Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).

Persistent low prevalence of hepatitis B vaccination among people with HIV: Time for a change?

Hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma and mortality among people living with HIV (PLWH). HBV vaccination provides protection from infection; however, vaccination rates are low. We conducted a retrospective analysis at three HIV centres in Texas to determine the proportion of PLWH who received the recommended 3 doses of hepatitis B vaccine within 1 year. Factors associated with vaccination completion were explored. In our sample of three sites in a state with high HIV transmission and high rates of liver disease from 2011 to 2021, showed low rates of hepatitis B vaccination. Among eligible PLWH, only 9% completed the 3-dose hepatitis B vaccine series in 1 year. There is an urgent need to improve HBV vaccination to reach 2030 target for hepatitis B elimination.

Red-list status and extinction risk of the world's whales, dolphins, and porpoises.

To understand the scope and scale of the loss of biodiversity, tools are required that can be applied in a standardized manner to all species globally, spanning realms from land to the open ocean. We used data from the International Union for the Conservation of Nature Red List to provide a synthesis of the conservation status and extinction risk of cetaceans. One in 4 cetacean species (26% of 92 species) was threatened with extinction (i.e., critically endangered, endangered, or vulnerable) and 11% were near threatened. Ten percent of cetacean species were data deficient, and we predicted that 2-3 of these species may also be threatened. The proportion of threatened cetaceans has increased: 15% in 1991, 19% in 2008, and 26% in 2021. The assessed conservation status of 20% of species has worsened from 2008 to 2021, and only 3 moved into categories of lesser threat. Cetacean species with small geographic ranges were more likely to be listed as threatened than those with large ranges, and those that occur in freshwater (100% of species) and coastal (60% of species) habitats were under the greatest threat. Analysis of odontocete species distributions revealed a global hotspot of threatened small cetaceans in Southeast Asia, in an area encompassing the Coral Triangle and extending through nearshore waters of the Bay of Bengal, northern Australia, and Papua New Guinea and into the coastal waters of China. Improved management of fisheries to limit overfishing and reduce bycatch is urgently needed to avoid extinctions or further declines, especially in coastal areas of Asia, Africa, and South America.

Estado en la lista roja y riesgo de extinción de las ballenas, delfines y marsopas del mundo Resumen Para comprender el alcance y la escala de la pérdida de biodiversidad, se necesitan herramientas que puedan aplicarse de forma estandarizada a todas las especies a nivel mundial y que abarquen todos los ámbitos desde la tierra hasta el océano. Utilizamos datos de la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza para proporcionar una síntesis del estado de conservación y el riesgo de extinción de los cetáceos. Una de cada 4 especies de cetáceos (26% de 92 especies) se encuentra amenazada (es decir, en peligro crítico, en peligro o vulnerable) y el 11% de las especies está clasificado como casi amenazada. El 10% de las especies de cetáceos carecía de datos, por lo que predijimos que 2-3 de estas especies también podrían estar amenazadas. La proporción de cetáceos amenazados ha aumentado: 15% en 1991, 19% en 2008 y 26% en 2021. El estado de conservación evaluado del 20% de las especies ha empeorado de 2008 a 2021, pues sólo 3 pasaron a categorías de menor amenaza. Las especies de cetáceos con áreas de distribución geográficas pequeñas tenían más probabilidades de ser catalogadas como amenazadas que aquellas con áreas de distribución extensas, y aquellas que ocurren en hábitats de agua dulce (100% de las especies) y costeros (60% de las especies) eran las que se encontraban bajo mayor amenaza. La superposición de los mapas de distribución de las especies reveló la existencia de puntos calientes de pequeños cetáceos amenazados en el sudeste asiático y en una zona que abarca el Triángulo de Coral y se extiende por las aguas cercanas a la costa de la Bahía de Bengala, el norte de Australia, Papúa Nueva Guinea y las aguas costeras de China. Urge mejorar la gestión de las pesquerías para limitar la sobrepesca y reducir la captura accesoria con el fin de evitar extinciones o mayores descensos, especialmente en las zonas costeras de Asia, África y Sudamérica.

Guidelines and quantitative standards for improved cetacean taxonomy using full mitochondrial genomes.

