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Abstract Background Malaria elimination in Senegal requires accurate diagnosis of all Plasmodium species. Plasmodium falciparum is the most prevalent species in Senegal, although Plasmodium malariae, Plasmodium ovale, and recently Plasmodium vivax have also been reported. Nonetheless, most malaria control tools, such as Histidine Rich Protein 2 rapid diagnosis test (PfHRP2-RDT,) can only diagnose P. falciparum. Thus, PfHRP2-RDT misses non-falciparum species and P. falciparum infections that fall below the limit of detection. These limitations can be addressed using highly sensitive Next Generation Sequencing (NGS). This study assesses the burden of the four different Plasmodium species in western and eastern regions of Senegal using targeted PCR amplicon sequencing. Methods Three thousand samples from symptomatic and asymptomatic individuals in 2021 from three sites in Senegal (Sessene, Diourbel region; Parcelles Assainies, Kaolack region; Gabou, Tambacounda region) were collected. All samples were tested using PfHRP2-RDT and photoinduced electron transfer polymerase chain reaction (PET-PCR), which detects all Plasmodium species. Targeted sequencing of the nuclear 18S rRNA and the mitochondrial cytochrome B genes was performed on PET-PCR positive samples. Results Malaria prevalence by PfHRP2-RDT showed 9.4% (94/1000) and 0.2% (2/1000) in Diourbel (DBL) and Kaolack (KL), respectively. In Tambacounda (TAM) patients who had malaria symptoms and had a negative PfHRP2-RDT were enrolled. The PET-PCR had a positivity rate of 23.5% (295/1255) overall. The PET-PCR positivity rate was 37.6%, 12.3%, and 22.8% in Diourbel, Kaolack, and Tambacounda, respectively. Successful sequencing of 121/295 positive samples detected P. falciparum (93%), P. vivax (2.6%), P. malariae (4.4%), and P. ovale wallikeri (0.9%). Plasmodium vivax was co-identified with P. falciparum in thirteen samples. Sequencing also detected two PfHRP2-RDT-negative mono-infections of P. vivax in Tambacounda and Kaolack. Conclusion The findings demonstrate the circulation of P. vivax in western and eastern Senegal, highlighting the need for improved malaria control strategies and accurate diagnostic tools to better understand the prevalence of non-falciparum species countrywide.

BackgroundTo investigate the impacts of the COVID-19 pandemic on the health workforce, we aimed to develop a framework that synergizes natural language processing (NLP) techniques and human-generated analysis to reduce, organize, classify, and analyze a vast volume of publicly available news articles to complement scientific literature and support strategic policy dialogue, advocacy, and decision-making. ObjectiveThis study aimed to explore the possibility of systematically scanning intelligence from media that are usually not captured or best gathered through structured academic channels and inform on the impacts of the COVID-19 pandemic on the health workforce, contributing factors to the pervasiveness of the impacts, and policy responses, as depicted in publicly available news articles. Our focus was to investigate the impacts of the COVID-19 pandemic and, concurrently, assess the feasibility of gathering health workforce insights from open sources rapidly. MethodsWe conducted an NLP-assisted media content analysis of open-source news coverage on the COVID-19 pandemic published between January 2020 and June 2022. A data set of 3,299,158 English news articles on the COVID-19 pandemic was extracted from the World Health Organization Epidemic Intelligence through Open Sources (EIOS) system. The data preparation phase included developing rules-based classification, fine-tuning an NLP summarization model, and further data processing. Following relevancy evaluation, a deductive-inductive approach was used for the analysis of the summarizations. This included data extraction, inductive coding, and theme grouping. ResultsAfter processing and classifying the initial data set comprising 3,299,158 news articles and reports, a data set of 5131 articles with 3,007,693 words was devised. The NLP summarization model allowed for a reduction in the length of each article resulting in 496,209 words that facilitated agile analysis performed by humans. Media content analysis yielded results in 3 sections: areas of COVID-19 impacts and their pervasiveness, contributing factors to COVID-19–related impacts, and responses to the impacts. The results suggest that insufficient remuneration and compensation packages have been key disruptors for the health workforce during the COVID-19 pandemic, leading to industrial actions and mental health burdens. Shortages of personal protective equipment and occupational risks have increased infection and death risks, particularly at the pandemic’s onset. Workload and staff shortages became a growing disruption as the pandemic progressed. ConclusionsThis study demonstrates the capacity of artificial intelligence–assisted media content analysis applied to open-source news articles and reports concerning the health workforce. Adequate remuneration packages and personal protective equipment supplies should be prioritized as preventive measures to reduce the initial impact of future pandemics on the health workforce. Interventions aimed at lessening the emotional toll and workload need to be formulated as a part of reactive measures, enhancing the efficiency and maintainability of health delivery during a pandemic.

The aim of the work presented in this paper was development of a thermodynamically consistent constitutive model for orthotopic metals and determination of its parameters based on standard characterisation methods used in the aerospace industry. The model was derived with additive decomposition of the strain tensor and consisted of an elastic part, derived from Helmholtz free energy, Hill’s thermodynamic potential, which controls evolution of plastic deformation, and damage orthotopic potential, which controls evolution of damage in material. Damage effects were incorporated using the continuum damage mechanics approach, with the effective stress and energy equivalence principle. Material characterisation and derivation of model parameters was conducted with standard specimens with a uniform cross-section, although a number of tests with non-uniform cross-sections were also conducted here. The tests were designed to assess the extent of damage in material over a range of plastic deformation values, where displacement was measured locally using digital image correlation. The new model was implemented as a user material subroutine in Abaqus and verified and validated against the experimental results for aerospace-grade aluminium alloy 2024-T3. Verification was conducted in a series of single element tests, designed to separately validate elasticity, plasticity and damage-related parts of the model. Validation at this stage of the development was based on comparison of the numerical results with experimental data obtained in the quasistatic characterisation tests, which illustrated the ability of the modelling approach to predict experimentally observed behaviour. A validated user material subroutine allows for efficient simulation-led design improvements of aluminium components, such as stiffened panels and the other thin-wall structures used in the aerospace industry.

