Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance ...and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104-4591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences.
ObjectivesTo determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia.DesignA systematic, postmortem prevalence study.SettingA busy, inner-city morgue in Lusaka.ParticipantsWe ...sampled a random subset of all decedents who transited the University Teaching Hospital morgue. We sampled the posterior nasopharynx of decedents using quantitative PCR. Prevalence was weighted to account for age-specific enrolment strategies.InterventionsNot applicable—this was an observational study.Primary outcomesPrevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time.Secondary outcomesShifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates.ResultsFrom 1118 decedents enrolled between January and June 2021, COVID-19 was detected among 32.0% (358/1116). Roughly four COVID-19+ community deaths occurred for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ~10% of COVID-19+ deaths were identified in life. During peak transmission periods, COVID-19 was detected in ~90% of all deaths. We observed three waves of transmission that peaked in July 2020, January 2021 and ~June 2021: the AE.1 lineage and the Beta and Delta variants, respectively. PCR signals were strongest among those whose deaths were deemed ‘probably due to COVID-19’, and weakest among children, with an age-dependent increase in PCR signal intensity.ConclusionsCOVID-19 was common among deceased individuals in Lusaka. Antemortem testing was rarely done, and almost never for community deaths. Suspicion that COVID-19 was the cause of deaths was highest for those with a respiratory syndrome and lowest for individuals <19 years.
Injuries represent a global public health threat and that threat is disproportionally felt especially in low and middle income countries (LMICs) that experience 90% of global mortality from injury. ...Few LMICs have robust datasets describing patient injuries and injury care. Objective: To develop a hospital-based trauma registry in an urban hospital in Lusaka, Zambia to assess patterns of injury, transport methods and duration, injury severity, outcomes and hospital resource utilisation.
From September 2011 to February 2012, all injured patients presenting to the Surgical Emergency Centre at University Teaching Hospital (UTH) were prospectively enrolled in an observational study to describe the epidemiology and the circumstances of injury of patients presenting to UTH, a 1400 bed urban hospital which is the primary trauma centre for Lusaka. Data on injured patients were collected by trained staff 24h/day including: circumstances of trauma, transport method and time, injury type and location, vital signs on arrival, and disposition. Additional data regarding length of stay, HIV testing, operative procedures, use of blood products, and 30-day vital status were recorded for admitted patients.
A total of 3498 patients were enrolled in the trauma registry. Patients were primarily male (71.8%), young (median age 24years), and the majority arrived by private vehicle (51.8%) or public transport (37.1%). The most common reported mechanisms of injury were falls (26.3%), road traffic accidents (25.6%) and assault (20.0%). Hospital resource utilisation data were available for 863 of the 1769 (48.7%) admitted patients. Of these, 661 (76.6%) had X-rays, 468 (57.5%) had a surgical procedure performed, 390 (45.2%) underwent HIV testing, and 50 (5.8%) received blood products. The case fatality rate was 3%.
Limited dataset trauma registries can capture important epidemiologic data that can characterise injury care, identify patterns of injury, and inform hospital-based intervention strategies in Zambia.
Les blessures constituent une menace pour la santé publique mondiale, menace qui se fait ressentir de manière disproportionnée dans les pays à faible et moyen revenu, qui font les frais de 90% de la mortalité mondiale découlant de blessures. Peu de pays à faible et moyen revenu disposent de données fiables décrivant les blessures des patients et la prise en charge des blessures. Objectif: Développer un registre des traumatismes en milieu hospitalier dans un hôpital urbain à Lusaka, en Zambie, afin d’étudier les types des blessures, les modes de transport utilisés et la durée du transport, la gravité des blessures, les résultats et l’utilisation des ressources hospitalières.