In many organisms, especially those of conservation concern, traditional lines of evidence for taxonomic delineation, such as morphological data, are often difficult to obtain. In these cases, genetic data are often the only source of information available for taxonomic studies. In particular, population surveys of mitochondrial genomes offer increased resolution and precision in support of taxonomic decisions relative to conventional use of the control region or other gene fragments of the mitochondrial genome. To improve quantitative guidelines for taxonomic decisions in cetaceans, we build on a previous effort targeting the control region and evaluate, for whole mitogenome sequences, a suite of divergence and diagnosability estimates for pairs of recognized cetacean populations, subspecies, and species. From this overview, we recommend new guidelines based on complete mitogenomes, combined with other types of evidence for isolation and divergence, which will improve resolution for taxonomic decisions, especially in the face of small sample sizes or low levels of genetic diversity. We further use simulated data to assist interpretations of divergence in the context of varying forms of historical demography, culture, and ecology.

Qualitative Evaluation of a Program to Integrate Hepatitis C Care Into HIV Care Inclusive of Task Shifting to Nonspecialist Providers.

The treatment and cure of hepatitis C (HCV) in people with HIV is particularly important as progression of their liver disease is quicker compared with those who have HCV monoinfection. Innovative approaches are needed to maximize access to curative HCV treatment. Integration of HCV care into HIV primary care with education and support of nonspecialist providers via telementoring offers a solution to specialist workforce shortages. Using focus group qualitative methodology, health care workers' perspectives regarding this approach, particularly with the Extension for Community Healthcare Outcomes (ECHO) telementoring model, were obtained and are described. Successful integration of HCV care into HIV primary care has demonstrated benefits to patients, including allowing them to remain in their medical home for care. Factors beyond disease that influence their health and wellbeing must also be considered.

Qualitative study to support the content validity of the immune thrombocytopenia (ITP) Life Quality Index (ILQI).

Immune thrombocytopenia (ITP) is an acquired immune-mediated disorder. Bleeding is the primary symptom that presents in varying severities. ITP has a negative impact on health-related quality of life (HRQoL). The ITP Life Quality Index (ILQI) was developed as a 10-item patient-reported outcome measure to assess impact on HRQoL in ITP. The objective of the present study was to confirm the content validity of the ILQI with a qualitative interview study in the UK involving 15 adult participants with ITP. Combined concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted to explore the symptoms and impacts associated with ITP and confirm content validity of the draft ILQI. The CE phase elicited 14 ITP symptom concepts, including: bruising (all 15 patients, 100%), fatigue (14, 93·3%) and bleeding gums/blood blisters (13, 86·7%). Impacts included decreased ability to participate in sport (all 15 patients, 100%) and anxiety (12, 80%). The CD phase resulted in an adjustment to the ILQI recall period from 1 week to 'the past month'. Updates were made to improve relevance and response options. The qualitative interviews support the content validity of the ILQI and confirm that the concepts assessed are relevant and consistently understood and interpreted by adult patients with ITP.

Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury.

OBJECTIVE: To evaluate the impact of prophylactic indomethacin on early death (<10 days after birth) or severe neurologic injury and on early death or spontaneous intestinal perforation by completed weeks of gestational age in neonates born <29 weeks of gestation. STUDY DESIGN: This was a multicenter, retrospective cohort study of neonates (n = 12 515) born at 236/7 weeks of gestational age, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurologic injury and early death or spontaneous intestinal perforation. RESULTS: Of 12 515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower gestational age and birth weight and had greater severity of illness (Score of Neonatal Acute Physiology with Perinatal Extension) on admission compared with nonrecipients. After we adjusted for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurologic injury and early death or spontaneous intestinal perforation in neonates born at 23-24 weeks of gestational age. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26-28 weeks of gestational age. CONCLUSIONS: Prophylactic indomethacin use was associated with benefit in neonates born at 23-24 weeks of gestational age, but with harm at 26-28 weeks of gestational age. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23-25 weeks of gestational age.

Population structure in a continuously distributed coastal marine species, the harbor porpoise, based on microhaplotypes derived from poor-quality samples.

