Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Quantifying biomass and canopy cover of submerged aquatic vegetation on an offshore island

International audienceThe coverage and biomass of submerged aquatic vegetation (SAV) are vital characteristics of marine resourcemanagement and development. However, using in situ measurements to assess the distributionand biomass of SAV is challenging because SAV distribution varies with biomass, substrate type, anddepth, making it difficult to monitor. Satellite remote sensing is an advanced tool that can tackle thisproblem. In this study, several techniques, such as atmospheric correction, water column correction,and supervised classification, were integrated with Landsat-8 images to map SAV distribution on anoffshore island in Viet Nam, Ly Son island. The substrate-classifying result had high accuracy (OA =92.6%, K = 0.9 ). The coastal, blue, and green bands of Landsat-8 were used to estimate the SAVbiomass using a polynomial regression (RMSE = ±1440.6 g fresh m−2, R2 = 0.71). The results showedthat the total fresh biomass of SAV in Ly Son island is 14551.04 tonnes, with a corresponding areaof 332.1 hectares, equivalent to an average biomass of 4381.5 ± 1440.6 g fresh m−2. The distributionand biomass maps of SAV produced in this study could be used as input to measure the attributes ofSAV biodiversity, contributing more effectively to monitoring marine ecosystems in Viet Nam

Non-annual seasonality of influenza-like illness in a tropical urban setting.

BACKGROUND In temperate and sub-tropical climates, respiratory diseases exhibit seasonal peaks in winter. In the tropics, with no winter, peak timings are irregular. METHODS To obtain a detailed picture of influenza-like illness (ILI) patterns in the tropics, we established an mHealth study in community clinics in Ho Chi Minh City (HCMC). During 2009-2015, clinics reported daily case numbers via SMS, with a subset performing molecular diagnostics for influenza virus. This real-time epidemiology network absorbs 6,000 ILI reports annually, one or two orders of magnitude more than typical surveillance systems. A real-time online ILI indicator was developed to inform clinicians of the daily ILI activity in HCMC. RESULTS From August 2009 to December 2015, 63 clinics were enrolled and 37,676 SMS reports were received, covering approximately 1.8M outpatient visits. Approximately 10.6% of outpatients met the ILI case definition. ILI activity in HCMC exhibited strong non-annual dynamics with a dominant periodicity of 206 days. This was confirmed by time-series decomposition, step-wise regression, and a forecasting exercise showing that median forecasting errors are 30%-40% lower when using a 206-day cycle. In ILI patients from whom naso-pharyngeal swabs were taken, 31.2% were positive for influenza. There was no correlation between the ILI time series and the time series of influenza, influenza A, or influenza B (all p > 0.15). CONCLUSION This suggests, for the first-time, that a non-annual cycle may be an essential driver of respiratory disease dynamics in the tropics. An immunological interference hypothesis is discussed as a potential underlying mechanism. This article is protected by copyright. All rights reserved

Large isolated major aortopulmonary collateral artery causing dilated left ventricle

Isolated major aortopulmonary collateral artery (MAPCA), in the absence of evidence of structural heart disease, is a very rare observation. This anomaly usually appears in preterm newborns. In the majority of babies, isolated MAPCAs cause no symptoms and regress spontaneously after birth and their conservative management is usually sufficient. We report a case of an asymptomatic full-term 5-month-old infant presenting with heart murmur as the only sign during clinical evaluation. Echocardiography revealed a dilated left ventricle, with no pulmonary hypertension. Computed tomography angiogram showed a large MAPCA arising from the descending thoracic aorta and supplying blood to the left lower lobe. The condition was managed successfully by percutaneous obliteration with Amplatzer vascular plugs. Isolated MAPCA is usually a benign anomaly, presenting no clinical finding and requiring no specific treatment. However, in a small minority of infants, this congenital disorder may progress, with detrimental impacts on cardiac structure before clinical symptoms appear. Early intervention may be required to prevent irreversible sequelae

Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated <i>Plasmodium falciparum</i> malaria: a multicentre, open-label, randomised clinical trial.

Background:Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance. Methods: In this multicentre, open-label, randomised trial, we recruited patients with uncomplicated P falciparum malaria at 18 hospitals and health clinics in eight countries. Eligible patients were aged 2-65 years, with acute, uncomplicated P falciparum malaria alone or mixed with non-falciparum species, and a temperature of 37·5°C or higher, or a history of fever in the past 24 h. Patients were randomly assigned (1:1) to one of two treatments using block randomisation, depending on their location: in Thailand, Cambodia, Vietnam, and Myanmar patients were assigned to either dihydroartemisinin-piperaquine or dihydroartemisinin-piperaquine plus mefloquine; at three sites in Cambodia they were assigned to either artesunate-mefloquine or dihydroartemisinin-piperaquine plus mefloquine; and in Laos, Myanmar, Bangladesh, India, and the Democratic Republic of the Congo they were assigned to either artemether-lumefantrine or artemether-lumefantrine plus amodiaquine. All drugs were administered orally and doses varied by drug combination and site. Patients were followed-up weekly for 42 days. The primary endpoint was efficacy, defined by 42-day PCR-corrected adequate clinical and parasitological response. Primary analysis was by intention to treat. A detailed assessment of safety and tolerability of the study drugs was done in all patients randomly assigned to treatment. This study is registered at ClinicalTrials.gov, NCT02453308, and is complete. Findings: Between Aug 7, 2015, and Feb 8, 2018, 1100 patients were given either dihydroartemisinin-piperaquine (183 [17%]), dihydroartemisinin-piperaquine plus mefloquine (269 [25%]), artesunate-mefloquine (73 [7%]), artemether-lumefantrine (289 [26%]), or artemether-lumefantrine plus amodiaquine (286 [26%]). The median age was 23 years (IQR 13 to 34) and 854 (78%) of 1100 patients were male. In Cambodia, Thailand, and Vietnam the 42-day PCR-corrected efficacy after dihydroartemisinin-piperaquine plus mefloquine was 98% (149 of 152; 95% CI 94 to 100) and after dihydroartemisinin-piperaquine was 48% (67 of 141; 95% CI 39 to 56; risk difference 51%, 95% CI 42 to 59; p Interpretation: Dihydroartemisinin-piperaquine plus mefloquine and artemether-lumefantrine plus amodiaquine TACTs are efficacious, well tolerated, and safe treatments of uncomplicated P falciparum malaria, including in areas with artemisinin and ACT partner-drug resistance

Proceedings of the 5th Conference on Language Teaching and Learning

This conference proceedings contains articles on the various research ideas of the academic community and practitioners presented at the 5th Conference on Language Teaching and Learning (LTAL-2023). LTAL2023 was organized by the Ho Chi Minh City University of Food Industry, Vietnam on May 7, 2023. Conference Title: 5th Conference on Language Teaching and LearningConference Acronym: LTAL-2023Conference Date: 7 May 2023Conference Location: VietnamConference Organizers: Ho Chi Minh City University of Food Industry, Vietnam. Related Proceedings:  Proceedings of the 4th Conference on Language Teaching and Learnin