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Abstract Background The objective was to assess the agreement between therapeutic proposals derived from basic critical care echocardiography performed by novice operators in ultrasonography after a limited training (residents) and by experts considered as reference. Secondary objectives were to assess the agreement between operators’ answers to simple clinical questions and the concordance between basic two-dimensional measurements. Methods This observational, prospective, single-center study was conducted over a 3-year period in a medical-surgical intensive care unit. Adult patients with acute circulatory and/or respiratory failure requiring a transthoracic echocardiography (TTE) examination were studied. In each patient, a TTE was performed by a resident novice in ultrasonography after a short training program and by an expert, independently but within 1 h and in random order. Each operator addressed standardized simple clinical questions and subsequently proposed a therapeutic strategy based on a predefined algorithm. Results Residents performed an average of 33 TTE studies in 244 patients (156 men; age: 63 years [52–74]; SAPS2: 45 [34–59]; 182 (75%) mechanically ventilated). Agreement between the therapeutic proposals of residents and experienced operators was good-to-excellent. The concordance was excellent for suggesting fluid loading, inotrope or vasopressor support (all Kappa values > 0.80). Inter-observer agreement was only moderate when considering the indication of negative fluid balance (Kappa: 0.65; 95% CI 0.50–0.80), since residents proposed diuretics in 23 patients (9.5%) while their counterparts had the same suggestion in 35 patients (14.4%). Overall agreement of responses to simple clinical questions was also good-to-excellent. Intraclass correlation coefficient exceeded 0.75 for measurement of ventricular and inferior vena cava size. Conclusions A limited training program aiming at acquiring the basic level in critical care echocardiography enables ICU residents novice in ultrasonography to propose therapeutic interventions with a good-to-excellent agreement with experienced operators.

Introduction: Cancers of unknown primary are aggressive and rare malignancies with a complex diagnosis and management. Here we present a case in which imaging, pathology, and molecular biology did not match for a specific tumor site and the importance of a multidisciplinary team for these complicated cases. Case Presentation: A man in his 70s with strong smoking history under workup for suspicion of metastatic lung cancer underwent lung mass biopsy. Immunohistochemical stains corresponded to hepatocellular/cholangiocarcinoma or germ cell tumor; however, dedicated liver and testicular studies including imaging and iscochrome 12p FISH were negative. Additionally, somatic variant profiling was not specific for any malignancy nor targetable variants. Given the pattern of disease, risk factors, and patient history, the patient received treatment for lung adenocarcinoma (carboplatin, pemetrexed, and pembrolizumab). The patient had a drastic improvement in dyspnea, weight gain, and was able to return to work. Conclusion: This report describes a case in which immunohistochemistry and molecular profiling did not identify the tissue of origin and highlights the importance of a multidisciplinary team to reach a diagnosis and guide treatment without delaying patient care in patients with these diagnoses.

Abstract This study presents the development of a so‐called Turbulent Kinetic Energy (TKE)‐l, or TKE‐l, parameterization of the diffusion coefficients for the representation of turbulent diffusion in neutral and stable conditions in large‐scale atmospheric models. The parameterization has been carefully designed to be completely tunable in the sense that all adjustable parameters have been clearly identified and the number of parameters has been minimized as much as possible to help the calibration and to thoroughly assess the parametric sensitivity. We choose a mixing length formulation that depends on both static stability and wind shear to cover the different regimes of stable boundary layers. We follow a heuristic approach for expressing the stability functions and turbulent Prandlt number in order to guarantee the versatility of the scheme and its applicability for planetary atmospheres composed of an ideal and perfect gas such as that of Earth and Mars. Particular attention has been paid to the numerical stability and convergence of the TKE equation at large time steps, an essential prerequisite for capturing stable boundary layers in General Circulation Models (GCMs). Tests, parametric sensitivity assessments and preliminary tuning are performed on single‐column idealized simulations of the weakly stable boundary layer. The robustness and versatility of the scheme are assessed through its implementation in the Laboratoire de Météorologie Dynamique Zoom GCM and the Mars Planetary Climate Model and by running simulations of the Antarctic and Martian nocturnal boundary layers.