Harbor porpoise in the North Pacific are found in coastal waters from southern California to Japan, but population structure is poorly known outside of a few local areas. We used multiplexed amplicon sequencing of 292 loci and genotyped clusters of single nucleotide polymoirphisms as microhaplotypes (N = 271 samples) in addition to mitochondrial (mtDNA) sequence data (N = 413 samples) to examine the genetic structure from samples collected along the Pacific coast and inland waterways from California to southern British Columbia. We confirmed an overall pattern of strong isolation-by-distance, suggesting that individual dispersal is restricted. We also found evidence of regions where genetic differences are larger than expected based on geographical distance alone, implying current or historical barriers to gene flow. In particular, the southernmost population in California is genetically distinct (FST  = 0.02 [microhaplotypes]; 0.31 [mtDNA]), with both reduced genetic variability and high frequency of an otherwise rare mtDNA haplotype. At the northern end of our study range, we found significant genetic differentiation of samples from the Strait of Georgia, previously identified as a potential biogeographical boundary or secondary contact zone between harbor porpoise populations. Association of microhaplotypes with remotely sensed environmental variables indicated potential local adaptation, especially at the southern end of the species' range. These results inform conservation and management for this nearshore species, illustrate the value of genomic methods for detecting patterns of genetic structure within a continuously distributed marine species, and highlight the power of microhaplotype genotyping for detecting genetic structure in harbor porpoises despite reliance on poor-quality samples.

Implementing a Skin-to-Skin Care and Parent Touch Initiative in a Tertiary Cardiac and Surgical Neonatal Intensive Care Unit.

BACKGROUND: Skin-to-skin care (SSC) has been integrated as an essential component of developmental care for preterm infants. Despite documented benefits, SSC is not routinely practiced in the cardiac and surgical neonatal intensive care unit, with a predominantly term population, due to staff apprehension, patient factors and acuity, and environmental constraints. PURPOSE: The purpose of this quality improvement project was to increase SSC, parental holds, and parent touch events for infants in our cardiac and surgical neonatal intensive care unit. When traditional SSC was not possible, alternative holds and alternative parent touch (APT) methods were encouraged. METHODS: Quality improvement and qualitative descriptive methodology were utilized to assess baseline, develop education and practice changes, and evaluate the use of SSC, holds, and APT methods at 12 and 18 months postintervention. Implementation included educational tools and resource development, simulations, peer champions, in-class teaching, and team huddles. Decisions around the type of hold and parent touch were fluid and reflected complex infant, family, staff, and physical space needs. FINDINGS: Given its initial scarcity, there was an increased frequency of SSC and variety of holds or APT events. Staff survey results indicated support for the practice and outlined persistent barriers. IMPLICATIONS FOR PRACTICE: Skin-to-skin care, holds, and APT practices are feasible and safe for term and preterm infants receiving highly instrumented and complex cardiac and surgical care. IMPLICATIONS FOR RESEARCH: Future research regarding the intervention's impact on neurodevelopmental outcomes of infants and on parent resilience in the surgical and cardiac neonatal intensive care unit is warranted.

Lack of virologic suppression is associated with lower HIV-related disclosure stigma in people living with HIV.

Stigma remains a leading barrier to HIV care. To determine the influence of disclosure stigma (DS), fear of disclosing one's serostatus, on virologic suppression, a cross-sectional study was performed at the largest publicly-funded HIV clinic in South Texas. A survey was administered to participants who were: ≥18 years old, living with HIV, and receiving antiretroviral therapy. Surveys included demographics, adherence questionnaire, and a validated HIV-stigma scale with DS as the sum of 10 items ranked 0-3, with score of 30 indicating highest stigma. The primary outcome was lack of virologic suppression (LOVS): most recent HIV-1 RNA > 20 copies/ml. A bivariate analyses examined predictors of DS, dichotomized at the median. Depression score, perceived stress, and lack of friend/family support were associated with DS. Logistic regression models examined the relationship between DS, as a continuous variable, and LOVS. For 275 participants (69% Hispanic), median DS score was 18.5. DS was significantly inversely associated with LOVS (aOR 0.94 per 1 scale point; CI 0.89, 0.99) after adjustment for age, gender/sexual orientation, race/ethnicity, and drug use. The unanticipated inverse association between DS and LOVS highlights the complexity of this relationship. However, the balance of data in this cohort demonstrate an overall negative impact of DS.

Low Adherence to Post Emergency Department Follow-Up Among Hypertensive Patients With Medical Insurance.

