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Automated instruments on board Volunteer Observing Ships (VOS) have provided high-frequency pCO2 measurements over basin-wide regions for a decade or so. In order to estimate regional air-sea CO2 fluxes, it is necessary to interpolate between in-situ measurements to obtain maps of the marine pCO2. Such an interpolation remains, however, a difficult task because VOS lines are too distant from each other to capture the high pCO2 variability. Relevant physical parameters available at large scale are thus necessary to serve as a guide to estimate the pCO2 values between the VOS lines. Satellites do not measure pCO2 but they give access to parameters related to the processes that control its variability, such as sea surface temperature (SST). In this paper we developed a method to compute pCO2 maps using satellite data (SST and CHL, the chlorophyll concentration), combined with a climatology of the mixed-layer depth (MLD). Using 15 401 measurements of surface pCO2 acquired in the North Atlantic between UK and Jamaica, between June 1994 and August 1995, we show that the parameterization of pCO2 as a function of SST, CHL and MLD yields more realistic pCO2 values than parameterizations that have been widely used in the past, based on SST, latitude, longitude or SST only. This parameterization was then used to generate seasonal maps of pCO2 over the North Atlantic. Results show that our approach yields the best marine pCO2 estimates, both in terms of absolute accuracy, when compared with an independent data set, and of geographical patterns, when compared to the climatology of Takahashi et al. (2002). This suggests that monitoring the seasonal variability of pCO2 over basin-wide regions is possible, provided that sufficient VOS lines are available.

BACKGROUND Whether extended culture allowing selection of embryos with high development potential has any advantage over cleavage-stage embryo transfer remains a matter of debate. Among the currently unsolved questions, the cumulative delivery rate resulting from fresh and frozen embryo transfers needs to be taken into account in both strategies. The aim of our study was, therefore, to compare the efficacy of single embryo transfer either on Day 2 or on Day 5/6 combining fresh and frozen embryo transfers. METHODS A prospective study including 478 couples assigned on a voluntary basis to undergo elective single embryo transfer (eSET, n = 243) on Day 2 or single blastocyst transfer (SBT, n = 235) on Day 5/6 was performed. The primary outcome measurement was the cumulative delivery rate including fresh and frozen–thawed cycles in both groups. RESULTS The delivery rate per cycle following fresh embryo transfer was significantly higher in the SBT group compared with the eSET group (P CONCLUSIONS The observed cumulative delivery rates in this study do not allow us to take a position in favor of SBT or eSET. An improvement in blastocyst cryopreservation may change this attitude. [ABSTRACT FROM AUTHOR]

