Genome sequence of the tsetse fly (Glossina morsitans):Vector of African trypanosomiasis

Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes of adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between tsetse and other disease vectors include obligate microbial symbioses, viviparous reproduction, and lactation. Here, we describe the sequence and annotation of the 366-megabase Glossina morsitans morsitans genome. Analysis of the genome and the 12,308 predicted protein-encoding genes led to multiple discoveries, including chromosomal integrations of bacterial (Wolbachia) genome sequences, a family of lactation-specific proteins, reduced complement of host pathogen recognition proteins, and reduced olfaction/chemosensory associated genes. These genome data provide a foundation for research into trypanosomiasis prevention and yield important insights with broad implications for multiple aspects of tsetse biology.IS

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

The woman in the muslin mask Gendered representations of veiling and the search for identity in postcolonial literature

Available from British Library Document Supply Centre- DSC:DXN056786 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

High preponderance of BRAF V600E mutation in papillary thyroid carcinoma (PTC) among Filipinos: A clinicopathologic study

Purpose BRAF mutation in papillary thyroid carcinoma (PTC) is associated with an aggressive phenotype, with varying incidence. We evaluated the prevalence of BRAF mutations in PTC among Filipino patients and their correlation with clinicopathologic characteristics. Patients and Methods Clinicopathologic data were retrieved from 64 sequential patients who un- derwent thyroidectomy from June 2016 to December 2016. BRAF mutation testing was performed using Sanger sequencing. Results Eighteen (28%) of 64 patients were diagnosed with PTC; 12 (70.59%) of 17 harbored a BRAF V600E mutation (no amplification in one patient). Demographics of patients with PTC were as follows: 13 women and five men, with median age of 46 years (range, 25 to 74 years). Four- teen patients had conventional subtype PTC; two, follicular variant; one, oncocytic variant; and one, tall-cell features. Tumor size ranged from 0.8 to 7.0 cm (median, 2.4 cm); extrathyroidal extension was present in seven (38.9%) of 18 patients, multifocality in six (33.33%) of eight, and lymph node involvement in eight (44.4%) of 18. Significant association between presence of a BRAF mutation and presence of extrathyroidal extension or lymph node involvement was not determined due to the limited sample size. Conclusion The high preponderance of BRAF mutation (70.59%) suggests some correlation with the previously reported lower 5-year survival among Filipinos. This warrants further investigation in a larger-cohort prospective study

Genomics facilitates evaluation and monitoring of McCloud River Redband Trout (Oncorhynchus mykiss stonei)

AbstractThe McCloud River Redband Trout (MRRT; Oncorhynchus mykiss stonei) is a unique subspecies of rainbow trout that inhabits the isolated Upper McCloud River of Northern California. A major threat to MRRT is introgressive hybridization with non-native rainbow trout from historical stocking and contemporary unauthorized introductions. To help address this concern, we collected RAD-sequencing data on 308 total individuals from MRRT and other California O. mykiss populations and examined population structure using Principal Component and admixture analyses. Our results are consistent with previous studies; we found that populations of MRRT in Sheepheaven, Swamp, Edson, and Moosehead creeks are nonintrogressed. Additionally, we saw no evidence of introgression in Dry Creek, and suggest further investigation to determine if it can be considered a core MRRT conservation population. Sheepheaven Creek was previously thought to be the sole historical lineage of MRRT, but our analysis identified three: Sheepheaven, Edson, and Dry creeks, all of which should be preserved. Finally, we discovered diagnostic and polymorphic SNP markers for monitoring introgression and genetic diversity in MRRT. Collectively, our results provide a valuable resource for the conservation and management of MRRT

Captive-reared Delta Smelt (Hypomesus transpacificus) exhibit high survival in natural conditions using in situ enclosures.

Conservation of endangered fishes commonly includes captive breeding, applied research, and management. Since 1996, a captive breeding program has existed for the federally threatened and California endangered Delta Smelt Hypomesus transpacificus, an osmerid fish endemic to the upper San Francisco Estuary. Although this program serves as a captive refuge population, with experimental releases being initiated to supplement the wild population, it was uncertain how individuals would survive, feed, and maintain condition outside hatchery conditions. We evaluated this and the effects of three enclosure designs (41% open, 63% open, and 63% open with partial outer mesh wrap) on growth, survival, and feeding efficacy of cultured Delta Smelt at two locations (Sacramento River near Rio Vista, CA and in Sacramento River Deepwater Ship Channel) in the wild. Enclosures exposed fish to semi-natural conditions (ambient environmental fluctuations and wild food resources) but prevented escape and predation. After four weeks, survival was high for all enclosure types (94-100%) at both locations. The change in condition and weight was variable between sites, increasing at the first location but decreasing at the second location. Gut content analysis showed that fish consumed wild zooplankton that came into the enclosures. Cumulatively, results show that captive-reared Delta Smelt can survive and forage successfully when housed in enclosures under semi-natural conditions in the wild. When comparing enclosure types, we observed no significant difference in fish weight changes (p = 0.58-0.81 across sites). The success of housing captive-reared Delta Smelt in enclosures in the wild provides preliminary evidence that these fish may be suitable to supplement the wild population in the San Francisco Estuary. Furthermore, these enclosures are a new tool to test the efficacy of habitat management actions or to acclimate fish to wild conditions as a soft release strategy for recently initiated supplementation efforts

