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ABSTRACT Background Methods Results Conclusion While some labor interventions are essential in preventing maternal and neonatal morbidity, there is little evidence to support systematic early augmentation of labor (EAL). Our objective was to assess the association between EAL and cesarean delivery rate, postpartum hemorrhage and adverse neonatal outcomes.Population‐based study using data from the 2016 French Perinatal Survey. Women with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. “EAL” was defined by artificial rupture of the membranes (AROM) and/or oxytocin within 1 h of admission and/or duration between interventions of less than 1 h. Women without EAL were women without labor augmentation or without EAL. The primary endpoint, cesarean delivery and the secondary endpoints were compared between women with and without EAL using univariate analysis. A multivariable logistic regression was adjusted on the suspected confounders and a propensity score approach was then performed.Among the 7196 women included, 1524 (21.2%) had EAL. Cesarean delivery rates were significantly higher in the EAL group compared with the no EAL group, 8.40% versus 6.15% (p < 0.01). EAL was associated with cesarean delivery in the multivariable analysis aOR 1.45 95% CI [1.15–1.82] and in the cohort matched on the propensity score, OR 1.56 [1.17–2.07]. EAL was not associated with severe postpartum hemorrhage, low 5‐min Apgar score, low neonatal cord pH or transfer to NICU.EAL is frequent, involving one in five spontaneous laboring women in France. This practice is associated with an increased cesarean delivery risk. [ABSTRACT FROM AUTHOR]

Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first‐line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug‐resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone–implant interface. [ABSTRACT FROM AUTHOR]

Summary: This article presents the development of a new wind turbine simulation software to study wake flow physics. To this end, the design and development of waLBerla‐wind, a new simulator based on the lattice‐Boltzmann method that is known for its excellent performance and scaling properties, will be presented. Here it will be used for large eddy simulations (LES) coupled with actuator wind turbine models. Due to its modular software design, waLBerla‐wind is flexible and extensible with regard to turbine configurations. Additionally it is performance portable across different hardware architectures, another critical design goal. The new solver is validated by presenting force distributions and velocity profiles and comparing them with experimental data and a vortex solver. Furthermore, waLBerla‐wind's performance is compared to a theoretical peak performance, and analyzed with weak and strong scaling benchmarks on CPU and GPU systems. This analysis demonstrates the suitability for large‐scale applications and future cost‐effective full wind farm simulations. [ABSTRACT FROM AUTHOR]

Several factors influence whether an organism remains in its local habitat. Parasites can, for example, influence host movement by impacting their behavior, physiology, and morphology. In rivers, fish that swim efficiently against the current are able to maintain their position without being displaced downstream, a behavior referred to as positive rheotaxis. We hypothesized that both the presence and number of ectoparasites on a host would affect the ability of fish to avoid downstream displacement and thus prevent them from remaining in their habitat. We used the guppy‐Gyrodactylus host‐ectoparasite model to test whether parasite presence and parasite load had an effect on fish rheotaxis. We quantified rheotaxis of sham‐infected and parasite‐infected fish in a circular flow tank in the laboratory prior to infection and 5–6 days postinfection. Both parasite‐infected and sham‐infected individuals expressed similar levels of positive rheotaxis prior to infection and after infection. However, with increasing parasite numbers, guppies covered less distance in the upstream direction and spent more time in slower flow zones. These results suggest that higher numbers of Gyrodactylus ectoparasites negatively influence rheotactic movements. Further research is needed to understand the ecological and evolutionary implications of this ectoparasite on fish movement. [ABSTRACT FROM AUTHOR]

This paper presents a lifting‐line implementation in the framework of a Lagrangian vortex particle method (LL‐VP). The novelty of the present implementation lies in the fluid particles properties definition and in the particles shedding process. In spite of mimicking a panel method, the LL‐VP needs some peculiar treatments described in the paper. The present implementation converges rapidly and efficiently during the shedding sub‐iteration process. This LL‐VP method shows good accuracy, even with moderate numbers of sections. Compared to its panel or vortex filaments counterparts, more frequently encountered in the literature, the present implementation inherently accounts for the diffusion term of the Navier‐Stokes equations, possibly with a turbulent viscosity model. Additionally, the present implementation can also account for more complex onset flows: upstream ambient turbulence and upstream turbine wakes. After validation on an analytical elliptic wing configuration, the model is tested on the Mexnext‐III wind turbine application, for three reduced velocities. Accurate results are obtained both on the analytical elliptic wing and on the New MEXICO rotor cases in comparison with other similar numerical models. A focus is made on the Mexnext‐III wake analysis. The numerical wake obtained with the present LL‐VP is close to other numerical and experimental results. Finally, a last configuration with three tidal turbines in interaction is considered based on an experimental campaign carried out at the IFREMER wave and current flume tank. Enhanced turbine‐wake interactions are highlighted, with favourable comparisons with the experiment. Hence, such turbine interactions in a farm are accessible with this LL‐VP implementation, be it wind or tidal energy field. [ABSTRACT FROM AUTHOR]