With the emergence of the COVID-19 pandemic, the absence of established evidence-based treatment protocols led healthcare professionals and the public to explore experimental treatments, including high doses of vitamin D supplements. This study aimed to assess changes in serum 25-hydroxyvitamin D levels during the pandemic, employing a retrospective cohort analysis of data from Charleston Area Medical Center (CAMC). The study analyzed serum 25-hydroxyvitamin D levels in a cohort of 35,556 patients treated at CAMC in 2019, a representative pre-pandemic period, to 2021, a representative pandemic period. Our findings revealed a significant increase in mean serum 25-hydroxyvitamin D levels as compared with 2019 (37 ± 21 vs. 31 ± 15 ng/mL, p ≤ 0.001). Additionally, in 2021, there were significantly more patients exhibiting serum levels in the highest quintiles, specifically >100 ng/mL (1.6% vs. 0.2%), 75–100 ng/mL (4.6% vs. 1.2%), and 50–75 ng/mL (16.0% vs. 8.4%), p ≤ 0.001. This upsurge suggests increased intake of vitamin D supplements, potentially fueled by widespread discussions that were taking place largely on the internet regarding the efficacy of vitamin D against COVID-19. Our findings underscore the critical need for evidence-based public health messaging, especially during health crises, to prevent unnecessary health risks and ensure patient safety.

Abstract Development partners and global health initiatives are important actors in financing health systems in many countries. Despite the importance of the health workforce to the attainment of global health targets, the contribution of global health initiatives to health workforce strengthening is unclear. A 2020 milestone in the Global Strategy on Human Resources for Health is that “all bilateral and multilateral agencies have participated in efforts to strengthen health workforce assessments and information exchange in countries.” This milestone exists to encourage strategic investments in the health workforce that are evidence-based and incorporate a health labour market approach as an indication of policy comprehensiveness. To assess progress against this milestone, we reviewed the activities of 23 organizations (11 multilaterals and 12 bilaterals) which provide financial and technical assistance to countries for human resources for health, by mapping grey and peer-reviewed literature published between 2016 and 2021. The Global Strategy states that health workforce assessment involves a “deliberate strategy and accountability mechanisms on how specific programming contributes to health workforce capacity-building efforts” and avoids health labour market distortions. Health workforce investments are widely recognized as essential for the achievement of global health goals, and some partners identify health workforce as a key strategic focus in their policy and strategy documents. However, most do not identify it as a key focus, and few have a published specific policy or strategy to guide health workforce investments. Several partners include optional health workforce indicators in their monitoring and evaluation processes and/or require an impact assessment for issues such as the environment and gender equality. Very few, however, have embedded efforts in their governance mechanisms to strengthen health workforce assessments. On the other hand, most have participated in health workforce information exchange activities, including strengthening information systems and health labour market analyses. Although there is evidence of participation in efforts to strengthen health workforce assessments and (especially) information exchange, the achievement of this milestone of the Global Strategy requires more structured policies for the monitoring and evaluation of health workforce investments to optimize the value of these investments and contribute towards global and national health goals.

In this study, a basic insect detection system consisting of a manual-focus camera, a Jetson Nano—a low-cost, low-power single-board computer, and a trained deep learning model was developed. The model was validated through a live visual feed. Detecting, classifying, and monitoring insect pests in a grain storage or food facility in real time is vital to making insect control decisions. The camera captures the image of the insect and passes it to a Jetson Nano for processing. The Jetson Nano runs a trained deep-learning model to detect the presence and species of insects. With three different lighting situations: white LED light, yellow LED light, and no lighting condition, the detection results are displayed on a monitor. Validating using F1 scores and comparing the accuracy based on light sources, the system was tested with a variety of stored grain insect pests and was able to detect and classify adult cigarette beetles and warehouse beetles with acceptable accuracy. The results demonstrate that the system is an effective and affordable automated solution to insect detection. Such an automated insect detection system can help reduce pest control costs and save producers time and energy while safeguarding the quality of stored products.

Background During the COVID-19 pandemic, and recognising the sacrifice of health and care workers alongside discrimination, violence, poor working conditions and other violations of their rights, health and safety, in 2021 the World Health Assembly requested WHO to develop a global health and care worker compact, building on existing normative documentation, to provide guidance to ‘protect health and care workers and safeguard their rights’.Methods A review of existing international law and other normative documents was conducted. We manually searched five main sets of international instruments: (1) International Labour Organization conventions and recommendations; (2) WHO documents; (3) United Nations (UN) human rights treaties and related documents; (4) UN Security Council and General Assembly resolutions and (5) the Geneva Conventions and Additional Protocols. We included only legal or other normative documents with a global or regional focus directly addressing or relevant to health and care workers or workers overall.Results More than 70 documents met our search criteria. Collectively, they fell into four domains, within which we identified 10 distinct areas: (1) preventing harm, encompassing (A) occupational hazards, (B) violence and harassment and (C) attacks in situations of fragility, conflict and violence; (2) inclusivity, encompassing (A) non-discrimination and equality; (3) providing support, encompassing (A) fair and equitable remuneration, (B) social protection and (C) enabling work environments and (4) safeguarding rights, encompassing (A) freedom of association and collective bargaining and (B) whistle-blower protections and freedom from retaliation.Discussion A robust legal and policy framework exists for supporting health and care workers and safeguarding their rights. Specific human rights, the right to health overall, and other binding and non-binding legal documents provide firm grounding for the compact.However, these existing commitments are not being fully met. Implementing the compact will require more effective governance mechanisms and new policies, in partnership with health and care workers themselves.