Objective To describe antibiotic prescribing practices using the WHO AWaRe (Access, Watch, Reserve) classification in West African children under 5 years of age attending public primary health centres (PHCs).Design Cross-sectional study.Setting The AIRE project implemented the systematic use of pulse oximetry into integrated management of childhood illness consultations in West African countries (Burkina Faso, Guinea, Mali and Niger). We described antibiotic prescriptions for outpatient children at 16 PHCs and for severe cases referred at district hospitals.Patients Between 14 June 2021 and 19 June 2022, 15 854 outpatients were included: 968 neonates and young infants (0–28 days) and 14 886 children (2–59 months). Among them, 78 (8.1%) neonates and young infants and 385 (2.6%) children were hospitalised. We evaluated 58 hospitalised neonates and young infants and 275 hospitalised children, respectively.Main outcome measures Frequency of antibiotic prescriptions according to the AWaRe classification recommended by WHO.Results At the PHC level, proportions of neonates and young infants with ≥1 antibiotic prescription were 83%, 62%, 71% and 59% in Burkina Faso, Guinea, Mali and Niger, respectively. A total of 805 antibiotics were prescribed (85% Access and 13% Watch). The proportions of children with ≥1 antibiotic prescription reached 71%, 66%, 63% and 36% in Burkina Faso, Guinea, Mali and Niger, respectively. Out of the 9630 antibiotics prescribed, 93% were Access (mainly amoxicillin), and 7% Watch. At the hospital level, Watch antibiotics were mainly prescribed for severe cases referred. No Reserve antibiotics were prescribed.Conclusions High proportions of antibiotics were prescribed to outpatient children included, the appropriateness of which needs further study. Nevertheless, in every country, the proportion prescribed in the Access group reached the minimum threshold of 60% of all antibiotic prescriptions, as recommended by WHO.Trial registration number PACTR202206525204526.

Abstract Background Coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been proposed in this setting, but optimal criteria to select target patients remain unknown. Our hypothesis is that evaluation of right ventricular (RV) function could be helpful. The aims of our study were to report the incidence and outcomes of patients eligible for ECMO according to EOLIA criteria, and to identify a subgroup of patients with RV injury, which could be a target for ECMO. Methods Retrospective observational study involving 3 French intensive care units (ICUs) of teaching hospitals. Patients with confirmed SARS-CoV-2 infection between March 2020 and March 2021, presenting ARDS and with available echocardiography, were included. Patients were classified in three groups according to whether or not they met the EOLIA criteria and the presence of RV injury (RVI) (“EOLIA −”, “EOLIA + RVI −” and “EOLIA + RVI + ”). RVI was defined by the association of RV to left ventricular end-diastolic area ratio > 0.8 and paradoxical septal motion. Kaplan–Meier survival curves were used to analyze outcome as well as a Cox model for 90 day mortality. Results 915 patients were hospitalized for COVID-19, 418 of them with ARDS. A total of 283 patients with available echocardiography were included. Eighteen (6.3%) patients received ECMO. After exclusion of these patients, 107 (40.5%) were classified as EOLIA −, 126 (47.5%) as EOLIA + RVI −, and 32 (12%) as EOLIA + RVI + . Ninety-day mortality was 21% in the EOLIA-group, 44% in the EOLIA + RVI-group, and 66% in the EOLIA + RVI + group (p

Abstract A second autologous stem‐cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti‐CD38 and immunotherapy, its role remains debated. We conducted a real‐life study in 10 French centers (1996–2017) involving 267 RMM patients receiving ASCT2. The median age was 61 years, with 49% females. Most patients received melphalan 200 mg/m² before ASCT2, with low early mortality (1%). Very good partial response or better (VGPR+) rate post ASCT2 was 78%. Post ASCT2, 48% received consolidation therapy and 40% maintenance therapy. Median event‐free survival (EFS) after ASCT2 was 2.6 years (95% confidence interval [CI]: 2.3–2.8), and 2‐year EFS estimate was 63% (95% CI: 57–70). Median overall survival (OS) was 8.1 years (95% CI: 5.9–NA), and 2‐year OS estimate was 92% (95% CI: 88–95). Multivariate analysis revealed that VGPR+ status and maintenance therapy post ASCT2 were associated with better EFS (hazard ratio [HR]: 0.6; 95% CI: 0.3–0.9, p = 0.012 and HR: 0.4; 95% CI: 0.3–0.6, p

IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.