B cells present in human cutaneous melanoma have been associated with protective or detrimental effects on disease progression according to their phenotype. By using the RET model of spontaneous melanoma and adoptive transfer of B16 melanoma cells, we show that immature and follicular B2 (B2‐FO) cells exert a protective effect on melanoma progression by promoting the generation of effector memory T cells and limiting the recruitment of polymorphonuclear myeloid‐derived suppressor cells. Unfortunately, this beneficial effect progressively wanes as a consequence of enhanced expression of the IL4‐induced gene 1 (IL4I1) enzyme by immature B cells and B2‐FO cells. Endogenous IL4I1 selectively decreases CXCR5 expression in splenic immature B cells, subverting their trafficking to primary tumors and enhancing the production of IL‐10 by B2 cells, thereby promoting an immunosuppressive microenvironment. Accordingly, B2 cells from RET IL4I1KO mice more efficiently controlled B16 melanoma growth than B2 cells from IL4I1‐competent RET mice. Collectively, immature B cells and B2‐FO cells are key actors in the control of melanoma growth, but their mobility and functions are differently impaired by IL4I1 overexpression during melanoma progression. Thus, our present data strongly urge us to associate an IL4I1 antagonist with current immunotherapy to improve the treatment of metastatic melanoma. [ABSTRACT FROM AUTHOR]

The emergence of SARS‐CoV‐2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID‐19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67–86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic. [ABSTRACT FROM AUTHOR]

Background: Predicting progression of myxomatous mitral valve disease (MMVD) in dogs can be challenging. Hypothesis/Objectives: The mitral regurgitation severity index (MRSI) will predict time to congestive heart failure (CHF) and all‐cause death in dogs with MMVD. Animals: Eight hundred sixty‐nine client‐owned dogs. Methods: Retrospective study pooling data from 4 previous samples including dogs with MMVD stage B2 or C. MRSI was calculated as: (heart rate [HR]/120) × left atrium‐to‐aorta ratio (LA:Ao) × (age in years/10) × 100. Alternative MRSI formulas substituting radiographic measures of left atrial size were also calculated. Cox proportional hazard modeling and time‐dependent receiver‐operator characteristic curves quantified prognostic performance. Results: For Stage B2 pooled samples, MRSI > 156 was predictive of time to CHF (median 407 vs 1404 days; area under the curve [AUC] 0.68; hazard ratio 3.02 [95% CI 1.9‐4.9]; P <.001). MRSI > 173 was predictive of all‐cause death (median survival 868 vs 1843 days; AUC 0.64; hazard ratio 4.26 [95% CI 2.4‐7.5]; P <.001). MRSI showed superior predictive value compared to the individual variables of HR, LA:Ao, and age. Variations of the MRSI equation substituting radiographic vertebral left atrial size for LA:Ao were also significantly predictive of outcome in stage B2. MRSI was not consistently predictive of outcome in Stage C. Conclusions and Clinical Importance: MRSI was predictive of outcome (onset of CHF and all‐cause death) in MMVD Stage B2, demonstrating utility as a useful prognostic tool. Echocardiographic LA:Ao can be effectively replaced by radiographically determined LA size in the MRSI formula. [ABSTRACT FROM AUTHOR]