Abstract Background Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine. Methods The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform. Discussion Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines. Trial registration NCT05031468 .

Diphtheria is a life-threatening, vaccine-preventable disease caused by toxigenic Corynebacterium bacterial species that continues to cause substantial disease and death worldwide, particularly in vulnerable populations. Further outbreaks of vaccine-preventable diseases are forecast because of health service disruptions caused by the coronavirus disease pandemic. Diphtheria causes a spectrum of clinical disease, ranging from cutaneous forms to severe respiratory infections with systemic complications, including cardiac and neurologic. In this synopsis, we describe a case of oropharyngeal diphtheria in a 7-year-old boy in Vietnam who experienced severe myocarditis complications. We also review the cardiac complications of diphtheria and discuss how noninvasive bedside imaging technologies to monitor myocardial function and hemodynamic parameters can help improve the management of this neglected infectious disease.

Background: Little is known about the prevalence and patterns of methicillin-resistant Staphylococcus aureus (MRSA) carriage among healthcare workers (HCWs) in Intensive Care Unit (ICU) especially in low-middle income countries like Vietnam. Materials and Methods: A prospective cohort study was conducted on HCWs working at the Adult ICU of the Hospital for Tropical Diseases (HTD), which is among the leading tertiary referral hospitals for infectious disease in Vietnam between 28th October and 20th December 2019. Hand and nasal swabs were collected weekly in eight consecutive weeks for MRSA screening in 55 HCWs. Risk factors for MRSA carriage were obtained using a questionnaire. Results: One third (29.1%, 16/55) of HCWs carried MRSA in their noses or hands. MRSA intermittent hand carriage was documented in 3.6% (2/55) of HCWs. Among 53 HCWs undertaking nasal swabs, 24.5% were MRSA persistent and 5.6% were intermittent carriers. MRSA carriage rate was highest among nursing aids (50%, 4/8). More HCWs with underlying diseases were found to be MRSA carriers compared with those without comorbidities (31.8%, 7/22 vs 27.3%, 9/33). Conclusion: MRSA carriage among HCWs is not rare. The findings highlight an urgent need to review and update the local infection prevention and control measures to prevent MRSA transmission from HCWs to patients.

Abstract Multispectral photoacoustic tomography enables the resolution of spectral components of a tissue or sample at high spatiotemporal resolution. With the availability of commercial instruments, the acquisition of data using this modality has become consistent and standardized. However, the analysis of such data is often hampered by opaque processing algorithms, which are challenging to verify and validate from a user perspective. Furthermore, such tools are inflexible, often locking users into a restricted set of processing motifs, which may not be able to accommodate the demands of diverse experiments. To address these needs, we have developed a Reconstruction, Analysis, and Filtering Toolbox to support the analysis of photoacoustic imaging data. The toolbox includes several algorithms to improve the overall quantification of photoacoustic imaging, including non-negative constraints and multispectral filters. We demonstrate various use cases, including dynamic imaging challenges and quantification of drug effect, and describe the ability of the toolbox to be parallelized on a high performance computing cluster.

Abstract Background Tetanus remains common in many low- and middle-income countries, but as critical care services improve, mortality from tetanus is improving. Nevertheless, patients develop severe syndromes associated with autonomic nervous system disturbance (ANSD) and the requirement for mechanical ventilation (MV). Understanding factors associated with worse outcome in such settings is important to direct interventions. In this study, we investigate risk factors for disease severity and long-term physical outcome in adults with tetanus admitted to a Vietnamese intensive care unit. Methods Clinical and demographic variables were collected prospectively from 180 adults with tetanus. Physical function component scores (PCS), calculated from Short Form Health Survey (SF-36), were assessed in 79 patients at hospital discharge, 3 and 6 months post discharge. Results Age, temperature, heart rate, lower peripheral oxygen saturation (SpO2) and shorter time from first symptom to admission were associated with MV (OR 1.03 [ 95% confidence interval (CI) 1.00, 1.05], p = 0.04; OR 2.10 [95% CI 1.03, 4.60], p = 0.04; OR 1.04 [ 95% CI 1.01, 1.07], p = 0.02); OR 0.80 [95% CI 0.66, 0.94], p = 0.02 and OR 0.65 [95% CI 0.52, 0.79, p

Objectives The implementation of COVID-19 vaccination globally poses unprecedented stress to health systems particularly for countries with persisting health workforce shortages prior the pandemic. The present paper estimates the workforce requirement to reach 70% COVID-19 vaccination coverage in all countries by mid-2022 using service target–based estimation.Methods Health workforce data from National Health Workforce Accounts and vaccination coverage reported to WHO as of January 2022 were used. Workload parameters were used to estimate the number of health workers needed with a service target–based approach, the gap and the scale-up required partially accounting for countries’ challenges, as well as the associated costs in human resources.Results As of 1 January 2022, only 34 countries achieved 70% COVID-19 vaccination coverage and 61 countries covered less than a quarter of their population. This analysis showed that 1 831 000 health workers working full time would be needed to reach a global coverage of 70% COVID-19 vaccination by mid-2022. To avoid severe disruptions to health system, 744 000 additional health workers should be added to domestic resources mostly (77%) in low-income countries. In a sensitivity analysis, allowing for vaccination over 12 months instead of 6 months would decrease the scale-up to 476 000 health workers. The costing for the employment of these 744 000 additional health workers is estimated to be US$2.5 billion. In addition to such a massive scale-up, it is estimated that 29 countries would have needed to redeploy more than 20% of their domestic workforce, placing them at serious risk of not achieving the mid-year target.Conclusion Reaching 70% global coverage with COVID-19 vaccination by mid-2022 requires extraordinary efforts not before witnessed in the history of immunisation programmes. COVID-19 vaccination programmes should receive rapid and sustainable investment in health workforce.