Studying precipitation falling over Antarctica is crucial as snowfall represents the main water input term for the polar cap. However, precipitation observations still remain scarce – and, more particularly, in the atmospheric column – due to numerous experimental issues related to the white continent. This paper aims at helping to close this observation gap by presenting 7 years of Micro Rain Radar (Metek MRR-2) data at the Dumont d'Urville station in coastal Adélie Land, East Antarctica. Statistics are calculated on three radar variables (equivalent reflectivity, mean Doppler velocity and signal-to-noise ratio (SNR)) to outline the main characteristics of the radar dataset. Seasonal and interannual variabilities are also investigated, but no significant temporal trends are detected, except for the seasonal mean Doppler velocity, which is higher in summer and lower in winter. We then use the snowfall rate (S) data from a collocated snow gauge to estimate the MRR precipitation profile from the radar equivalent reflectivity (Ze) through a locally derived Ze–S relation. We find the relation Ze=43.3S0.88. The processing method used to obtain this relation, data quality and uncertainty considerations are discussed in the paper. In order to give an example of application of the dataset, a brief statistical comparison of the MRR precipitation rate along the vertical with model data from the ERA5 reanalysis and the LMDZ climate model is performed, which notably shows that models underestimate heavy precipitation events. All datasets are available on the PANGAEA database with the associated DOI: https://doi.org/10.1594/PANGAEA.962727 (Wiener et al., 2023).

Abstract Background Angioimmunoblastic T‐cell lymphoma (AITL) is one of the most frequent peripheral T‐cell lymphomas (PTCL) in western countries. Skin involvement is common and may reveal the malignancy. Despite its frequency, skin involvement in AITL has been poorly described. Objectives We aimed to analyze the cutaneous expression of PTCL of TFH origin and its prognostic impact. Methods We conducted a multicenter retrospective cohort study by retrieving histopathological reports including the mention ‘AITL’ or ‘PTCL with T‐follicular helper phenotype’ (PTCL‐TFH) from five French tertiary hospital centers. Results From 2000 to 2022, we reviewed 382 histopathological records and identified 52 AITL cases and 5 PTCL‐TFH cases with cutaneous involvement. Thirty‐two (56%) patients were males with a mean age of 63 years. Fifty‐six (98%) patients presented with lymphadenopathy, 32 (56%) splenomegaly and 17 (30%) hepatomegaly. B signs were present in 34 (60%) patients. Skin lesions were present on the lower limbs in 44 (77%) patients, trunk in 38 (67%) patients, upper limbs in 35 (61%) and head in 27 (47%). Macules and papules were the most frequent lesions found in 47 (82%) patients, followed by nodules in 10 (17%) patients, erythemato‐squamous plaques in 10 (17%) patients, purpura in 9 (16%), urticaria in 9 (16%) and blisters in 5 (9%) patients. Erythroderma affected seven patients (12%). A skin biopsy was taken in 50 patients and revealed a specific lymphomatous infiltrate in 36 cases. A dominant skin T‐cell clone was detected in 13 out of 17 (76%) patients. Among the 14 patients with a nonspecific dermatitis, various histopathological patterns were observed including interface dermatitis, psoriasiform dermatitis, vasculitis, bullous dermatitis, granulomatous dermatitis and thrombotic vasculopathy. After a median follow‐up of 24 months (range, 0–121 months), median overall survival was 121 months (95% CI, 25.2–NA). At last follow‐up, 33 patients (58%) were alive, 20 (35%) were in complete remission and 7 (12%) were in partial remission; 30 (53%) patients experienced at least one relapse, including nodal relapses in 24 (80%) cases and cutaneous relapses in 12 (40%). Conclusions This study revealed the deep heterogeneity of skin presentations in AITL. Atypical skin presentations were common and included blistering, purpuric and psoriasiform eruptions.