Terrestrial ecosystems are shaped by interacting top‐down and bottom‐up processes, with the magnitude of top‐down control by large carnivores largely depending on environmental productivity. While carnivore‐induced numerical effects on ungulate prey populations have been demonstrated in large, relatively undisturbed ecosystems, whether large carnivores can play a similar role in more human‐dominated systems is a clear knowledge gap. As humans influence both predator and prey in a variety of ways, the ecological impacts of large carnivores can be largely modified. We quantified the interactive effects of human activities and large carnivore presence on red deer (Cervus elaphus) population density and how their impacts interacted and varied with environmental productivity.Data on red deer density were collected based on a literature survey encompassing 492 study sites across 28 European countries. Variation in density across study sites was analysed using a generalized additive model in which productivity, carnivore presence (grey wolf, European lynx, Brown bear), human activities (hunting, intensity of human land‐use activity), site protection status and climatic variables served as predictors.The results showed that a reduction in deer density only occurred when wolf, lynx and bear co‐occurred within the same site. In the absence of large carnivores, red deer density varied along a productivity gradient without a clear pattern. Although a linear relationship with productivity in the presence of all three large carnivore species was found, this was not statistically significant. Moreover, hunting by humans had a stronger effect than the presence of all large carnivores in reducing red deer density and red deer density increased with increasing intensity of human land use, with stronger large carnivore effects (all three carnivore species present) at sites with low human land‐use activities.Synthesis and applications. This study provides evidence for the dominant role played by humans (i.e. hunting, land‐use activities) relative to large carnivores in reducing red deer density across European human‐dominated landscapes. These findings suggest that when we would like large carnivores to exert numeric effects, we should focus on minimizing human impacts to allow the ecological impacts of large carnivores on ecosystem functioning. [ABSTRACT FROM AUTHOR]

Background: Shared decision‐making is an important component of a patient‐centered healthcare system. We assessed the prevalence of parturients with preferences for their labor and childbirth, expressed verbally in the birthing room or as a written birth plan, and studied maternal, obstetric, and organizational factors associated with their expression. Methods: Data came from the 2016 National Perinatal Survey, a cross‐sectional nationwide population‐based survey conducted in France. Preferences for labor and childbirth were studied in three categories: expressed verbally, in writing (birth plan), or unexpressed or nonexistent. Analyses used multinomial multilevel logistic regression. Results: The analysis included 11,633 parturients: 3.7% had written a birth plan, 17.3% expressed their preferences verbally, and 79.0% either did not have or did not express any preferences. Compared with the latter group, written or verbal preferences were both significantly associated with prenatal care by independent midwives (respectively, adjusted odds ratio (aOR) 2.19; 95% confidence interval (CI), [1.59–3.03], and aOR 1.43; 95% CI [1.19–1.71]) and with attendance at childbirth education classes (respectively, aOR 4.99; 95% CI [3.49–7.15], and aOR 2.27; 95% CI [1.98–2.62]). As years in traditional schooling increased, so did its association with preferences. Conversely, parturients from African countries were significantly less likely than French mothers to express preferences. A written birth plan was also associated with characteristics of maternity unit organization. Conclusion: Only one in five parturients reported having expressed preferences for labor and childbirth to healthcare professionals in the birthing room. This expression of preferences was associated with maternal characteristics and the organization of care. [ABSTRACT FROM AUTHOR]

The constant selection and propagation of multi‐resistant Plasmodium sp. parasites require the identification of new antimalarial candidates involved in as‐yet untargeted metabolic pathways. Subtilisin‐like protease 1 (SUB1) belongs to a new generation of drug targets because it plays a crucial role during egress of the parasite from infected host cells at different stages of its life cycle. SUB1 is characterized by an unusual pro‐region that tightly interacts with its cognate catalytic domain, thus precluding 3D structural analysis of enzyme–inhibitor complexes. In the present study, to overcome this limitation, stringent ionic conditions and controlled proteolysis of recombinant full‐length P. vivax SUB1 were used to obtain crystals of an active and stable catalytic domain (PvS1Cat) without a pro‐region. High‐resolution 3D structures of PvS1Cat, alone and in complex with an α‐ketoamide substrate‐derived inhibitor (MAM‐117), showed that, as expected, the catalytic serine of SUB1 formed a covalent bond with the α‐keto group of the inhibitor. A network of hydrogen bonds and hydrophobic interactions stabilized the complex, including at the P1′ and P2′ positions of the inhibitor, although P′ residues are usually less important in defining the substrate specificity of subtilisins. Moreover, when associated with a substrate‐derived peptidomimetic inhibitor, the catalytic groove of SUB1 underwent significant structural changes, particularly in its S4 pocket. These findings pave the way for future strategies for the design of optimized SUB1‐specific inhibitors that may define a novel class of antimalarial candidates. [ABSTRACT FROM AUTHOR]