Racial and Sex Inequities in the Use of and Outcomes After Left Ventricular Assist Device Implantation Among Medicare Beneficiaries

Background: Racial disparities in access to advanced therapies for heart failure (HF) patients are well documented, although the reasons remain uncertain. We sought to determine the association of race on utilization of ventricular assist device (VAD) and transplant among patients with access to care at VAD centers and if patient preferences impact the effect. Methods: We performed an observational cohort study of ambulatory chronic systolic HF patients with high-risk features and no contraindication to VAD enrolled at 21 VAD centers and followed for 2 years in the REVIVAL study (Registry Evaluation of Vital Information for VADs in Ambulatory Life). We used competing events cause-specific proportional hazard methodology with multiple imputation for missing data. The primary outcomes were (1) VAD/transplant and (2) death. The exposures of interest included race (Black or White), additional demographics, captured social determinants of health, clinician-assessed HF severity, patient-reported quality of life, preference for VAD, and desire for therapies. Results: The study included 377 participants, of whom 100 (26.5%) identified as Black. VAD or transplant was performed in 11 (11%) Black and 62 (22%) White participants, although death occurred in 18 (18%) Black and 36 (13%) White participants. Black race was associated with reduced utilization of VAD and transplant (adjusted hazard ratio, 0.45 [95% CI, 0.23–0.85]) without an increase in death. Preferences for VAD or life-sustaining therapies were similar by race and did not explain racial disparities. Conclusions: Among patients receiving care by advanced HF cardiologists at VAD centers, there is less utilization of VAD and transplant for Black patients even after adjusting for HF severity, quality of life, and social determinants of health, despite similar care preferences. This residual inequity may be a consequence of structural racism and discrimination or provider bias impacting decision-making.NHLBI contract HHSN268201100026C; K12 HL138039-02 to Dr CascinoNCATS grant UL1TR002240an Amplifier Grant Award from the Samuel and Jean Frankel Cardiovascular CenterPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175811/1/cascino_2022_oi_220653_1658260082.24778 (1).pdfDescription of cascino_2022_oi_220653_1658260082.24778 (1).pdf : Main articl

Captive-reared Delta Smelt (Hypomesus transpacificus) exhibit high survival in natural conditions using in situ enclosures.

Conservation of endangered fishes commonly includes captive breeding, applied research, and management. Since 1996, a captive breeding program has existed for the federally threatened and California endangered Delta Smelt Hypomesus transpacificus, an osmerid fish endemic to the upper San Francisco Estuary. Although this program serves as a captive refuge population, with experimental releases being initiated to supplement the wild population, it was uncertain how individuals would survive, feed, and maintain condition outside hatchery conditions. We evaluated this and the effects of three enclosure designs (41% open, 63% open, and 63% open with partial outer mesh wrap) on growth, survival, and feeding efficacy of cultured Delta Smelt at two locations (Sacramento River near Rio Vista, CA and in Sacramento River Deepwater Ship Channel) in the wild. Enclosures exposed fish to semi-natural conditions (ambient environmental fluctuations and wild food resources) but prevented escape and predation. After four weeks, survival was high for all enclosure types (94-100%) at both locations. The change in condition and weight was variable between sites, increasing at the first location but decreasing at the second location. Gut content analysis showed that fish consumed wild zooplankton that came into the enclosures. Cumulatively, results show that captive-reared Delta Smelt can survive and forage successfully when housed in enclosures under semi-natural conditions in the wild. When comparing enclosure types, we observed no significant difference in fish weight changes (p = 0.58-0.81 across sites). The success of housing captive-reared Delta Smelt in enclosures in the wild provides preliminary evidence that these fish may be suitable to supplement the wild population in the San Francisco Estuary. Furthermore, these enclosures are a new tool to test the efficacy of habitat management actions or to acclimate fish to wild conditions as a soft release strategy for recently initiated supplementation efforts

SMPD4 regulates mitotic nuclear envelope dynamics and its loss causes microcephaly and diabetes.

peer reviewedBiallelic loss of function (LoF) variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyzes sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope (NE), and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of LoF SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival. All individuals surviving beyond infancy developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder (NDD) and microcephaly, making diabetes one of the most frequent age-dependent non-cerebral abnormalities. We studied the function of SMPD4 at the cellular and organ levels. Knock-down of SMPD4 in human neural stem cells, causes reduced proliferation rates and prolonged mitosis. Moreover, SMPD4 depletion results in abnormal NE breakdown and reassembly during mitosis and decreased post-mitotic NPC insertion. Fibroblasts from affected individuals show deficient SMPD4-specific neutral sphingomyelinase activity, without changing (sub)cellular lipidome fractions, which suggests a local function of SMPD4 on the NE. In embryonic mouse brain, knockdown of Smpd4 impairs cortical progenitor proliferation and induces premature differentiation by altering the balance between neurogenic and proliferative progenitor cell divisions. We hypothesize that, in individuals with SMPD4-related disease, NE bending, which is needed to insert NPCs in the nuclear envelope, is impaired in the absence of SMPD4, and interferes with cerebral corticogenesis and survival of pancreatic beta cells