Abstract Despite the established roles of the epigenetic factor UHRF1 in oncogenesis, no UHRF1-targeting therapeutics have been reported to date. In this study, we use fragment-based ligand discovery to identify novel scaffolds for targeting the isolated UHRF1 tandem Tudor domain (TTD), which recognizes the heterochromatin-associated histone mark H3K9me3 and supports intramolecular contacts with other regions of UHRF1. Using both binding-based and function-based screens of a ~ 2300-fragment library in parallel, we identified 2,4-lutidine as a hit for follow-up NMR and X-ray crystallography studies. Unlike previous reported ligands, 2,4-lutidine binds to two binding pockets that are in close proximity on TTD and so has the potential to be evolved into more potent inhibitors using a fragment-linking strategy. Our study provides a useful starting point for developing potent chemical probes against UHRF1.

In the Mekong Delta region of Vietnam, small-scale chicken farming is common. However, high levels of disease or mortality in such flocks impair economic development and challenge the livelihoods of many rural households. We investigated 61 diseased small-scale flocks (122 chickens) for evidence of infection with 5 bacteria, 4 viruses, and helminths. Serological profiles (ELISA) were also determined against 6 of these pathogens. The aims of this study were the following: (1) to investigate the prevalence of different pathogens and to compare the probability of detection of bacterial pathogens using PCR and culture; (2) to investigate the relationship between detection of organisms in birds' tissues and the observed morbidity and mortality, as well as their antibody profile; and (3) to characterize risk factors for infection with specific viral or bacterial pathogens. We used PCR to test for viral (viruses causing infectious bronchitis [IB], highly pathogenic avian influenza [HPAI], Newcastle disease, and infectious bursal disease [IBD]) and bacterial pathogens (Mycoplasma gallisepticum, Pasteurella multocida, Avibacterium paragallinarum, and Ornithobacterium rhinotracheale [ORT]). The latter two were also investigated in respiratory tissues by conventional culture. Colisepticemic Escherichia coli was investigated by liver or spleen culture. In 49 of 61 (80.3%) flocks, at least one bacterial or viral pathogen was detected, and in 29 (47.5%) flocks, more than one pathogen was detected. A. paragallinarum was detected in 62.3% flocks, followed by M. gallisepticum (26.2%), viruses causing IBD (24.6%) and IB (21.3%), septicemic E. coli (14.8%), ORT (13.1%), and HPAI viruses (4.9%). Of all flocks, 67.2% flocks were colonized by helminths. Mortality was highest among flocks infected with HPAI (100%, interquartile range [IQR]: 81.6–100%) and lowest with flocks infected with ORT (5.3%, IQR: 1.1–9.0%). The results indicated slight agreement (kappa ≤ 0.167) between detection by PCR and culture for both A. paragallinarum and ORT, as well as between the presence of cestodes and ORT infection (kappa = 0.317). Control of A. paragallinarum, viruses causing HPAI, IBD, and IB, M. gallisepticum, and gastrointestinal helminths should be a priority in small-scale flocks.

Abstract The ambition of universal health coverage entails estimation of the number, type and distribution of health workers required to meet the population need for health services. The demography of the population, including anticipated or estimated changes, is a factor in determining the ‘universal’ needs for health and well-being. Demography is concerned with the size, breakdown, age and gender structure and dynamics of a population. The same science, and its robust methodologies, is equally applicable to the demography of the health workforce itself. For example, a large percentage of the workforce close to retirement will impact availability, a geographically mobile workforce has implications for health coverage, and gender distribution in occupations may have implications for workforce acceptability and equity of opportunity. In a world with an overall shortage of health workers, and the expectation of increasing need as a result of both population growth in the global south and population ageing in the global north, studying and understanding demographic characteristics of the workforce can help with future planning. This paper discusses the dimensions of health worker demography and considers how demographic tools and techniques can be applied to the analysis of the health labour market. A conceptual framework is introduced as a step towards the application of demographic principles and techniques to health workforce analysis and planning exercises as countries work towards universal health coverage, the reduction of inequities and national development targets. Some illustrative data from Nepal and Finland are shown to illustrate the potential of this framework as a simple and effective contribution to health workforce planning.

Chronic food insecurity remains a challenge globally, exacerbated by climate change-driven shocks such as droughts and floods. Forecasting food insecurity levels and targeting vulnerable households is apriority for humanitarian programming to ensure timely delivery of assistance. In this study, we propose to harness a machine learning approach trained on high-frequency household survey data to infer the predictors of food insecurity and forecast household level outcomes in near real-time. Our empirical analyses leverage the Measurement Indicators for Resilience Analysis (MIRA) data collection protocol implemented by Catholic Relief Services (CRS) in southern Malawi, a series of sentinel sites collecting household data monthly. When focusing on predictors of community-level vulnerability, we show that a random forest model outperforms other algorithms and that location and self-reported welfare are the best predictors of food insecurity. We also show performance results across several neural networks and classical models for various data modeling scenarios to forecast food security. We pose that problem as binary classification via dichotomization of the food security score based on two different thresholds, which results in two different positive class to negative class ratios. Our best performing model has an F1 of 81% and an accuracy of 83% in predicting food security outcomes when the outcome is dichotomized based on threshold 16 and predictor features consist of historical food security score along with 20 variables selected by artificial intelligence explainability frameworks. These results showcase the value of combining high-frequency sentinel site data with machine learning algorithms to predict future food insecurity outcomes.