Abstract We have previously shown that intracardiac delivery of autologous CD34+ cells after acute myocardial infarction (AMI) is safe and leads to long term improvement. We are now conducting a multicenter, randomized, controlled Phase I/IIb study in post-AMI to investigate the safety and efficacy of intramyocardial injection of expanded autologous CD34+ cells (ProtheraCytes) (NCT02669810). Here, we conducted a series of in vitro studies characterizing the growth factor secretion, exosome secretion, gene expression, cell surface markers, differentiation potential, and angiogenic potential of ProtheraCytes clinical batches to develop a potency assay. We show that ProtheraCytes secrete vascular endothelial growth factor (VEGF) and its concentration is significantly correlated with the number of CD34+ cells obtained after expansion. ProtheraCytes also secrete exosomes containing proangiogenic miRNAs (126, 130a, 378, 26a), antiapoptotic miRNAs (21 and 146a), antifibrotic miRNAs (133a, 24, 29b, 132), and miRNAs promoting myocardial regeneration (199a and 590). We also show that ProtheraCytes have in vitro angiogenic activity, express surface markers of endothelial progenitor cells, and can differentiate in vitro into endothelial cells. After the in vitro characterization of multiple ProtheraCytes clinical batches, we established that measuring the concentration of VEGF provided the most practical, reliable, and consistent potency assay.

During the austral summer 2019/2020, three vertically pointing K-band Doppler profilers (Micro Rain Radar PRO, MRR-PRO) were deployed along a transect across the Sør Rondane Mountains, directly south of the scientific base Princess Elisabeth Antarctica. The MRR-PRO devices were placed at locations corresponding to different stages of the interaction between the complex terrain and the typical flow associated with precipitating systems. The radar measurements, alongside information from the ERA5 reanalysis and a set of high-resolution Weather Research and Forecasting (WRF) simulations, have been used to study the spatial variability in snowfall across the transect. Radar observations reveal differences in the frequency of occurrence of virga and surface precipitation above the transect. An analysis of the WRF outputs reveals the presence of a relatively dry layer above the radar locations, reaching a constant altitude of 3.5 km above mean sea level. Due to the complex terrain, the depth of the layer varies across the transect, affecting sublimation and the occurrence of virgae. Combined information from the ERA5 reanalysis, the WRF simulations, and ground-level measurements suggests that orographic lifting enhances precipitation above the highest mountain peaks. Finally, the analysis of the succession of virga and surface precipitation above the sites shows that, in most cases, they represent different stages of the same large-scale events. This study reveals the significant spatial variability in the occurrence of precipitation in a region of complex terrain, emphasizing the importance of collecting snowfall measurements in the mountainous regions of the Antarctic continent.

Abstract Primary cutaneous follicle centre lymphomas (PCFCLs) are cutaneous proliferation of centrocytes and centroblasts, with a generally indolent evolution. Secondary systemic spread of disease is a rare event, which significantly impairs prognosis. Recently published study by Zhou and al. proposed criteria aiming to predict such evolution at initial stage: (i) rearrangement of Bcl2, (ii) Ki67% index 30% Ki67% indexes and no mutations among the four proposed genes. These findings run contrary to these previously proposed criteria, highlighting the molecular heterogeneity of this rare disease.

Abstract Background Except in a few retrospective studies mainly including patients under chemotherapy, information regarding the impact of immunosuppressive therapy on the prognosis of patients admitted to the intensive care unit (ICU) for septic shock is scarce. Accordingly, the PACIFIC study aimed to asses if immunosuppressive therapy is associated with an increased mortality in patients admitted to the ICU for septic shock. Methods This was a retrospective epidemiological multicentre study. Eight high enroller centres in septic shock randomised controlled trials (RCTs) participated in the study. Patients in the “exposed” group were selected from the screen failure logs of seven recent RCTs and excluded because of immunosuppressive treatment. The “non-exposed” patients were those included in the placebo arm of the same RCTs. A multivariate logistic regression model was used to estimate the risk of death. Results Among the 433 patients enrolled, 103 were included in the “exposed” group and 330 in the “non-exposed” group. Reason for immunosuppressive therapy included organ transplantation (n = 45 [44%]) or systemic disease (n = 58 [56%]). ICU mortality rate was 24% in the “exposed” group and 25% in the “non-exposed” group (p = 0.9). Neither in univariate nor in multivariate analysis immunosuppressive therapy was associated with a higher ICU mortality (OR: 0.95; [95% CI 0.56–1.58]: p = 0.86 and 1.13 [95% CI 0.61–2.05]: p = 0.69, respectively) or 3-month mortality (OR: 1.13; [95% CI 0.69–1.82]: p = 0.62 and OR: 1.36 [95% CI 0.78–2.37]: p = 0.28, respectively). Conclusions In this study, long-term immunosuppressive therapy excluding chemotherapy was not associated with significantly higher or lower ICU and 3-month mortality in patients admitted to the ICU for septic shock.