De septembre 2011 à février 2012, tous les patients blessés se présentant au service de chirurgie traumatologique de l’hôpital universitaire (CHU) étaient intégrés de manière prospective à une étude observationnelle afin de décrire l’épidémiologie et les circonstances des blessures des patients se présentant au CHU, un hôpital urbain de 1400 lits, principal centre de prise en charge des traumatismes à Lusaka. Les données relatives aux patients blessés ont été recueillies par un personnel formé, 24heures/24. Il s’agissait notamment des informations suivantes: les circonstances du traumatisme, le mode de transport et sa durée, le type de blessure et sa localisation, les signes vitaux à l’arrivée et à la sortie des patients. Des données supplémentaires ont été enregistrées concernant la durée de l’hospitalisation, le dépistage du VIH, les procédures opératoires, l’utilisation de produits sanguins, et l’état de santé à 30 jours pour les patients hospitalisés.
Au total, 3498 patients ont été intégrés au registre des traumatismes. Les patients étaient des hommes pour l’essentiel (71.8%), jeunes (âge médian 24 ans) et la majorité arrivait par véhicule privé (51.8%) ou par les transports publics (37.1%). Les mécanismes de blessure les plus couramment rapportés étaient les chutes (26.3%), les accidents de la route (25.6%) et les agressions (20%). Les données relatives à l’utilisation des ressources hospitalières étaient disponibles pour 863 des 1 769 (48.7%) patients hospitalisés. Parmi eux, 661 (76.6%) avaient passé une radio, 468 (57.5%) avaient été opérés, 390 (45.2%) avaient passé un test de dépistage du VIH et 50 (5.8%) avaient reçu des produits sanguins. Le taux de décès s’élevait à 3%.
Des registres des traumatismes incluant un nombre limité de données peuvent saisir d’importantes données épidémiologiques pouvant permettre de définir les types des blessures et d’informer des stratégies d’intervention hospitalières en Zambie.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and a key driver of childhood mortality. Previous RSV burden of disease estimates used ...hospital-based surveillance data and modelled, rather than directly measured, community deaths. Given this uncertainty, we conducted a 3-year post-mortem prevalence study among young infants at a busy morgue in Lusaka, Zambia—the Zambia Pertussis RSV Infant Mortality Estimation (ZPRIME) study.
Infants were eligible for inclusion if they were aged between 4 days and less than 6 months and were enrolled within 48 h of death. Enrolment occurred mainly at the University Teaching Hospital of the University of Zambia Medical School (Lusaka, Zambia), the largest teaching hospital in Zambia. We extracted demographic and clinical data from medical charts and official death certificates, and we conducted verbal autopsies with the guardian or next of kin. RSV was identified using reverse transcriptase quantitative PCR and stratified by age, time of year, and setting (community vs facility deaths). By combining the PCR prevalence data with syndromic presentation, we estimated the proportion of all infant deaths that were due to RSV.
The ZPRIME study ran from Aug 31, 2017, to Aug 31, 2020, except for from April 1 to May 6, 2020, during which data were not collected due to restrictions on human research at this time (linked to COVID-19). We enrolled 2286 deceased infants, representing 79% of total infant deaths in Lusaka. RSV was detected in 162 (7%) of 2286 deceased infants. RSV was detected in 102 (9%) of 1176 community deaths, compared with 10 (4%) of 236 early facility deaths (<48 h from admission) and 36 (5%) of 737 late facility deaths (≥48 h from admission). RSV deaths were concentrated in infants younger than 3 months (116 72% of 162 infants), and were clustered in the first half of each year and in the poorest and most densely populated Lusaka townships. RSV caused at least 2·8% (95% CI 1·0–4·6) of all infant deaths and 4·7% (1·3–8·1) of community deaths.
RSV was a major seasonal cause of overall infant mortality, particularly among infants younger than 3 months of age. Because most RSV deaths occurred in the community and would have been missed through hospital-based surveillance, the global burden of fatal RSV has probably been underestimated.
Bill & Melinda Gates Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine the impact of basal-like and classical subtypes in advanced pancreatic ductal adenocarcinoma (PDAC) and to explore GATA6 expression as a surrogate biomarker.
Within the COMPASS trial, ...patients proceeding to chemotherapy for advanced PDAC undergo tumor biopsy for RNA-sequencing (RNA-seq). Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received. Correlation of
with the subtypes using gene expression profiling,
hybridization (ISH) was explored.