Abstract Objectives BNT‐162b2, mRNA‐1273, and Ad26.COV2.S vaccines data regarding adverse events (AEs) are scarce. In this report, we aimed to describe fatal and non‐fatal possible AEs after COVID‐19 vaccine administration. Methods An observational multicenter study investigating the causes of emergency department visits and hospital admissions within 10 days of COVID‐19 vaccination. Patients who received first or second doses of COVID‐19 vaccines and presented to the emergency department (ED), as well as those admitted to the hospitals or intensive care units (ICUs) were included. Causes of ED, hospital, and ICU admissions and discharges were collected based on the International Classification of Diseases, Tenth Revision (ICD‐10) coding system. Results Between December 2020 and March 2021, 1842 patients visited the ED within 10 days of COVID‐19 vaccine administration. The mean age was 70.3 years. Overall, 1221 patients presented after the first dose of the vaccine and 653 after the second dose. Trauma (14.9%), hypertensive emergency/urgency (7.8%), generalized pain and arthralgia (5.7%), and chest pain (4.4%) were the most common causes of presentation to the ED. Of all ED presentations, mortality rate was at 2.2% (41 patients) with a median follow‐up time of 68.0 days, versus 2.6% in unvaccinated ED patients. Postvaccination acute hypoxemic respiratory failure (46.3%), septic shock (24.4%), and cardiogenic shock (12.2%) were the most common causes of death. Conclusion Although reported AEs are not necessarily caused by the vaccination, this study provides further information about possible AEs after COVID‐19 immunization, especially those requiring hospital admission. This study also supports prior data that serious AEs post vaccination are much lower than primary COVID‐19 infections. Further studies are needed to investigate causalities between vaccines and reported AEs across all age groups.

Summary: In traumatic brain injury (TBI), a diversity of brain resident and peripherally derived myeloid cells have the potential to worsen damage and/or to assist in healing. We define the heterogeneity of microglia and macrophage phenotypes during TBI in wild-type (WT) mice and Ccr2−/− mice, which lack macrophage influx following TBI and are resistant to brain damage. We use unbiased single-cell RNA sequencing methods to uncover 25 microglia, monocyte/macrophage, and dendritic cell subsets in acute TBI and normal brains. We find alterations in transcriptional profiles of microglia subsets in Ccr2−/− TBI mice compared to WT TBI mice indicating that infiltrating monocytes/macrophages influence microglia activation to promote a type I IFN response. Preclinical pharmacological blockade of hCCR2 after injury reduces expression of IFN-responsive gene, Irf7, and improves outcomes. These data extend our understanding of myeloid cell diversity and crosstalk in brain trauma and identify therapeutic targets in myeloid subsets.

Summary: We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

Background: In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. Methods: To evaluate the impact of ATRX loss of function (LoF) in neuroblastoma, we utilized CRISPR-Cas9 gene editing to generate neuroblastoma cell lines isogenic for ATRX. We used these and other models to identify therapeutically exploitable synthetic lethal vulnerabilities associated with ATRX LoF. Findings: In isogenic cell lines, we found that ATRX inactivation results in increased DNA damage, homologous recombination repair (HRR) defects and impaired replication fork processivity. In keeping with this, high-throughput compound screening showed selective sensitivity in ATRX mutant cells to multiple PARP inhibitors and the ATM inhibitor KU60019. ATRX mutant cells also showed selective sensitivity to the DNA damaging agents, sapacitabine and irinotecan. HRR deficiency was also seen in the ATRX deleted CHLA-90 cell line, and significant sensitivity demonstrated to olaparib/irinotecan combination therapy in all ATRX LoF models. In-vivo sensitivity to olaparib/irinotecan was seen in ATRX mutant but not wild-type xenografts. Finally, sustained responses to olaparib/irinotecan therapy were seen in an ATRX deleted neuroblastoma patient derived xenograft. Interpretation: ATRX LoF results in specific DNA damage repair defects that can be therapeutically exploited. In ATRX LoF models, preclinical sensitivity is demonstrated to olaparib and irinotecan, a combination that can be rapidly translated into the clinic. Funding: This work was supported by Christopher's Smile, Neuroblastoma UK, Cancer Research UK, and the Royal Marsden Hospital NIHR BRC.

An efficient and facile route for the immobilization of silver (Ag) nanoparticles (NPs) in anion exchange resin beads with different silver loading is proposed. In this method, BH4− ions were first introduced into chloride-form resin through an ion exchange process with Cl− ions, followed by in-situ chemical reduction of Ag+ ions at the surface of the resin to form metallic Ag nanoparticles. Morphology and structure of the resulting Ag-resin nanocomposites were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), Fourier transform infra-red (FTIR), inductively coupled plasma-optical emission spectrometry (ICP-OES), and thermogravimetry analysis (TGA). The results confirmed the presence of smaller diameter Ag NPs incorporated into the resin beads having an average diameter on the order of 10 nm with a few Ag NP clusters of 20–100 nm. The nanoparticles were homogeneously distributed throughout the resin. There were no dramatic increases in average particle sizes even at very high Ag loadings. The resin retained its structure and stability, allowing higher stability of immobilized AgNPs than the colloidal ones. The Ag-loaded resins made with 50 mM AgNO3 were tested for antibacterial activity in vitro against Escherichia coli (E. coli) as a model microbial contaminant in water. Results showed greater than 99% bacterial inhibition within 3 h of exposure. The resin form offers greater ease of handling, long-term storage at room temperature, reusability in repeated reactions, and reduces the risk of environmental contamination.