This article focuses on the environmental impact of nuclear energy and addresses the following major environmental issues associated with nuclear power generation: ① controlling the radioactive discharge from nuclear installations under normal operation and evaluating their non-radioactive environmental impact (water withdrawals and non-radioactive discharges); ② long-term management of spent fuel and radioactive waste (radwaste), notably that disposed off in geological repositories; ③ prevention and mitigation of severe nuclear accidents and their radioactive releases and; ④ improving nuclear safety to restrict its environmental impact and to contribute toward the public acceptance of nuclear energy. Nuclear energy, with its very low emissions of green house gases, has a unique capacity to generate massive and on-demand dispatchable amounts of electricity. The annual effective radiation dose delivered to the public surrounding nuclear power plants under normal operation is negligible. Considerable efforts have been made to define sustainable management of high-level long-lived radwaste that is disposed in geological formations. The return of experience from severe nuclear accidents in the past has informed and propelled major improvements in several aspects of nuclear energy production—including reactor design and operational management as well as in the development of accident-management guidelines—and has proved to be highly valuable. The environmental risks in the event of a severe accident have been substantially reduced and protocols have been established to minimize the release of radioactive materials and avoid the large-scale evacuation of people in the event of a severe nuclear accident. Efforts must be continued to improve reactor safety and enhance the transparency of the industry and the authorities that support and control nuclear power to further reduce the environmental impact.

Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

Genomic analysis of three Neolithic individuals from Mentesh Tepe in Azerbaijan belonging to the beginnings of the Shomu-Shulaveri culture provides insight into the origin and population structure of the Shomu-Shulaveri community.

Abstract The Mediterranean basin and Northern Africa are projected to be among the most vulnerable areas to climate change. This research documents, analyzes, and synthesizes the projected changes in precipitation P, evapotranspiration E, net water supply from the atmosphere to the surface P–E, and surface soil moisture over these regions as simulated by 17 global climate models from the sixth exercise of the Coupled Model Intercomparison Project (CMIP6) under two Shared Socioeconomic Pathways, SSP2‐4.5, and SSP5‐8.5. It also explores the sensitivity of the results to the chosen climate scenario and model resolution and assesses how the projections have evolved from the fifth exercise (CMIP5). Models project a statistically robust drying over the entire Mediterranean and coastal North Africa. Over the Northern Mediterranean sector, a significant precipitation decrease reaching −0.4 ∓ 0.1 mm day−1 is projected during the 21st century under the SSP5‐8.5 scenario. Conversely, a significant increase in precipitation of +0.05 to 0.3 ∓ 0.1 mm day−1 is projected over South‐Eastern Sahara under the same scenario. Evapotranspiration and soil moisture exhibit decreasing trends over the Mediterranean basin and an increase over the Sahara for both SSPs, with a notable acceleration from the 2020s. As a result, P‐E is projected to decrease at a rate of about −0.3 mm day−1 under the high‐end scenario SSP5‐8.5 over the Mediterranean whilst no significant changes are expected over the Sahara due to evapotranspiration compensation effects. CMIP6 and CMIP5 models project qualitatively similar patterns of changes but CMIP6 models exhibit more intense changes over the Mediterranean basin and South‐Eastern Sahara, especially during winter.

Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy.