BACKGROUND: Improvement in hypertension control in the insured, adult population could improve morbidity and mortality associated with hypertension in the United States. The emergency department (ED) is a potential site of intervention, where individuals are diagnosed with asymptomatic hypertension and referred to primary care. OBJECTIVE: To inform intervention strategies, we identified risk factors of nonadherence to primary care follow-up among individuals aged 18-60 years with a primary discharge diagnosis of asymptomatic hypertension in the ED. METHODS: Data were obtained from a commercial claims database for January 2012-September 2015. A total of 84,929 individuals were included. Rate of nonadherence to primary care follow-up was determined for individuals billed for a primary discharge diagnosis of essential hypertension. Multivariate logistic regression was used to calculate adjusted odds ratios. The relationships between demographic and clinical variables with nonadherence to follow-up were assessed. RESULTS: Two-thirds of the study population did not adhere to follow-up within 30 days of ED discharge. Risk factors for nonadherence included no history of recent visit with primary care (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.81-1.93) and multiple prior ED visits (OR 1.65; 95% CI 1.57-1.73). Protective characteristics included history of filling antihypertensive prescriptions in the last year (OR 0.42; 95% CI 0.40-0.43); or history of filling a 30-day antihypertensive prescription on day of diagnosis (OR 0.83; 95% CI 0.80-0.87). CONCLUSIONS: Individuals without a recent primary care visit or who visit the ED frequently are at higher risk of nonadherence to follow-up for hypertension, despite medical insurance. Insurance status may not overcome individual level barriers to follow-up.

Patterns of emergency department use in rural and metropolitan New South Wales from 2012 to 2018.

OBJECTIVE: To explore the patterns of and investigate the factors associated with rises in emergency department presentations in rural and metropolitan New South Wales from 2012 to 2018. DESIGN: A retrospective descriptive study of de-identified data from the New South Wales Emergency Department Data Collection. SETTING: New South Wales, Australia. PARTICIPANTS: All individuals presenting to 99 New South Wales emergency departments, which continuously reported to the Emergency Department Data Collection between 2012 and 2018. A total of 2 166 449 presentations recorded throughout New South Wales in 2012 (rural 786 278; metropolitan 1 380 171) and 2 477 192 in 2018 (rural 861 761; metropolitan 1 615 431). MAIN OUTCOME MEASURES: Total emergency department presentations, plus Poisson regression modelled annual changes in emergency department presentations over the period 2012-2018. RESULTS: Growth in emergency department presentations outpaced population growth in both rural and metropolitan New South Wales between 2012 and 2018. The patterns of age-standardised rates of presentations were broadly similar between rural and metropolitan areas, with highest rates observed in the youngest (0-4 years) and oldest (85+ years) cohorts. The rural sample also displayed a distinct third peak in ages 15-39 years, and rates were higher across all age groups. Rural New South Wales displayed disproportionately higher emergency department presentations in the two most deprived socio-economic status quintiles. While rural New South Wales displayed significant reductions in triage category 5 (non-urgent cases) over time, the relative proportion remained approximately double that of metropolitan sites. CONCLUSIONS: There are differences between rural and metropolitan emergency department presentations relating to demographic factors, triage levels, acuity and admissions. Detailed local investigations are required to determine specific contextual issues that impact on emergency department demand.

Oceanographic barriers, divergence, and admixture: Phylogeography and taxonomy of two putative subspecies of short-finned pilot whale.

Genomic phylogeography plays an important role in describing evolutionary processes and their geographic, ecological, or cultural drivers. These drivers are often poorly understood in marine environments, which have fewer obvious barriers to mixing than terrestrial environments. Taxonomic uncertainty of some taxa (e.g., cetaceans), due to the difficulty in obtaining morphological data, can hamper our understanding of these processes. One such taxon, the short-finned pilot whale, is recognized as a single global species but includes at least two distinct morphological forms described from stranding and drive hunting in Japan, the "Naisa" and "Shiho" forms. Using samples (n = 735) collected throughout their global range, we examine phylogeographic patterns of divergence by comparing mitogenomes and nuclear SNP loci. Our results suggest three types within the species: an Atlantic Ocean type, a western/central Pacific and Indian Ocean (Naisa) type, and an eastern Pacific Ocean and northern Japan (Shiho) type. mtDNA control region differentiation indicates these three types form two subspecies, separated by the East Pacific Barrier: Shiho short-finned pilot whale, in the eastern Pacific Ocean and northern Japan, and Naisa short-finned pilot whale, throughout the remainder of the species' distribution. Our data further indicate two diverging populations within the Naisa subspecies, in the Atlantic Ocean and western/central Pacific and Indian Oceans, separated by the Benguela Barrier off South Africa. This study reveals a process of divergence and speciation within a globally-distributed, mobile marine predator, and indicates the importance of the East Pacific Barrier to this evolutionary process.