Anticipatory thinking is a critical cognitive skill for successfully navigating complex, ambiguous systems in which individuals must analyze system states, anticipate outcomes, and forecast future events. For example, in military planning, intelligence analysis, business, medicine, and social services, individuals must use information to identify warnings, anticipate a spectrum of possible outcomes, and forecast likely futures in order to avoid tactical and strategic surprise. Existing methods for examining anticipatory thinking skill have relied upon task-specific behavioral measures or are resource-intensive, both of which are challenging to scale. Given the increasing importance of anticipatory thinking in many domains, developing a generic assessment of this skill and identifying the underlying cognitive mechanisms supporting it are paramount. The work reported here focuses on the development and validation of the anticipatory thinking assessment (ANTA) for measuring the divergent generative process of anticipatory thinking. Two-hundred and ten participants completed the ANTA, which required them to anticipate possible risks, opportunities, trends, or other uncertainties associated with a focal topic. Responses to the anticipatory thinking and divergent thinking tasks were rated by trained raters on a five-point scale according to the uniqueness, specificity, and remoteness of responses. Results supported the ANTA’s construct validity, convergent validity, and discriminant validity. We also explored the relationship between the ANTA scores and certain psychological traits and cognitive measures (need for cognition, need for closure, and mindfulness). Our findings suggest that the ANTA is a psychometrically valid instrument that may help researchers investigate anticipatory thinking in new contexts.

The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms.

Poly ADP-ribosylation (PARylation) is a highly dynamic post-translation protein modification, but most methods only detect stable PARylation events. Here the authors develop a split-GFP-based sensor for PARylation detection in live cells and use it to identify a new centrosomal PARylation target.

Abstract Background Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam. Methods/design This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay. Discussion This study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay. Trial registration ClinicalTrials.gov, NCT02966392. Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.

Abstract Background The High-Level Commission on Health Employment and Economic Growth released its report to the United Nations Secretary-General in September 2016. It makes important recommendations that are based on estimates of over 40 million new health sector jobs by 2030 in mostly high- and middle-income countries and a needs-based shortage of 18 million, mostly in low- and middle-income countries. This paper shows how these key findings were developed, the global policy dilemmas they raise, and relevant policy solutions. Methods Regression analysis is used to produce estimates of health worker need, demand, and supply. Projections of health worker need, demand, and supply in 2030 are made under the assumption that historical trends continue into the future. Results To deliver essential health services required for the universal health coverage target of the Sustainable Development Goal 3, there will be a need for almost 45 million health workers in 2013 which is projected to reach almost 53 million in 2030 (across 165 countries). This results in a needs-based shortage of almost 17 million in 2013. The demand-based results suggest a projected demand of 80 million health workers by 2030. Conclusions Demand-based analysis shows that high- and middle-income countries will have the economic capacity to employ tens of millions additional health workers, but they could face shortages due to supply not keeping up with demand. By contrast, low-income countries will face both low demand for and supply of health workers. This means that even if countries are able to produce additional workers to meet the need threshold, they may not be able to employ and retain these workers without considerably higher economic growth, especially in the health sector.

Abstract Background Ventilator-associated respiratory infection (VARI) is a significant problem in resource-restricted intensive care units (ICUs), but differences in casemix and etiology means VARI in resource-restricted ICUs may be different from that found in resource-rich units. Data from these settings are vital to plan preventative interventions and assess their cost-effectiveness, but few are available. Methods We conducted a prospective observational study in four Vietnamese ICUs to assess the incidence and impact of VARI. Patients ≥ 16 years old and expected to be mechanically ventilated > 48 h were enrolled in the study and followed daily for 28 days following ICU admission. Results Four hundred fifty eligible patients were enrolled over 24 months, and after exclusions, 374 patients’ data were analyzed. A total of 92/374 cases of VARI (21.7/1000 ventilator days) were diagnosed; 37 (9.9%) of these met ventilator-associated pneumonia (VAP) criteria (8.7/1000 ventilator days). Patients with any VARI, VAP, or VARI without VAP experienced increased hospital and ICU stay, ICU cost, and antibiotic use (p

Abstract Background In their adoption of WHA resolution 69.19, World Health Organization Member States requested all bilateral and multilateral initiatives to conduct impact assessments of their funding to human resources for health. The High-Level Commission for Health Employment and Economic Growth similarly proposed that official development assistance for health, education, employment and gender are best aligned to creating decent jobs in the health and social workforce. No standard tools exist for assessing the impact of global health initiatives on the health workforce, but tools exist from other fields. The objectives of this paper are to describe how a review of grey literature informed the development of a draft health workforce impact assessment tool and to introduce the tool. Method A search of grey literature yielded 72 examples of impact assessment tools and guidance from a wide variety of fields including gender, health and human rights. These examples were reviewed, and information relevant to the development of a health workforce impact assessment was extracted from them using an inductive process. Results A number of good practice principles were identified from the review. These informed the development of a draft health workforce impact assessment tool, based on an established health labour market framework. The tool is designed to be applied before implementation. It consists of a relatively short and focused screening module to be applied to all relevant initiatives, followed by a more in-depth assessment to be applied only to initiatives for which the screening module indicates that significant implications for HRH are anticipated. It thus aims to strike a balance between maximising rigour and minimising administrative burden. Conclusion The application of the new tool will help to ensure that health workforce implications are incorporated into global health decision-making processes from the outset and to enhance positive HRH impacts and avoid, minimise or offset negative impacts.

