains.Key words: fur seal, Callorhinus ursinus, Steller sea lion, Eumetopias jubatus, Aleutian Islands, Bering SeaMots clés: otarie à fourrure, Callorhinus ursinus, otarie, Eumetopias jubatus, îles Aléoutiennes, mer de Bérin

Amino Acid Substitutions in the S2 Subunit of Mouse Hepatitis Virus Variant V51 Encode Determinants of Host Range Expansion

We previously described mouse hepatitis virus (MHV) variant V51 derived from a persistent infection of murine DBT cells with an expanded host range (R. S. Baric, E. Sullivan, L. Hensley, B. Yount, and W. Chen, J. Virol. 73:638-649, 1999). Sequencing of the V51 spike gene, the mediator of virus entry, revealed 13 amino acid substitutions relative to the originating MHV A59 strain. Seven substitutions were located in the amino-terminal S1 cleavage subunit, and six were located in the carboxy-terminal S2 cleavage subunit. Using targeted RNA recombination, we constructed a panel of recombinant viruses to map the mediators of host range to the six substitutions in S2, with a subgroup of four changes of particular interest. This subgroup maps to two previously identified domains within S2, a putative fusion peptide and a heptad repeat, both conserved features of class I fusion proteins. In addition to an altered host range, V51 displayed altered utilization of CEACAM1a, the high-affinity receptor for A59. Interestingly, a recombinant with S1 from A59 and S2 from V51 was severely debilitated in its ability to productively infect cells via CEACAM1a, while the inverse recombinant was not. This result suggests that the S2 substitutions exert powerful effects on the fusion trigger that normally passes from S1 to S2. These novel findings play against the existing data that suggest that MHV host range determinants are located in the S1 subunit, which harbors the receptor binding domain, or involve coordinating changes in both S1 and S2. Mounting evidence also suggests that the class I fusion mechanism may possess some innate plasticity that regulates viral host range

Biogeochemical Analysis of Ancient Pacific Cod Bone Suggests Hg Bioaccumulation was Linked to Paleo Sea Level Rise and Climate Change

Deglaciation at the end of the Pleistocene initiated major changes in ocean circulation and distribution. Within a brief geological time, large areas of land were inundated by sea-level rise and today global sea level is 120 m above its minimum stand during the last glacial maximum. This was the era of modern sea shelf formation; climate change caused coastal plain flooding and created broad continental shelves with innumerable consequences to marine and terrestrial ecosystems and human populations. In Alaska, the Bering Sea nearly doubled in size and stretches of coastline to the south were flooded, with regional variability in the timing and extent of submergence. Here we suggest how past climate change and coastal flooding are linked to mercury bioaccumulation that could have had profound impacts on past human populations and that, under conditions of continued climate warming, may have future impacts. Biogeochemical analysis of total mercury (tHg) and δ13C/δ15N ratios in the bone collagen of archeologically recovered Pacific Cod (Gadus macrocephalus) bone shows high levels of tHg during early/mid-Holocene. This pattern cannot be linked to anthropogenic activity or to food web trophic changes, but may result from natural phenomena such as increases in productivity, carbon supply and coastal flooding driven by glacial melting and sea-level rise. The coastal flooding could have led to increased methylation of Hg in newly submerged terrestrial land and vegetation. Methylmercury is bioaccumulated through aquatic food webs with attendant consequences for the health of fish and their consumers, including people. This is the first study of tHg levels in a marine species from the Gulf of Alaska to provide a time series spanning nearly the entire Holocene and we propose that past coastal flooding resulting from climate change had the potential to input significant quantities of Hg into marine food webs and subsequently to human consumers

Real-world treatment patterns and effectiveness of palbociclib plus an aromatase inhibitor in patients with metastatic breast cancer aged 75 years or older

BackgroundElderly patients are generally underrepresented in oncology clinical trials; therefore, real-world data are needed to inform clinical management of elderly patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) metastatic breast cancer (mBC). This subanalysis of the P-REALITY X study (NCT05361655) evaluated palbociclib treatment patterns and comparative effectiveness of palbociclib plus an aromatase inhibitor (AI) versus an AI alone among patients with HR+/HER2− mBC aged ≥ 75 years treated in routine clinical practice in the United States.MethodsThis retrospective observational cohort study used electronic health records from the Flatiron Health Analytic Database. Palbociclib treatment patterns, overall survival (OS), real-world progression-free survival (rwPFS), and time to chemotherapy (TTC) were evaluated. Three methods were used for comparative analyses: (1) an unadjusted analysis, (2) stabilized inverse probability treatment weighting (sIPTW; primary analysis), and (3) propensity score matching (PSM; sensitivity analysis).ResultsA total of 961 patients aged ≥ 75 years with HR+/HER2− mBC were identified who started palbociclib plus an AI (n = 313) or an AI alone (n = 648) as first-line (1L) therapy between February 2015 and March 2020 (data cut-off: September 30, 2020). Among patients in the palbociclib plus an AI group with a documented palbociclib starting dose (n = 306), approximately 75% started palbociclib at 125 mg/day, and approximately 40% experienced dose adjustment. After sIPTW, patients treated with palbociclib plus an AI versus an AI alone had significantly improved OS (median of 43.0 vs. 32.4 months; hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.51–0.84]; P = 0.0007), rwPFS (median of 20.0 vs. 15.0 months; HR, 0.72 (0.59–0.89); P = 0.0021), and TTC (median of 40.2 vs. 27.4 months; HR, 0.69 [0.55–0.87]; P = 0.0014). These significant improvements in OS, rwPFS, and TTC remained consistent in the unadjusted analysis and after PSM.ConclusionThis real-world comparative analysis demonstrated that 1L palbociclib plus an AI is associated with improved effectiveness compared with an AI alone among patients with HR+/HER2− mBC aged ≥ 75 years. These findings support palbociclib plus an AI as a standard-of-care 1L treatment for elderly patients with HR+/HER2− mBC