Objective: To assess the long-term impact of the age of onset (AOO) of the first major depressive episode (MDE) according to 3 age groups and considering gender., Methods: Data were extracted from NESARC III, a representative U.S., Sample: We included 8053 participants with an MDE history in a cross-sectional and retrospective cohort study. We defined 3 AOO groups: childhood-onset (< 13 yo), adolescence-onset (13-18 yo), and adult-onset (> 18 yo). We compared sociodemographic characteristics, lifetime psychiatric disorders per DSM-5 criteria, and health-related quality of life (HRQOL) in each group and performed gender-stratified analyses., Results: Prevalence of childhood-onset MDE was 10.03 %, adolescence-onset was 14.12 %, and adult-onset was 75.85 %. Suicide attempts (AOR = 3.61; 95 % CI 2.90-4.50), anxiety disorders (AOR = 1.92; 95 % CI 1.62-2.27), and personality disorders (AOR = 3.08; 95 % CI 2.56-3.71) were more frequent in the childhood-onset than in the adult-onset one. Adolescence-onset group showed similar results. Physical Disability scale (p < 0.001) and Mental Disability scale (p < 0.001) were significantly lower in the childhood-onset group. Results were more nuanced in the adolescence-onset group. Women in childhood-onset and adolescence-onset groups had poorer outcomes than the adult-onset group. Differences were less pronounced in men., Limitations: Recall and classification biases inherent to survey design., Conclusion: Individuals, particularly women, who experienced their first MDE during childhood or adolescence exhibit higher lifetime psychiatric disorder prevalence and poorer HRQOL than those with adult-onset MDE. These findings highlight the importance of preventive measures, early diagnosis, and treatment of youth depression., Competing Interests: Declaration of competing interest None of the authors have any competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Castration-resistant metastatic prostate cancer remains lethal and a therapeutic challenge. Current strategies are geared towards the personalization of treatments based on the identification of relevant molecular targets, including genomic alterations involved in tumoral processes. Among these novel targeted therapies, poly-ADP-ribose polymerase inhibitors (PARPi), by blocking the action of enzymes involved in deoxyribonucleic acid (DNA) repair, induce the destruction of cells carrying defects in homologous recombination repair, often associated with alterations in genes involved in this mechanism. Thus, determining the presence of a molecular anomaly, particularly alterations in the BRCA1/2 genes, is a prerequisite for initiating PARPi monotherapy. In patients with metastatic castration-resistant prostate cancer , around 20-30 % carry this type of mutation. In this population, single-agent studies have demonstrated PARPi ability to prolong overall survival, and to improve symptom control, including pain. Other studies are underway to assess their effectiveness in combination with other therapies, and it already appears that association with new-generation hormone therapy can further prolong radiological progression-free survival, regardless of the mutation status of the genes involved in DNA repair, indicating a synergistic action between PARPi and new-generation hormone therapy., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis. Whether these T cells represent an antitumor response and how these T cells would be primed in the eye are both unknown. Herein, we characterized the T cells infiltrating primary UMs. CD8+ and Treg cells were more abundant in M3 than in D3 tumors. CD39+PD-1+CD8+ T cells were enriched in M3 tumors, suggesting specific responses to tumor antigen (Ag) as confirmed using HLA-A2:Melan-A tetramers. scRNAseq-VDJ analysis of T cells evidenced high numbers of proliferating CD39+PD1+CD8+ clonal expansions, suggesting in situ antitumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the antitumor responses in M3 and D3 tumors. Thus, tumor-Ag responses occur in localized UMs, raising the question of the priming mechanisms in the absence of known lymphatic drainage., (© 2024 Lucibello et al.)

The ocean absorbs a significant amount of carbon dioxide (CO 2 ) from the atmosphere, helping regulate Earth's climate. However, our knowledge of ocean CO 2 sink levels remains limited. This research focused on assessing daily changes in ocean CO 2 sink levels and air-sea CO 2 exchange, using a new technique. We used LiDAR technology, which provides continuous measurements during day and night, to estimate global ocean CO 2 absorption over 23 years. Our model successfully reproduced sea surface partial pressure of CO 2 data. The results suggest the total amount of CO 2 absorbed by oceans is higher at night than during the day. This difference arises from a combination of factors like temperatures, winds, photosynthesis, and respiration. Understanding these daily fluctuations can improve predictions of ocean CO 2 uptake. It may also help explain why current carbon budget calculations are not fully balanced-an issue scientists have grappled with. Overall, this pioneering study highlights the value of LiDAR's unique day-night ocean data coverage. The findings advance knowledge of ocean carbon cycles and their role in climate regulation. They underscore the need to incorporate day-night variability when assessing the ocean's carbon sink capacity., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Measuring the characteristics of seawater constituent is in great demand for studies of marine ecosystems and biogeochemistry. However, existing techniques based on remote sensing or in situ samplings present various tradeoffs with regard to the diversity, synchronism, temporal-spatial resolution, and depth-resolved capacity of their data products. Here, we demonstrate a novel oceanic triple-field-of-view (FOV) high-spectral-resolution lidar (HSRL) with an iterative retrieval approach. This technique provides, for the first time, comprehensive, continuous, and vertical measurements of seawater absorption coefficient, scattering coefficient, and slope of particle size distribution, which are validated by simulations and field experiments. Furthermore, it depicts valuable application potentials in the accuracy improvement of seawater classification and the continuous estimation of depth-resolved particulate organic carbon export. The triple-FOV HSRL with high performance could greatly increase the knowledge of seawater constituents and promote the understanding of marine ecosystems and biogeochemistry., (Copyright © 2023 Kai Zhang et al.)