We investigated the consequences of colistin use in backyard chicken farms in Vietnam by examining the prevalence of mcr-1 in fecal samples from chickens and humans. Detection of mcr-1–carrying bacteria in chicken samples was associated with colistin use and detection in human samples with exposure to mcr-1–positive chickens.

Mutations in the BAF SWI/SNF complex subunits are frequent in cancers but selective therapeutic approaches are not available yet. Here, the authors demonstrate that defects ofARID1Aand other subunits sensitizes cancer cells to the DNA checkpoint kinase inhibitor ATR in a synthetic lethal manner.

An amendment to this paper has been published and can be accessed via the original article.

One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors.

In the Mekong Delta of Vietnam, farmers use large quantities of antimicrobials to raise small-scale chicken flocks, often including active ingredients regarded of “critical importance’” by the World Health Organization. Due to limitations in laboratory capacity, the choice of antimicrobials normally does not follow any empirical criteria of effectiveness. The aim of this study was to highlight non-critically important antimicrobials against which chicken pathogens are likely to be susceptible as a basis for treatment guidelines. Microtiter broth dilution method was performed to determine the minimal inhibitory concentration (MIC) of 12 commonly used antimicrobials for 58 isolates, including Ornithobacterium rhinotracheale (ORT) (n = 22), Gallibacterium anatis (n = 19), and Avibacterium endocarditidis (n = 17). Unfortunately, internationally accepted breakpoints for resistance in these organisms do not exist. We drew tentative epidemiological cut-offs (TECOFFs) for those antimicrobial-pathogen combinations where MIC distributions suggested the presence of a distinct non-wild-type population. Based on the observed results, doxycycline would be the drug of choice for A.endocarditidis (11.8% presumptive non-wild type) and G. anatis infections (5.3% presumptive non-wild type). A total of 13.6% ORT isolates were non-wild type with regards to oxytetracycline, making it the drug of choice against this pathogen. This study illustrates the challenges in interpreting susceptibility testing results and the need to establish internationally accepted breakpoints for veterinary pathogens.

Data concerning intensive care unit (ICU)-acquired bacterial colonization and infections are scarce from low and middle-income countries (LMICs). ICU patients in these settings are at high risk of becoming colonized and infected with antimicrobial-resistant organisms (AROs). We conducted a prospective observational study at the Ho Chi Minh City Hospital for Tropical Diseases, Vietnam from November 2014 to January 2016 to assess the ICU-acquired colonization and infections, focusing on the five major pathogens in our setting: Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Klebsiella spp., Pseudomonas spp. and Acinetobacter spp., among adult patients with more than 48 hours of ICU stay. We found that 61.3% (223/364) of ICU patients became colonized with AROs: 44.2% (161/364) with rectal ESBL-producing E. coli and Klebsiella spp.; 30.8% (40/130) with endotracheal carbapenemase-producing Acinetobacter spp.; and 14.3% (52/364) with nasal methicillin-resistant S. aureus. The incidence rate of ICU patients becoming colonized with AROs was 9.8 (223/2,276) per 100 patient days. Significant risk factor for AROs colonization was the Charlson Comorbidity Index score. The proportion of ICU patients with HAIs was 23.4% (85/364), and the incidence rate of ICU patients contracting HAIs was 2.3 (85/3,701) per 100 patient days. The vascular catheterization (central venous, arterial and hemofiltration catheter) was significantly associated with hospital-acquired bloodstream infection. Of the 77 patients who developed ICU-acquired infections with one of the five specified bacteria, 44 (57.1%) had prior colonization with the same organism. Vietnamese ICU patients have a high colonization rate with AROs and a high risk of subsequent infections. Future research should focus on monitoring colonization and the development of preventive measures that may halt spread of AROs in ICU settings.

Multi-modality image-guided radiotherapy is the standard of care in contemporary cancer management; however, it is not common in preclinical settings due to both hardware and software limitations. Soft tissue lesions, such as orthotopic prostate tumors, are difficult to identify using cone beam computed tomography (CBCT) imaging alone. In this study, we characterized a research magnetic resonance (MR) scanner for preclinical studies and created a protocol for combined MR-CBCT image-guided small animal radiotherapy. Two in-house dual-modality, MR and CBCT compatible, phantoms were designed and manufactured using 3D printing technology. The phantoms were used for quality assurance tests and to facilitate end-to-end testing for combined preclinical MR and CBCT based treatment planning. MR and CBCT images of the phantoms were acquired utilizing a Varian 4.7 T scanner and XRad-225Cx irradiator, respectively. The geometry distortion was assessed by comparing MR images to phantom blueprints and CBCT. The corrected MR scans were co-registered with CBCT and subsequently used for treatment planning. The fidelity of 3D printed phantoms compared to the blueprint design yielded favorable agreement as verified with the CBCT measurements. The geometric distortion, which varied between -5% and 11% throughout the scanning volume, was substantially reduced to within 0.4% after correction. The distortion free MR images were co-registered with the corresponding CBCT images and imported into a commercial treatment planning software SmART Plan. The planning target volume (PTV) was on average 19% smaller when contoured on the corrected MR-CBCT images relative to raw images without distortion correction. An MR-CBCT based preclinical workflow was successfully designed and implemented for small animal radiotherapy. Combined MR-CBCT image-guided radiotherapy for preclinical research potentially delivers enhanced relevance to human radiotherapy for various disease sites. This novel protocol is wide-ranging and not limited to the orthotopic prostate tumor study presented in the study.

