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Climate change projections are often given as equally weighted averages across ensembles of climate models, despite the fact that the sampling of the underlying ensembles is unclear. We show that a hierarchical clustering of a metric of spatial and temporal variations of either surface temperature or precipitation in control simulations can capture many model relationships across different ensembles. Strong similarities are seen between models developed at the same institution, between models sharing versions of the same atmospheric component, and between successive versions of the same model. A perturbed parameter ensemble of a model appears separate from other structurally different models. The results provide insight into intermodel relationships, into how models evolve through successive generations, and suggest that assuming model independence in such ensembles of opportunity is not justified. Key Points Models by the same institution behave similarly Structural model uncertainty is important Model development resembles an evolutionary process

Aluminum compounds are the most widely used adjuvants in veterinary and human vaccines. Despite almost a century of use and substantial advances made in recent decades about their fate and biological effects, the exact mechanism of their action has been continuously debated, from the initial “depot-theory” to the direct immune system stimulation, and remains elusive. Here we investigated the early in vitro response of primary human PBMCs obtained from healthy individuals to aluminum oxyhydroxide (the most commonly used adjuvant) and a whole vaccine, in terms of internalization, conventional and non-conventional autophagy pathways, inflammation, ROS production, and mitochondrial metabolism. During the first four hours of contact, aluminum oxyhydroxide particles, with or without adsorbed vaccine antigen, (1) were quickly recognized and internalized by immune cells; (2) increased and balanced two cellular clearance mechanisms, i.e. canonical autophagy and LC3-associated phagocytosis; (3) induced an inflammatory response with TNF-α production as an early event; (4) and altered mitochondrial metabolism as assessed by both decreased maximal oxygen consumption and reduced mitochondrial reserve, thus potentially limiting further adaptation to other energetic requests. Further studies should consider a multisystemic approach of the cellular adjuvant mechanism involving interconnections between clearance mechanism, inflammatory response and mitochondrial respiration.

The aim of the PRECOG study was to evaluate if the use of the sFlt-1/PlGF ratio in patients hospitalized for suspected preeclampsia before 35 weeks could improve patient management and reduce the length of hospitalization. A prospective randomized multicenter interventional open-label study in a hospital population with 2 parallel groups with or without taking into account the sFlt-1/PlGF ratio for the management of patients admitted for suspected pre-eclampsia. 80 patients were included in the study. Characteristics of patients were equally distributed among randomization groups. There was no difference in the primary outcome between the two groups. Hospitalization for more than 24 h was 75% in the group reveal versus 80% in the group conceal (Relative Risk p  = 0.59). Groups did not differ in hospitalization duration for different cut-off values such. When stratifying by ratio value, among those with a ratio < 38, 37% were discharged home < 24 h in the conceal group and 47% in the reveal group. There was no difference in the secondary outcomes between the two groups. In this randomized controlled trial in women hospitalized for suspected of preeclampsia, the use of the sFlt-1/PlGF ratio at was not associated with a benefit in terms of duration of hospitalization or in maternal and neonatal outcomes.

Statistical models of the relationship between precipitation and topography are key elements for the spatial interpolation of rain-gauge measurements in high-mountain regions. This study investigates several extensions of the classical precipitation–height model in a direct comparison and within two popular interpolation frameworks, namely linear regression and kriging with external drift. The models studied include predictors of topographic height and slope at several spatial scales, a stratification by types of a circulation classification, and a predictor for wind-aligned topographic gradients. The benefit of the modeling components is investigated for the interpolation of seasonal mean and daily precipitation using leave-one-out cross-validation. The study domain is a north–south cross section of the European Alps (154 km × 187 km) that is inclined towards dense rain-gauge measurements (approx. 440 stations, 1971–2008). The significance of the topographic predictors was found to strongly depend on the interpolation framework. In linear regression, predictors of slope and at multiple scales reduce interpolation errors substantially. But with as many as nine predictors, the resulting interpolation still poorly replicates the across-ridge variation of climatological mean precipitation. Kriging with external drift (KED) leads to much smaller interpolation errors than linear regression, but this is achieved with a single predictor (local topographic height), whereas the incorporation of more extended predictor sets brings only marginal further improvement. Furthermore, the stratification by circulation types and the wind-aligned gradient predictor do not improve over the single predictor KED model. As for daily precipitation, interpolation accuracy improves considerably with KED and the use of a single predictor field (the distribution of seasonal mean precipitation) as compared to ordinary kriging (i.e., without any predictor). Nonetheless, information from circulation types did not improve interpolation accuracy. Our results confirm that the consideration of topography effects is important for spatial interpolation of precipitation in high-mountain regions. But a single predictor may be sufficient and taking appropriate account of the spatial autocorrelation (by kriging) can be more effective than the development of elaborate predictor sets within a regression model. Our results also question a popular practice of using linear regression for predictor selection in spatial interpolation; however they support the common practice of using a climatological mean field as a background in the interpolation of daily precipitation.