Weaning a critically-ill patient from the ventilator is a crucial step in global management. This manuscript details physiological changes induced by altered heart-lung interactions during the weaning process, illustrates the main mechanisms which could lead to weaning failure of cardiac origin, and discuss a tailored management based on the monitoring of changes in central hemodynamics during weaning. The transition from positive-pressure ventilation to spontaneous breathing results in abrupt hemodynamic and metabolic changes secondary to rapidly modified heart-lung interactions, sudden changes in cardiac loading conditions, and increased oxygen demand. These modifications may elicit an excessive burden on both the respiratory and cardiovascular systems, result in a rapid and marked increase of left ventricular filling pressure, and ultimately result in a weaning-induced pulmonary oedema (WIPO). The T-piece trial induces the greatest burden on respiratory and cardiocirculatory function when compared to spontaneous breathing trial using pressure support ventilation with positive or zero end-expiratory pressure. Since LV overload is the mainstay of WIPO, positive fluid balance and SBT-induced acute hypertension are the most frequently reported mechanisms of weaning failure of cardiac origin. Although the diagnosis of WIPO historically relied on an abrupt elevation of pulmonary artery occlusion pressure measured during right heart catheterization, it is nowadays commonly documented by echocardiography Doppler. This non-invasive approach is best suited for identifying high-risk patients, depicting the origin of WIPO, and tailoring individual management. Whether this strategy increases the success rate of weaning needs to be evaluated in a population at high risk of weaning failure of cardiac origin.

Abstract Background The AIRE operational project will evaluate the implementation of the routine Pulse Oximeter (PO) use in the integrated management of childhood illness (IMCI) strategy for children under-5 in primary health care centers (PHC) in West Africa. The introduction of PO should promote the accurate identification of hypoxemia (pulse blood oxygen saturation Sp02

Low-level easterly winds encircling Antarctica help drive coastal currents which modify transport of circumpolar deep water to ice shelves, and the formation and distribution of sea ice. Reanalysis datasets are especially important at high southern latitudes where observations are few. Here, we investigate the representation of the mean state and short-term variability of coastal easterlies in three recent reanalyses, ERA5, MERRA-2 and JRA-55. Reanalysed winds are compared with summertime marine near-surface wind observations from the Advanced Scatterometer (ASCAT) and surface and upper air measurements from coastal stations. Reanalysis coastal easterlies correlate highly with ASCAT (r= 0.91, 0.89 and 0.85 for ERA5, MERRA-2 and JRA-55, respectively) but notable wind speed biases are found close to the coastal margins, especially near complex orography and at high wind speeds. To characterise short-term variability, 12-hourly reanalysis and coastal station winds are composited using self-organising maps (SOMs), which cluster timesteps under similar synoptic and mesoscale influences. Reanalysis performance is sensitive to the flow configuration at stations near steep coastal slopes, where they fail to capture the magnitude of near-surface wind speed variability when synoptic forcing is weak and conditions favour katabatic forcing. ERA5 exhibits the best overall performance, has more realistic orography, and a more realistic jet structure and temperature profile. These results demonstrate the regime behaviour of Antarctica's coastal winds and indicate important features of the coastal winds which are not well characterised by reanalysis datasets.

Abstract Background Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness. Methods Twenty patients with CTEPH underwent pre-PEA and > 6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity. Results Mean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P

Goal: The purpose of this study is to develop a decision support framework to select critical success factors (CSFs) and benefits for the implementation of BIM in the public works sector. Design / Methodology / Approach: The research methodology integrates multiple fuzzy multicriteria decision making (MCDM) approaches to propose a composite framework of CSFs and benefits using qualitative and quantitative approaches, with the application of two semi-structured questionnaires with CSFs and benefits identified in previous studies, through a systematic literature review (SLR). Results: The study identified 42 CSFs and 31 benefits for the implementation of BIM for public works, and the relative importance of the identified factors and benefits was measured according to the four main BIM perspectives: legal, people, process, and technology. The result of the applied MCDMs showed the relationship between the factors and benefits of the four most influential BIM perspectives according to the proposed framework. The most influential CSFs and benefits were: BIM adoption requires individual and group motivation in the organization, Establishment of BIM and Lean construction standards, codes, rules, and regulations, Financial support from the government to establish BIM system, Availability of quality, schedule, and cost information during construction with BIM Accuracy and reliability of documents and data and BIM provides knowledge sharing among stakeholders, Workflow, productivity, and efficiency are affected by the transition to BIM, BIM technology reduces cost and time, Conflict detection, integration, coordination, and design validation, and Creating more efficient projects with stakeholder involvement, coordination, and oversight. Limitations of the investigation: The research sample consisted exclusively of Brazilian professionals and academics with experience in the implementation of BIM in public works. Practical implications: The proposed framework can be applied in implementation in public construction projects that aims to implement BIM considering the selection of critical success factors and benefits. Originality / Value: BIM methodology is widely used in the construction industry. However, there are few studies on CSFs and the benefits of BIM for the public sector, and there still lack of implementation frameworks proposal with empirical evidence.