Chromatin remodeling complex NURF regulates thymocyte maturation.

The maturation of T cells requires signaling from both cytokine and T-cell receptors to gene targets in chromatin, but how chromatin architecture influences this process is largely unknown. Here we show that thymocyte maturation post-positive selection is dependent on the nucleosome remodeling factor (NURF). Depletion of Bptf (bromodomain PHD finger transcription factor), the largest NURF subunit, in conditional mouse mutants results in developmental arrest beyond the CD4(+) CD8(int) stage without affecting cellular proliferation, cellular apoptosis, or coreceptor gene expression. In the Bptf mutant, specific subsets of genes important for thymocyte development show aberrant expression. We also observed defects in DNase I-hypersensitive chromatin structures at Egr1, a prototypical Bptf-dependent gene that is required for efficient thymocyte development. Moreover, chromatin binding of the sequence-specific factor Srf (serum response factor) to Egr1 regulatory sites is dependent on Bptf function. Physical interactions between NURF and Srf suggest a model in which Srf recruits NURF to facilitate transcription factor binding at Bptf-dependent genes. These findings provide evidence for causal connections between NURF, transcription factor occupancy, and gene regulation during thymocyte development.

Prescription Opioid Use is Associated with Virologic Failure in People Living with HIV.

Prescription opioid misuse is a rising epidemic in the U.S., and people living with HIV are at increased risk. We assessed the association between prescription opioid use and virologic failure in HIV+ patients in the South Texas HIV Cohort. We found prescription opioid use was significantly associated with virologic failure, after adjustment for age, race, gender, insurance status, years living with HIV, reported HIV risk factor, chronic hepatitis C virus infection, current substance abuse, and care engagement. These findings suggest that opioid analgesic use may have negative consequences beyond misuse in people living with HIV.

The rostral medulla of bullfrog tadpoles contains critical lung rhythmogenic and chemosensitive regions across metamorphosis.

The development of amphibian breathing provides insight into vertebrate respiratory control mechanisms. Neural oscillators in the rostral and caudal medulla drive ventilation in amphibians, and previous reports describe ventilatory oscillators and CO2 sensitive regions arise during different stages of amphibian metamorphosis. However, inconsistent findings have been enigmatic, and make comparisons to potential mammalian counterparts challenging. In the current study we assessed amphibian central CO2 responsiveness and respiratory rhythm generation during two different developmental stages. Whole-nerve recordings of respiratory burst activity in cranial and spinal nerves were made from intact or transected brainstems isolated from tadpoles during early or late stages of metamorphosis. Brainstems were transected at the level of the trigeminal nerve, removing rostral structures including the nucleus isthmi, midbrain, and locus coeruleus, or transected at the level of the glossopharyngeal nerve, removing the putative buccal oscillator and caudal medulla. Removal of caudal structures stimulated the frequency of lung ventilatory bursts and revealed a hypercapnic response in normally unresponsive preparations derived from early stage tadpoles. In preparations derived from late stage tadpoles, removal of rostral or caudal structures reduced lung burst frequency, while CO2 responsiveness was retained. Our results illustrate that structures within the rostral medulla are capable of sensing CO2 throughout metamorphic development. Similarly, the region controlling lung ventilation appears to be contained in the rostral medulla throughout metamorphosis. This work offers insight into the consistency of rhythmic respiratory and chemosensitive capacities during metamorphosis.

Antipsychotic Drug Dispensations in Older Adults, Including Continuation After a Fall-Related Hospitalization: Identifying Adherence to Screening Tool of Older Persons' Potentially Inappropriate Prescriptions Criteria Using the Nova Scotia Seniors' Pharmacare Program and Canadian Institute for Health's Discharge Databases.