[This corrects the article DOI: 10.1371/journal.pone.0176578.].

In Vietnam, commercial disinfectants containing quaternary ammonium compounds (QACs) are commonly used in pig and poultry farms to maintain hygiene during production. We hypothesized that sustained exposure to sub-bactericidal concentrations of QAC-based disinfectants may result in increased levels of antimicrobial resistance (AMR) among Enterobacteriacea due to the increase of efflux pump expression. To test this hypothesis we exposed six antimicrobial-susceptible Escherichia coli (E. coli) and six antimicrobial-susceptible non-typhoidal Salmonella (NTS) isolates to increasing concentrations of a commonly used commercial disinfectant containing a mix of benzalkonium chloride and glutaraldehyde. Over the 12-day experiment, strains exhibited a significant change in their minimum inhibitory concentration (MIC) of the disinfectant product (mean increase of 31% (SD ± 40)) (p = 0.02, paired Wilcoxon test). Increases in MIC for the disinfectant product were strongly correlated with increases in MIC (or decreases in inhibition zone) for all antimicrobials (Pearson’s correlation coefficient 0.71–0.83, all p < 0.01). The greatest increases in MIC (or decreases in inhibition zone) were observed for ampicillin, tetracycline, ciprofloxacin, and chloramphenicol, and the smallest for gentamicin, trimethoprim/sulphamethoxazole. The treatment of 155 representative E. coli isolates from farmed and wild animals in the Mekong Delta (Vietnam) with phenyl-arginine beta-naphthylamide (PAβN), a generic efflux pump inhibitor, resulted in reductions in the prevalence of AMR ranging from 0.7% to 3.3% in these organisms, indicating a small contribution of efflux pumps on the observed prevalence of AMR on farms. These results suggest that the mass usage of commercial disinfectants, many of which contain QACs, is potentially a contributing factor on the generation and maintenance of AMR in animal production in Vietnam.

Making scientific data openly accessible and available for re-use is desirable to encourage validation of research results and/or economic development. Understanding what users may, or may not, do with data in online data repositories is key to maximizing the benefits of scientific data re-use. Many online repositories that allow access to scientific data indicate that data is “open,” yet specific usage conditions reviewed on 40 “open” sites suggest that there is no agreed upon understanding of what “open” means with respect to data. This inconsistency can be an impediment to data re-use by researchers and the public.

Background and study aims We analyzed NIS (National Inpatient Sample) database from 2007 – 2013 to determine if early esophagogastroduodenoscopy (EGD) (24 hours) for upper gastrointestinal bleeding improved the outcomes in terms of mortality, length of stay and costs. Patients and methods Patients were classified as having upper gastrointestinal hemorrhage by querying all diagnostic codes for the ICD-9-CM codes corresponding to upper gastrointestinal bleeding. For these patients, performance of EGD during admission was determined by querying all procedural codes for the ICD-9-CM codes corresponding to EGD; early EGD was defined as having EGD performed within 24 hours of admission and late EGD was defined as having EGD performed after 24 hours of admission. Results A total of 1,789,532 subjects with UGIH were identified. Subjects who had an early EGD were less likely to have hypovolemia, acute renal failure and acute respiratory failure. On multivariable analysis, we found that subjects without EGD were 3 times more likely to die during the admission than those with early EGD. In addition, those with late EGD had 50 % higher odds of dying than those with an early EGD. Also, after adjusting for all factors in the model, hospital stay was on average 3 and 3.7 days longer for subjects with no or late EGD, respectively, then for subjects with early EGD. Conclusion Early EGD (within 24 hours) is associated with lower in-hospital mortality, morbidity, shorter length of stay and lower total hospital costs.

[This corrects the article DOI: 10.1371/journal.pone.0149099.].

There is a paucity of data regarding initial bacterial colonization on admission to Intensive Care Units (ICUs) in low and middle-income countries (LMICs). Patients admitted to ICUs in LMICs are at high-risk of subsequent infection with antimicrobial-resistant organisms (AROs). We conducted a prospective, observational study at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam from November 2014 to January 2016 to assess the colonization and antimicrobial susceptibility of Staphylococcus aureus, Escherichia coli, Klebsiella spp., Pseudomonas spp. and Acinetobacter spp. among adult patients within 48 hours of ICU admission. We found the admission colonization prevalence (with at least one of the identified organisms) was 93.7% (785/838) and that of AROs was 63.1% (529/838). The colonization frequency with AROs among patients admitted from the community was comparable to those transferred from other hospitals (62.2% vs 63.8%). Staphylococcus aureus was the most commonly isolated bacteria from nasal swabs (13.1%, 110/838) and the methicillin-resistant Staphylococcus aureus nasal colonization prevalence was 8.6% (72/838). We isolated Escherichia coli from rectal swabs from almost all enrolled patients (88.3%, 740/838) and 52.1% (437/838) of patients were colonized by extended spectrum β-lactamase producing Escherichia coli. Notably, Klebsiella pneumoniae was the most frequently isolated bacteria from the tracheal swabs (11.8%, 18/153). Vietnamese ICU patients have a high rate of colonization with AROs and are thus at risk of subsequent infections with these organisms if good infection control practices are not in place.