Submarine landslides can generate sediment-laden flows whose scale is impressive. Individual flow deposits have been mapped that extend for 1,500 km offshore from northwest Africa 1 , 2 , 3 , 4 , 5 , 6 , 7 . These are the longest run-out sediment density flow deposits yet documented on Earth. This contribution analyses one of these deposits, which contains ten times the mass of sediment transported annually by all of the world’s rivers 8 . Understanding how this type of submarine flow evolves is a significant problem, because they are extremely difficult to monitor directly 9 . Previous work has shown how progressive disintegration of landslide blocks can generate debris flow, the deposit of which extends downslope from the original landslide 10 , 11 , 12 , 13 . We provide evidence that submarine flows can produce giant debris flow deposits that start several hundred kilometres from the original landslide, encased within deposits of a more dilute flow type called turbidity current. Very little sediment was deposited across the intervening large expanse of sea floor, where the flow was locally very erosive. Sediment deposition was finally triggered by a remarkably small but abrupt decrease in sea-floor gradient from 0.05° to 0.01°. This debris flow was probably generated by flow transformation from the decelerating turbidity current. The alternative is that non-channelized debris flow left almost no trace of its passage across one hundred kilometres of flat (0.2° to 0.05°) sea floor. Our work shows that initially well-mixed and highly erosive submarine flows can produce extensive debris flow deposits beyond subtle slope breaks located far out in the deep ocean.

Purpose Short-segment minimally invasive percutaneous spinal osteosynthesis has now become one of the treatments of choice to treat thoracolumbar fractures. The question of implant removal once the fracture has healed is still a matter of debate since this procedure can be associated with loss of sagittal correction. Therefore, we analyzed risk factors for kyphosis recurrence after spinal implants removal in patients treated with short-segment minimally invasive percutaneous spinal instrumentation for a thoracolumbar fracture. Methods A total of 32 patients who underwent implant removal in percutaneous osteosynthesis for post-traumatic thoracolumbar fracture were enrolled in our study. Patient’s medical record, operative report and imaging examinations carried out at the trauma and during the follow-up were analyzed. Results Every patient experienced fracture union. Vertebral kyphotic angle (VKA) and Cobb angle (CA) improved significantly after stabilization surgery. VKA, CA, upper disk kyphotic angle (UDKA) and lower disk kyphotic angle (LDKA) significantly gradually decreased during follow-up. Traumatic disk injury ( p : 0.001), younger age ( p : 0.01), canal compromise ( p : 0.04) and importance of surgical correction ( p  < 0.001) were significantly associated with kyphosis recurrence after implant removal. Anterior body augmentation did not affect loss of correction (CA and VKA) during the follow-up period ( p : 0.57). Conclusion Despite correction of the fracture after stabilization, we observed a progressive loss of correction over time appearing even before implant removal. Particular attention should be paid to post-traumatic disk damage or canal invasion, to young patients and to surgical overcorrection of the traumatic kyphosis.

Huge landslides, mobilizing hundreds to thousands of km3 of sediment and rock are ubiquitous in submarine settings ranging from the steepest volcanic island slopes to the gentlest muddy slopes of submarine deltas. Here, we summarize current knowledge of such landslides and the problems of assessing their hazard potential. The major hazards related to submarine landslides include destruction of seabed infrastructure, collapse of coastal areas into the sea and landslide-generated tsunamis. Most submarine slopes are inherently stable. Elevated pore pressures (leading to decreased frictional resistance to sliding) and specific weak layers within stratified sequences appear to be the key factors influencing landslide occurrence. Elevated pore pressures can result from normal depositional processes or from transient processes such as earthquake shaking; historical evidence suggests that the majority of large submarine landslides are triggered by earthquakes. Because of their tsunamigenic potential, ocean-island flank collapses and rockslides in fjords have been identified as the most dangerous of all landslide related hazards. Published models of ocean-island landslides mainly examine 'worst-case scenarios' that have a low probability of occurrence. Areas prone to submarine landsliding are relatively easy to identify, but we are still some way from being able to forecast individual events with precision. Monitoring of critical areas where landslides might be imminent and modelling landslide consequences so that appropriate mitigation strategies can be developed would appear to be areas where advances on current practice are possible.