PURPOSE: Despite well-established concerns regarding adverse drug effects, antipsychotics are frequently prescribed for older adults. Our first objective was to identify trends in antipsychotic dispensations to older Nova Scotians. STOPP (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions) criteria identify antipsychotic use in those with a history of falls as potentially inappropriate. Our second objective was to identify trends, predictors, and adherence with this STOPP criteria by identifying continued antipsychotic dispensations following a fall-related hospitalization. METHODS: A descriptive cross-sectional cohort study of Nova Scotia Seniors' Pharmacare Program (NSSPP) beneficiaries ≥ 66 years with at least one antipsychotic dispensation annually from April 1, 2009 to March 31, 2014 was completed. As well, unique beneficiaries with at least one antipsychotic dispensation in the four-year period between April 1, 2009 and March 31, 2013 were linked to fall-related hospitalizations recorded in the Canadian Institute for Health Information Discharge Abstract Database. The relationship of age, sex, fiscal year, days supply and length-of-stay were studied to identify predictors of continued antipsychotic dispensation post-discharge. Descriptive statistics and multivariate logistic analysis were performed. Odds ratios for the association of risk factors and adherence to STOPP criteria were calculated. FINDINGS: We identified that in each year observed, there were 6% of eligible NSSPP beneficiaries that received at least one antipsychotic dispensation. Approximately 70% of antipsychotic dispensations were for second generation agents, primarily quetiapine and risperidone. Of the unique beneficiaries with at least one antipsychotic dispensation in the four-year period between April 1, 2009 and March 31, 2013 who survived a fall-related hospitalization over 75% were dispensed an antipsychotic in the 100 days following hospital discharge. Logistic regression showed no statistically significant association between potentially inappropriate therapy and potential predictors in multivariate analysis. IMPLICATIONS: In each year from 2009 to 2014, 6% of Nova Scotia Seniors' Pharmacare beneficiaries were dispensed at least one antipsychotic prescription. Over 75% of the older adults who received an antipsychotic dispensation in the 100 days prior to a fall-related hospitalization, continued the drug class after discharge. This demonstrates that despite the recommendations of quality indicators such as the STOPP criteria, antipsychotics are continued in individuals at a high risk of falling. Future investigations are needed to inform health team, system, and policy interventions to improve concordance with this antipsychotic specific STOPP criterion when appropriate.

Cell death regulates muscle fiber number.

Cell death can have both cell autonomous and non-autonomous roles in normal development. Previous studies have shown that the central cell death regulators grim and reaper are required for the developmentally important elimination of stem cells and neurons in the developing central nervous system (CNS). Here we show that cell death in the nervous system is also required for normal muscle development. In the absence of grim and reaper, there is an increase in the number of fibers in the ventral abdominal muscles in the Drosophila adult. This phenotype can be partially recapitulated by inhibition of cell death specifically in the CNS, indicating a non-autonomous role for neuronal death in limiting muscle fiber number. We also show that FGFs produced in the cell death defective nervous system are required for the increase in muscle fiber number. Cell death in the muscle lineage during pupal stages also plays a role in specifying fiber number. Our work suggests that FGFs from the CNS act as a survival signal for muscle founder cells. Thus, proper muscle fiber specification requires cell death in both the nervous system and in the developing muscle itself.

Passive acoustic monitoring of the decline of Mexico's critically endangered vaquita.

The vaquita (Phocoena sinus) is the world's most endangered marine mammal with approximately 245 individuals remaining in 2008. This species of porpoise is endemic to the northern Gulf of California, Mexico, and historically the population has declined because of unsustainable bycatch in gillnets. An illegal gillnet fishery for an endangered fish, the totoaba (Totoaba macdonaldi), has recently resurged throughout the vaquita's range. The secretive but lucrative wildlife trade with China for totoaba swim bladders has probably increased vaquita bycatch mortality by an unknown amount. Precise population monitoring by visual surveys is difficult because vaquitas are inherently hard to see and have now become so rare that sighting rates are very low. However, their echolocation clicks can be identified readily on specialized acoustic detectors. Acoustic detections on an array of 46 moored detectors indicated vaquita acoustic activity declined by 80% between 2011 and 2015 in the central part of the species' range. Statistical models estimated an annual rate of decline of 34% (95% Bayesian credible interval -48% to -21%). Based on results from 2011 to 2014, the government of Mexico enacted and is enforcing an emergency 2-year ban on gillnets throughout the species' range to prevent extinction, at a cost of US$74 million to compensate fishers. Developing precise acoustic monitoring methods proved critical to exposing the severity of vaquitas' decline and emphasizes the need for continual monitoring to effectively manage critically endangered species.