Neonatal screening has excellent coverage in France. Data from the foreign literature raise questions about the informed consent to this screening. The Neonatal Screening and Informed Consent Dépistage Néonatal Information et Consentement Eclairé (DENICE) study was designed to assess whether information on neonatal screening provided for families in Brittany allows for informed consent. A qualitative methodology was chosen to collect parents' opinions on this topic. Twenty semi-structured interviews were conducted with twenty-seven parents whose children had positive neonatal screening for one of six diseases. The five main themes from the qualitative analysis were knowledge of neonatal screening, information received by parents, parental choice, the experience of the screening process, and parents' perspectives and wishes. Informed consent was weakened by parents' lack of knowledge regarding choice and the absence of a parent after birth. The study found that more information about screening during pregnancy would be preferable. The information should be repeated and accessible and should make it clear that neonatal screening is not mandatory, but informed consent should be obtained from parents who choose to screen their newborns.

The development of algorithms for remote sensing of water quality (RSWQ) requires a large amount of in situ data to account for the bio-geo-optical diversity of inland and coastal waters. The GLObal Reflectance community dataset for Imaging and optical sensing of Aquatic environments (GLORIA) includes 7,572 curated hyperspectral remote sensing reflectance measurements at 1 nm intervals within the 350 to 900 nm wavelength range. In addition, at least one co-located water quality measurement of chlorophyll a, total suspended solids, absorption by dissolved substances, and Secchi depth, is provided. The data were contributed by researchers affiliated with 59 institutions worldwide and come from 450 different water bodies, making GLORIA the de-facto state of knowledge of in situ coastal and inland aquatic optical diversity. Each measurement is documented with comprehensive methodological details, allowing users to evaluate fitness-for-purpose, and providing a reference for practitioners planning similar measurements. We provide open and free access to this dataset with the goal of enabling scientific and technological advancement towards operational regional and global RSWQ monitoring., (© 2023. The Author(s).)

Lidar techniques present a distinctive ability to resolve vertical structure of optical properties within the upper water column at both day- and night-time. However, accuracy challenges remain for existing lidar instruments due to the ill-posed nature of elastic backscatter lidar retrievals and multiple scattering. Here we demonstrate the high performance of, to the best of our knowledge, the first shipborne oceanic high-spectral-resolution lidar (HSRL) and illustrate a multiple scattering correction algorithm to rigorously address the above challenges in estimating the depth-resolved diffuse attenuation coefficient K d and the particulate backscattering coefficient b bp at 532 nm. HSRL data were collected during day- and night-time within the coastal areas of East China Sea and South China Sea, which are connected by the Taiwan Strait. Results include vertical profiles from open ocean waters to moderate turbid waters and first lidar continuous observation of diel vertical distribution of thin layers at a fixed station. The root-mean-square relative differences between the HSRL and coincident in situ measurements are 5.6% and 9.1% for K d and b bp , respectively, corresponding to an improvement of 2.7-13.5 and 4.9-44.1 times, respectively, with respect to elastic backscatter lidar methods. Shipborne oceanic HSRLs with high performance are expected to be of paramount importance for the construction of 3D map of ocean ecosystem., (© 2022. The Author(s).)