Gastrointestinal symptoms are frequent in acute adrenal insufficiency. Although digestive symptoms can significantly reduce quality of life, they are rarely described in patients with treated chronic adrenal insufficiency (CAI). We aimed to characterize digestive symptoms in CAI patients. We used the section pertaining functional bowel disorders of the Rome IV questionnaire. A questionnaire was published on the website of the non-profit patient association “Adrenals” (NPPA of CAI patients) for five months. Information on demographics, characteristics of adrenal insufficiency, digestive symptoms and quality of life was collected. The relatives of CAI patients served as a control group. We analyzed responses of 33 control subjects and 119 patients (68 primary adrenal insufficiency (PAI), 30 secondary adrenal insufficiency (SAI) and 21 congenital adrenal hyperplasia (CAH)). Abdominal pain at least once a week over the past 3 months was reported by 40%, 47% and 33% of patients with PAI, SAI and CAH respectively versus 15% for the controls ( p  = 0.01). Symptoms were consistent with the Rome IV criteria for irritable bowel syndrome in 27%, 33% and 33% of patients respectively versus 6% for the controls ( p  < 0.0001). Quality of life was described as poor or very poor in 35%, 57% and 24% of patients respectively versus 5% for the controls ( p  < 0.0001). In conclusion, digestive symptoms are frequent and incapacitating in CAI patients and similar to symptoms of irritable bowel syndrome in 30% of CAI patients. Assessment and management of digestive symptoms should be considered a priority for physicians treating patients with CAI.

Nous rapportons les attitudes et pratiques des soignants en Afrique francophone concernant l’annonce du statut VIH aux adolescents, et les témoignages de jeunes vivant avec le VIH (jvVIH). Lors d’un atelier de trois jours à Abidjan, Côte d’Ivoire, en novembre 2016, les soignants (médecins, psychologues, travailleurs sociaux) de 19 sites de prise en charge pédiatrique du VIH ont partagé leurs pratiques et difficultés et 4 jvVIH leur vécu de l’annonce. Au total, 35 participants de 8 pays d’Afrique de l’Ouest/centrale (Bénin, Burkina Faso, Côte d’Ivoire, Cameroun, Mali, République démocratique du Congo, Sénégal, Togo) ont contribué : 14 médecins, 8 psychologues, 6 conseillers, 3 travailleurs sociaux. L’expérience des centres était variable, mais l’âge à l’annonce restait tardif : 34 % des 1 296 adolescents âgés entre 10 et 12 ans connaissaient leur statut. L’âge médian à l’annonce était de 13 ans (étendue : 11-15 ans). La pratique de l’annonce s’avérait complexe, en raison de multiples facteurs (crainte des parents de la rupture du secret, manque de communication entre professionnels). L’annonce individuelle était la pratique majoritairement adoptée. Quatre centres pratiquaient une annonce en séances de groupe pour faciliter le soutien en miroir, et un avait recours à l’appui de pairs-adolescents. Les jvVIH ont plaidé pour une annonce plus précoce, dès 10 ans. En Afrique de l’Ouest/centrale francophone, le processus de l’annonce reste complexe pour parents et soignants, et l’annonce trop tardive. L’élaboration d’un guide de bonnes pratiques de l’annonce du VIH, adapté aux contextes socio-culturels devrait permettre d’améliorer ce processus.

IntroductionThis pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC).Patients and methodsPatients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up.ResultsEleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98–13.94, SD 3.37], 8.63 cm3 [1.98–46.64; SD 14.83] and 37.90 cm3 [8.07–127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients.ConclusionThis pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance.Trial registrationClinicalTrials.gov NCT02587247Registered 27 October 2015