Incidence of insulin-requiring diabetes in the US military

The aim of the study was to determine age- and race-related, and overall incidence rates of insulin-requiring diabetes in adults in the US military. Electronic records for admissions to US military and Tricare hospitals during 1990–2005 and visits to military clinics during 2000–2005 were identified using the Career History Archival Medical and Personnel System at the Naval Health Research Center, San Diego, CA, USA. Population data were obtained from the Defense Manpower Data Center and Defense Medical Epidemiology Database. In men there were 2,918 new cases of insulin-requiring diabetes in 20,427,038 person-years at ages 18–44 years (median age 28 years) for a total age-adjusted incidence rate of 17.5 per 100,000 person-years (95% CI 16.4–18.6). Incidence rates were twice as high in black men as in white men (31.5 vs 14.5 per 100,000, p < 0.001). In women there were 414 new cases in 3,285,000 person-years at ages 18–44 years (median age 27 years), for a total age-adjusted incidence rate of 13.6 per 100,000 (95% CI 12.4–14.9). Incidence rates were twice as high in black women as in white women (21.8 vs 9.7 per 100,000, p < 0.001). In a regression model, incidence of insulin-requiring diabetes peaked annually in the winter–spring season (OR 1.46, p < 0.01). Race and seasonal differences persisted in the multivariate analysis. Differences in incidence rates by race and season suggest a need for further research into possible reasons, including the possibility of a contribution from vitamin D deficiency. Cohort studies using prediagnostic serum 25-hydroxyvitamin D should be conducted to further evaluate this relationship

Policy Recommendations for Meeting the Grand Challenge to Achieve Equal Opportunity and Justice

This brief was created forSocial Innovation for America’s Renewal, a policy conference organized by the Center for Social Development in collaboration with the American Academy of Social Work & Social Welfare, which is leading theGrand Challenges for Social Work initiative to champion social progress. The conference site includes links to speeches, presentations, and a full list of the policy briefs

Overall survival results from the randomized phase 2 study of palbociclib in combination with letrozole versus letrozole alone for first‑line treatment of ER+/HER2− advanced breast cancer (PALOMA‑1, TRIO‑18)

Purpose Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, approved in combination with endocrine therapy for the treatment of women and men with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC). In the phase 2, open-label, PALOMA-1 trial, palbociclib plus letrozole signifcantly prolonged progression-free survival (PFS) versus letrozole alone (hazard ratio, 0.488; 95% CI 0.319‒0.748; P=0.0004; median PFS, 20.2 vs 10.2 months, respectively) in postmenopausal women with estrogen receptor–positive (ER+)/HER2− ABC. Here, we present the fnal overall survival (OS) and updated safety results. Methods Postmenopausal women with ER+/HER2− ABC were randomized 1:1 to receive either palbociclib (125 mg/day, 3/1 schedule) plus letrozole (2.5 mg/day, continuous) or letrozole alone (2.5 mg/day, continuous). The primary endpoint was investigator-assessed PFS; secondary endpoints included OS and safety. Results A total of 165 patients were randomized. At the data cutof date of December 30, 2016 (median duration of follow-up, 64.7 months), the stratifed hazard ratio for OS was 0.897 (95% CI 0.623–1.294; P=0.281); median OS in the palbociclib plus letrozole and letrozole alone arms was 37.5 and 34.5 months, respectively. The median time from randomization to frst subsequent chemotherapy use was longer with palbociclib plus letrozole than letrozole alone (26.7 and 17.7 months, respectively). The most frequently reported adverse event in the palbociclib plus letrozole arm was neutropenia (any grade, 75%; grade 3 or 4, 59%). Conclusions Palbociclib plus letrozole treatment led to a numerical but not statistically signifcant improvement in median OS. Pfzer Inc (NCT00721409

Making effective use of healthcare data using data-to-text technology

Healthcare organizations are in a continuous effort to improve health outcomes, reduce costs and enhance patient experience of care. Data is essential to measure and help achieving these improvements in healthcare delivery. Consequently, a data influx from various clinical, financial and operational sources is now overtaking healthcare organizations and their patients. The effective use of this data, however, is a major challenge. Clearly, text is an important medium to make data accessible. Financial reports are produced to assess healthcare organizations on some key performance indicators to steer their healthcare delivery. Similarly, at a clinical level, data on patient status is conveyed by means of textual descriptions to facilitate patient review, shift handover and care transitions. Likewise, patients are informed about data on their health status and treatments via text, in the form of reports or via ehealth platforms by their doctors. Unfortunately, such text is the outcome of a highly labour-intensive process if it is done by healthcare professionals. It is also prone to incompleteness, subjectivity and hard to scale up to different domains, wider audiences and varying communication purposes. Data-to-text is a recent breakthrough technology in artificial intelligence which automatically generates natural language in the form of text or speech from data. This chapter provides a survey of data-to-text technology, with a focus on how it can be deployed in a healthcare setting. It will (1) give an up-to-date synthesis of data-to-text approaches, (2) give a categorized overview of use cases in healthcare, (3) seek to make a strong case for evaluating and implementing data-to-text in a healthcare setting, and (4) highlight recent research challenges.Comment: 27 pages, 2 figures, book chapte