Water quality measures for inland and coastal waters are available as discrete samples from professional and volunteer water quality monitoring programs and higher-frequency, near-continuous data from automated in situ sensors. Water quality parameters also are estimated from model outputs and remote sensing. The integration of these data, via data assimilation, can result in a more holistic characterization of these highly dynamic ecosystems, and consequently improve water resource management. It is becoming common to see combinations of these data applied to answer relevant scientific questions. Yet, methods for scaling water quality data across regions and beyond, to provide actionable knowledge for stakeholders, have emerged only recently, particularly with the availability of satellite data now providing global coverage at high spatial resolution. In this paper, data sources and existing data integration frameworks are reviewed to give an overview of the present status and identify the gaps in existing frameworks. We propose an integration framework to provide information to user communities through the the Group on Earth Observations (GEO) AquaWatch Initiative. This aims to develop and build the global capacity and utility of water quality data, products, and information to support equitable and inclusive access for water resource management, policy and decision making., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Objectives: Older patients with cancer have increased risk for comorbidity, polypharmacy (PP) and drug related problems (DRP). The aim of this study was to assess the effect of a clinical pharmacist and geriatrician medication review (MR) among older outpatients with cancer to optimize management of comorbidities during comprehensive geriatric assessment (CGA)., Material and Methods: We conducted a single-center prospective study among older outpatients with cancer (≥75 years). A pharmacist consultation was added into CGA process. The clinical pharmacist detected and assessed PP and DRP such as potentially inappropriate medications (PIM) according to the Laroche French list and STOPP criteria, START criteria and adverse drug events (ADE) risk. After a multidisciplinary MR, the proposals for prescription modification were sent to general practitioners (GPs)., Results: Fifty-one consenting patients were recruited between May 2016 and March 2017, with a median age of 83 years. Prevalence of PP was 80.4%. 165 DRP were detected among 86% patients (median number of DRP = 3.0): 19.4% were misuse, 43.6% underuse, and 37.0% overuse. A significant decrease was observed in prevalence of PIM use (Laroche: 31.4% versus 5.9%, p = 0.002), START criteria (66.7% to 5.9%; P < 0.001) and ADE score (4.0 before MR versus 2.0 after, p = 0.023). A trend was observed for a lower number of medications (10.0 versus 8.0, p = 0.092) and on STOPP criteria prevalence (56.9% versus 31.4%, p = 0.12)., Conclusion: A clinical pharmacist and a geriatrician MR is effective to detect and reduce DRP in older outpatients with cancer., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In 2017, Field access was considerably limited in the Far North region of Cameroon due to the conflict. Médecins Sans Frontieres (MSF) in collaboration with Ministry of health needed to estimate the health situation of the populations living in two of the most affected departments of the region: Logone-et-Chari and Mayo-Sava., Methods: Access to health care and mortality rates were estimated through cell phone interviews, in 30 villages (clusters) in each department. Local Community Health Workers (CHWs) previously collected all household phone numbers in the selected villages and nineteen were randomly selected from each of them. In order to compare telephone interviews to face-to-face interviews for estimating health care access, and mortality rates, both methods were conducted in parallel in the town of Mora in the mayo Sava department. Access to food was assessed through push messages sent by the three main mobile network operators in Cameroon. Additionally, all identified legal health care facilities in the area were interviewed by phone to estimate attendance and services offered before the conflict and at the date of the survey., Results: Of a total of 3423 households called 43% were reached. Over 600,000 push messages sent and only 2255 were returned. We called 43 health facilities and reached 34 of them. In The town of Mora, telephone interviews showed a Crude Mortality Rate (CMR) at 0.30 (CI 95%: 0.16-0.43) death per 10,000-person per day and home visits showed a CMR at 0.16 (0.05-0.27), most other indicators showed comparable results except household composition (more Internally Displaced Persons by telephone). Phone interviews showed a CMR at 0.63 (0.29-0.97) death per 10,000-person per day in Logone-et-Chari, and 0.30 (0.07-0.50) per 10,000-person per day in Mayo-Sava. Among 86 deaths, 13 were attributed to violence (15%), with terrorist attacks being explicitly mentioned for seven deaths. Among 29 health centres, 5 reported being attacked and vandalized; 3 remained temporally closed; Only 4 reported not being affected., Conclusion: Telephone interviews are feasible in areas with limited access, although special attention should be paid to the initial collection of phone numbers. The use of text messages to collect data was not satisfactory is not recommended for this purpose. Mortality in Logone-et-Chari and Mayo-Sava was under critical humanitarian thresholds although a considerable number of deaths were directly related to the conflict.