Between December 2015 and May 2019, 195 patients (95%) had enough tissue for RNA-seq; 39 (20%) were classified as basal-like and 156 (80%) as classical. RECIST response data were available for 157 patients; 29 basal-like and 128 classical where the ORR was 10% versus 33%, respectively (
= 0.02). In patients with basal-like tumors treated with modified FOLFIRINOX (
= 22), the progression rate was 60% compared with 15% in classical PDAC (
= 0.0002). Median OS in the intention-to-treat population (
= 195) was 9.3 months for classical versus 5.9 months for basal-like PDAC (HR, 0.47; 95% confidence interval, 0.32-0.69;
= 0.0001).
expression by RNA-seq highly correlated with the classifier (
< 0.001) and ISH predicted the subtypes with sensitivity of 89% and specificity of 83%. In a multivariate analysis, GATA6 expression was prognostic (
= 0.02). In exploratory analyses, basal-like tumors, could be identified by keratin 5, were more hypoxic and enriched for a T-cell-inflamed gene expression signature.
The basal-like subtype is chemoresistant and can be distinguished from classical PDAC by GATA6 expression.
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Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, ...judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women.
HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18–45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564.
From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22–30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% 95% CI 0·73–1·40); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years 0·06–0·52) and 36 in the TDF-FTC group (1·85 cases per 100 person-years 1·3–2·57; hazard ratio 0·12 0·05–0·31; p<0·0001; risk difference –1·6% –1·0% to –2·3%. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 38·0% of 1519 vs 162 10·7% of 1516) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9–1·7); no congenital birth anomalies were reported.
Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women.
National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Reward and punishment are potent modulators of associative learning in instrumental and classical conditioning. However, the effect of reward and punishment on procedural learning is not known. The ...striatum is known to be an important locus of reward-related neural signals and part of the neural substrate of procedural learning. Here, using an implicit motor learning task, we show that reward leads to enhancement of learning in human subjects, whereas punishment is associated only with improvement in motor performance. Furthermore, these behavioral effects have distinct neural substrates with the learning effect of reward being mediated through the dorsal striatum and the performance effect of punishment through the insula. Our results suggest that reward and punishment engage separate motivational systems with distinctive behavioral effects and neural substrates.
Pancreatic adenocarcinoma presents as a spectrum of a highly aggressive disease in patients. The basis of this disease heterogeneity has proved difficult to resolve due to poor tumor cellularity and ...extensive genomic instability. To address this, a dataset of whole genomes and transcriptomes was generated from purified epithelium of primary and metastatic tumors. Transcriptome analysis demonstrated that molecular subtypes are a product of a gene expression continuum driven by a mixture of intratumoral subpopulations, which was confirmed by single-cell analysis. Integrated whole-genome analysis uncovered that molecular subtypes are linked to specific copy number aberrations in genes such as mutant KRAS and GATA6. By mapping tumor genetic histories, tetraploidization emerged as a key mutational process behind these events. Taken together, these data support the premise that the constellation of genomic aberrations in the tumor gives rise to the molecular subtype, and that disease heterogeneity is due to ongoing genomic instability during progression.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Advances in cosmic microwave background (CMB) science depend on increasing the number of sensitive detectors observing the sky. New instruments deploy large arrays of superconducting ...transition-edge sensor (TES) bolometers tiled densely into ever larger focal planes. High multiplexing factors reduce the thermal loading on the cryogenic receivers and simplify their design. We present the design of focal-plane modules with an order of magnitude higher multiplexing factor than has previously been achieved with TES bolometers. We focus on the novel cold readout component, which employs microwave SQUID multiplexing (
μ
mux). Simons Observatory will use 49 modules containing 70,000 bolometers to make exquisitely sensitive measurements of the CMB. We validate the focal-plane module design, presenting measurements of the readout component with and without a prototype detector array of 1728 polarization-sensitive bolometers coupled to feedhorns. The readout component achieves a 95% yield and a 910 multiplexing factor. The median white noise of each readout channel is 65
pA
/
Hz
. This impacts the projected SO mapping speed by <8%, which is less than is assumed in the sensitivity projections. The results validate the full functionality of the module. We discuss the measured performance in the context of SO science requirements, which are exceeded.
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