Introduction: Integrated community care (ICC) is defined as an interweaving of health-care and social-care interventions deployed in spatial and relational proximity using an interdisciplinary and cross-sectoral approach. Consideration of territory scale and time scale are at the center of ICC practices. Its deployment in public health and social care networks (HSCN) can be complex due to their broad mandate, the complexity of their management, and accountability. Therefore, we aimed to describe ICC delivered by public HSCN to determine how, why, for whom, and in what circumstances ICC works and produces outcomes. Methods: A realist synthesis was conducted consisting of five steps consistent with realist synthesis standards (RAMESES projects) to produce configurations of Context – Mechanism – Outcomes (CMOc) and development of a middle-range explanatory theory of why and how the identified outcomes may have occurred. Results: In total, 26 studies were selected and used, as evidence, to support—either partially or fully—the production of CMOc based on the initial program theory. Nine unique CMO configurations were identified based on the data analyses and team discussion. ICC middle-range theory is informed by the CMO configurations identified. Discussion: This realist synthesis allowed us to identify the central mechanisms of ICC delivered by public HSCN and to produce a middle range theory. ICC is based on a specific philosophy and deployed by a professional agency oriented toward a community agency within a local system of interdisciplinary and cross-sectoral action. Conclusion: Our middle-range theory will provide a solid analytical framework as a foundation for ICC implementation and future research. Résumé Introduction: Les interventions en santé et services sociaux intégrées en proximité des communautés (IIPC) sont définies comme une imbrication d’interventions de soins de santé et de services sociaux à l’échelle du territoire et considérant la temporalité, déployées dans une proximité spatiale et relationnelle au moyen d’une approche interdisciplinaire et intersectorielle. Son déploiement dans les réseaux publics de santé et de soins sociaux (RSSS) peut s’avérer complexe en raison de l’étendue de leur mandat, de la complexité de leur gestion et de leur responsabilité. C’est pourquoi nous avons cherché à décrire les IIPC dispensées par les RSSS publics afin de déterminer comment, pourquoi, pour qui et dans quelles circonstances les IIPC fonctionnent et produisent des résultats. Méthodes utilisées: Une synthèse réaliste a été réalisée en cinq étapes conformes aux normes de synthèse réaliste (projet RAMESES) afin de produire des configurations Contexte – Mécanisme – Effets (CMOc) et de développer une théorie explicative de moyenne portée sur le pourquoi et le comment des résultats identifiés. Résultats: Au total, 26 études ont été sélectionnées et utilisées comme preuves pour étayer – partiellement ou totalement – la production de CMOc sur la base de la théorie initiale de programme. Neuf configurations uniques CMO ont été identifiées sur la base des analyses de données et des discussions de l’équipe. La théorie de moyenne portée des IIPC s’appuie sur les configurations CMO identifiées. Discussion: Cette synthèse réaliste nous a permis d’identifier les mécanismes centraux des IIPC déployées par les RSSS publics et de produire une théorie de moyenne portée. Les IIPC sont fondées sur une philosophie et le développement d’une capacité d’agir professionnelle mise en action vers le renforcement de la capacité d’agir de la communauté au sein d’un système local d’action interdisciplinaire et intersectoriel. Conclusion: L’utilisation de notre théorie de moyenne portée pour la mise en œuvre d’IIPC fournira un cadre analytique solide comme base pour des implantations ou des recherches futures. Mots clés: Interventions en santé et services sociaux intégrées en proximité des communautés; soins de santé; soins sociaux; services publics; proximité; territoire