Competing Interests: Competing interests: None declared.

Water pixel extraction and correction of the atmospheric signal represent prerequisite steps prior to applying algorithms dedicated to the assessment of water quality of natural surface water bodies. The recent multiplication of medium spatial resolution sensors (10-60 m) provides the required constellation to monitoring bio-optical and biogeochemical parameters of surface waters at the relevant spatial-temporal scales. Here we present a new approach to identify water pixels and to extract the atmospheric contribution to the top of atmosphere signal measured by the NAOMI sensor on board the first Vietnamese satellite, VNREDSat-1. After verifying the TOA calibration of NAOMI through a vicarious calibration exercise, we adapt a recent water pixel extraction algorithm (WiPE) to NAOMI, and develop a new atmospheric correction algorithm (referred to as red-NIR) based on the use of the red and NIR bands (the only bands available for that purpose on NAOMI) and spectral relationships. The evaluation of red-NIR with a match-up data set gathering remote sensing reflectance, R rs , measurements performed at the AERONET-OC stations in moderately turbid waters indicates excellent performance in the blue and green part of the spectrum (similar to the performances reached by the SeaDAS NIR-SWIR algorithms) and lower accuracy in the red. Intercomparison of simultaneous images collected by NAOMI and OLI over a more turbid water body shows an excellent agreement between the NAOMI-R rs estimated by the present processing, and the OLI-R rs estimated from the ACOLITE algorithm. This approach will allow sensors that do not have SWIR bands, such as SPOT-6 and -7, to be processed, making their data exploitation available for long-term temporal analyses.

Background: Atraumatic needles are proposed to lower complication rates after lumbar puncture (LP). Only a minority of physicians use such needles. Here we aimed to assess the impact of specific training in LP during clinical clerkship on the proportion of medical students using atraumatic needles., Methods: We performed a case-control study comparing medical students undergoing clinical clerkship and students undergoing specific LP training. The 176 students of a class underwent training in LP just before beginning their clinical rotations. This training consisted of 45 minutes of theoretical training and a 90-minute practical session with a dummy. Twenty students were selected from the class at random, and their competence was assessed with a multiple choice questionnaire (MCQ) and an objective structured clinical examination (OSCE), nine months after the specific training. These 20 cases were compared with 20 students randomly selected from a class of 180 students who had not undergone specific training in LP and were at the end of their clinical clerkship., Results: We found that 60% of the students with specific training and 25% of those with classic clinical training used an atraumatic needle during the OSCE (p = 0.025). The mean MCQ (/100) scores obtained were 57±15 and 60±15 for the specific and classic training groups, respectively (p = 0.35). Overall OSCE score was similar in the two groups (63.5±9.3 vs. 65.8±9.3; p = 0.20)., Conclusion: Very few practicing physicians use atraumatic needles, which limits the teaching of their use to medical students. Specific training durably increases the use of appropriate needles., Competing Interests: XM reports fees from Teva, Sanofi-Genzyme, Merck-Serono, Novartis, Roche, Biogen and non-financial support from Sanofi-Pasteur-MSD, GSK, Astra Zeneca, and Pfizer, not relating to the submitted work. BP has nothing to disclose. CJ has nothing to disclose. AS has nothing to disclose. PC reports consultancy fees, speaker fees, research grants (non-personal), or honoraria from Novartis, Biogen, Merck, Roche, Medday, Actelion, Teva and Genzyme Sanofi, not relating to the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

This paper reviews the state of the art of protocols for the measurement of downwelling irradiance in the context of Fiducial Reference Measurements (FRM) of water reflectance for satellite validation. The measurement of water reflectance requires the measurement of water-leaving radiance and downwelling irradiance just above water. For the latter, there are four generic families of method, using: (1) an above-water upward-pointing irradiance sensor; (2) an above-water downward-pointing radiance sensor and a reflective plaque; (3) a Sun-pointing radiance sensor (sunphotometer); or (4) an underwater upward-pointing irradiance sensor deployed at different depths. Each method-except for the fourth, which is considered obsolete for the measurement of above-water downwelling irradiance-is described generically in the FRM context with reference to the measurement equation, documented implementations, and the intra-method diversity of deployment platform and practice. Ideal measurement conditions are stated, practical recommendations are provided on best practice, and guidelines for estimating the measurement uncertainty are provided for each protocol-related component of the measurement uncertainty budget. The state of the art for the measurement of downwelling irradiance is summarized, future perspectives are outlined, and key debates such as the use of reflectance plaques with calibrated or uncalibrated radiometers are presented. This review is based on the practice and studies of the aquatic optics community and the validation of water reflectance, but is also relevant to land radiation monitoring and the validation of satellite-derived land surface reflectance., Competing Interests: Conflicts of Interest: The first author is involved in the design of systems based on the “irradiance sensor” method and in the acquisition of data using the “irradiance sensor” and “sunphotometer” methods. Other co-authors are involved in the acquisition of data using the “irradiance sensor”, the “reflectance plaque” and the “sunphotometer” methods. The funders had no role in the design of the study other than the drafting of the FRM4SOC project Statement of Work, which states that such a protocol review should be performed. The funders had no role in the collection, analyses, or interpretation of data or in the writing of the manuscript other than general project monitoring and encouragement. The funders did encourage publication of this review in order to ensure that high quality measurements of known uncertainty are available for the validation of the satellite missions they design and operate. None of these interests is considered to be conflictual or to inappropriately influence the recommendations expressed here.

The use of oral cholera vaccine (OCV) has increased since 2011, when Shanchol, the first OCV suitable for large-scale use, became available. Médecins Sans Frontières considers OCVs an essential cholera outbreak control tool and has contributed to generating new evidence on OCV use in outbreaks. We showed that large-scale mass campaigns are feasible during outbreaks, documented high short-term effectiveness and showed that vaccines are likely safe in pregnancy. We found that a single-dose regimen has high short-term effectiveness, making rapid delivery of vaccine during outbreaks easier, especially given the on-going global vaccine shortage. Despite progress, OCV has still not been used widely in some of the largest recent outbreaks and thousands of cholera deaths are reported every year. While working towards improving our tools to protect those most at-risk of cholera, we must strive to use all available effective interventions in efficient ways, including OCV, to prevent avoidable deaths today.

Background: Universal antiretroviral therapy (ART) for all pregnant/ breastfeeding women living with Human Immunodeficiency Virus (HIV), known as Prevention of mother-to child transmission of HIV (PMTCT) Option B+ (PMTCTB+), is being scaled up in most countries in Sub-Saharan Africa. In the transition to PMTCTB+, many countries face challenges with proper implementation of the HIV care cascade. We aimed to describe the feasibility of a PMTCTB+ approach in the public health sector in Swaziland., Methods: Lifelong ART was offered to a cohort of HIV+ pregnant women aged ≥16 years at the first antenatal care (ANC1) visit in 9 public sector facilities, between 01/2013 and 06/2014. The study enrolment period was divided into 3 phases (early: 01-06/2013, mid: 07-12/2013 and late: 01-06/2014) to account for temporal trends. Kaplan-Meier estimates and Cox proportional-hazards regression models were applied for ART initiation and attrition analyses., Results: Of 665 HIV+ pregnant women, 496 (74.6%) initiated ART. ART initiation increased in later study enrolment phases (mid: aHR: 1.41; later: aHR: 2.36), and decreased at CD4 ≥ 500 (aHR: 0.69). 52.9% were retained in care at 24 months. Attrition was associated with ANC1 in the third trimester (aHR: 2.37), attending a secondary care facility (aHR: 1.98) and ART initiation during later enrolment phases (mid aHR: 1.48; late aHR: 1.67). Of 373 women eligible, 67.3% received a first VL. 223/251 (88.8%) were virologically suppressed (< 1000 copies/mL). Of 670 infants, 53.6% received an EID test, 320/359 had a test result recorded and of whom 7 (2.2%) were HIV+., Conclusions: PMTCTB+ was found to be feasible in this setting, with high rates of maternal viral suppression and low transmission to the infant. High treatment attrition, poor follow-up of mother-baby pairs and under-utilisation of VL and EID testing are important programmatic challenges.

Introduction: In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area., Methodology/principal Findings: Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3)., Conclusions/significance: Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

The AhR is a cytosolic ligand-dependent transcription factor activated by both endogenous and exogenous chemicals. It can regulate expression of many target genes including some inflammatory cytokines and chemokines. To date AhR implication in the regulation of inflammatory cytokines and chemokines at human cerebral endothelium has not been addressed. In the present study, we investigated whether AhR could regulate the expression of two pro-inflammatory cytokines and one chemokine i.e. IL-1β, IL-6 and IL-8 in the hCMEC/D3 human cerebral microvascular endothelial cell line. Exposure to TCDD increased IL-1β mRNA expression levels in hCMEC/D3. By using small interfering RNA against AhR we demonstrated that TCDD effects on IL-1β expression were mediated through AhR activation. Regarding IL-6 and IL-8, TCDD exposure had little or no effect on their mRNA levels in hCMEC/D3. In conclusion, our findings suggest that AhR-mediated IL-1β regulation in cerebral endothelium could induce BBB breakdown and contribute to the pathogenesis of a variety of neurologic disorders., (Copyright © 2017. Published by Elsevier Ltd.)

Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Cholera rapid diagnostic tests (RDT) could play a central role in outbreak detection and surveillance in low-resource settings, but their modest performance has hindered their broad adoption. The addition of an enrichment step may improve test specificity. We describe the results of a prospective diagnostic evaluation of the Crystal VC RDT (Span Diagnostics, India) with enrichment step and of culture, each compared to polymerase chain reaction (PCR), during a cholera outbreak in South Sudan. RDTs were performed on alkaline peptone water inoculated with stool and incubated for 4-6 hours at ambient temperature. Cholera culture was performed from wet filter paper inoculated with stool. Molecular detection of Vibrio cholerae O1 by PCR was done from dry Whatman 903 filter papers inoculated with stool, and from wet filter paper supernatant. In August and September 2015, 101 consecutive suspected cholera cases were enrolled, of which 36 were confirmed by PCR. The enriched RDT had 86.1% (95% CI: 70.5-95.3) sensitivity and 100% (95% CI: 94.4-100) specificity compared to PCR as the reference standard. The sensitivity of culture versus PCR was 83.3% (95% CI: 67.2-93.6) for culture performed on site and 72.2% (95% CI: 54.8-85.8) at the international reference laboratory, where samples were tested after an average delay of two months after sample collection, and specificity was 98.5% (95% CI: 91.7-100) and 100% (95% CI: 94.5-100), respectively. The RDT with enrichment showed performance comparable to that of culture and could be a sustainable alternative to culture confirmation where laboratory capacity is limited., Competing Interests: The authors have declared that no competing interests exist.

Background: Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention., Methods: We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India)., Findings: Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0)., Interpretation: One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings., Funding: Médecins Sans Frontières., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)