French school policies also promote the training of school staff in anaphylaxis recognition and appropriate use of AAI. Our objective was to assess the implementation of stock AAI and school staff training in anaphylaxis recognition and management and to assess the barriers to implementation. In 2019, school staff training regarding anaphylaxis recognition and AAI use was performed in 53/221 (24%) secondary schools with stock AAI compared to 256/334 (77%) in 2023 ( I p i < 10 SP -3 sp ) with an increase of 53% (95% CI: 46-60). In conclusion, our findings highlight the key role of school nurses regarding stock AAI implementation and school staff training. [Extracted from the article]

This study presents the results of the classification of diffuse reflectance (DR) spectra and multiexcitation autofluorescence (AF) spectra that were collected in vivo from precancerous and benign skin lesions at three different source detector separation (SDS) values. Spectra processing pipeline consisted of dimensionality reduction, which was performed using principal component analysis (PCA), followed by classification step using such methods as support vector machine (SVM), multilayered perceptron (MLP), linear discriminant analysis (LDA), and random forest (RF). In order to increase the efficiency of lesion classification, several data fusion methods were applied to the classification results: majority voting, stacking, and manual optimization of weights. The results of the study showed that in most of cases the use of data fusion methods increased the average multiclass classification accuracy from 2% up to 4%. The highest accuracy of multiclass classification was obtained using the manual optimization of weights and reached 94.41%. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to identify factors associated with episiotomy practice in France, in particular, characteristics of the maternity units and regions of delivery. Material and methods: We performed a national cross‐sectional population‐based study in all French maternity units in 2016 including 9284 women with vaginal delivery. Our outcome was the performance of an episiotomy. After stratification for parity, associations of episiotomy practice with individual and organizational characteristics and the region of delivery were estimated with multilevel logistic regression models. The variability in maternity unit episiotomy rates explained by the characteristics studied was estimated by the proportional change in variance. Results: A total of 19.9% of the women had an episiotomy. The principal factors associated with episiotomy practice were maternal and obstetric and delivery in a maternity unit with <2000 annual deliveries. After adjusting for individual, obstetric and organizational characteristics, the practice of episiotomy was strongly associated with women's region of delivery. Additionally, women's individual characteristics did not explain the significant variability in episiotomy rates between maternity units (P < 0.001) but maternity unit characteristics partly did (proportion of variance explained: 7.2% for primiparas and 13.6% for multiparas) and regional differences still more (18% and 30.7%, respectively). Conclusions: Episiotomy practices in France in 2016 varied strongly between maternity units, largely due to regional differences. Targeted actions by the regional perinatal care networks may reduce the national episiotomy rate and standardize practices. [ABSTRACT FROM AUTHOR]

Introduction: Research on maternal prepregnancy weight suggests adiposity is associated with dysfunctional labor, but knowledge about how gestational weight gain (GWG) affects labor is sparse. Our objective was to evaluate associations between GWG adequacy and intrapartum obstetric interventions (oxytocin administration; cesarean section) necessitated by labor dysfunction. Material and methods: Using national, population‐based French National Perinatal Survey 2016 data, we included term cephalic singleton pregnancies involving trial of labor (n = 9724). For the intrapartum oxytocin administration analysis, we included only women with spontaneous labor (n = 7352). GWG was calculated as the difference between end of pregnancy and prepregnancy weight (both self‐reported) and categorized as insufficient, adequate (reference group), or excessive by prepregnancy body mass index (BMI; underweight <18.5, normal weight 18.5–24.9, overweight 25–29.9, obese ≥30 kg/m2) using the 2009 Institute of Medicine thresholds. Multilevel generalized estimating equation logistic regression models, unadjusted and adjusted for a priori confounders, evaluated intervention‐GWG adequacy associations within BMI categories (under/normal weight combined), stratified by parity (primiparas; multiparas). Results: GWG adequacy was associated with oxytocin use among under/normal weight women (primiparas: insufficient 57.3%, adequate 60.8%, excessive 65.0%, p = 0.014; multiparas: insufficient 27.2%, adequate 29.1%, excessive 36.2%, p < 0.001) and overweight primiparas (insufficient 56.0%, adequate 58.7%, excessive 72.5%, p = 0.002). In unadjusted and adjusted models, trends of increased odds of oxytocin administration among women with excessive GWG were found regardless of parity and prepregnancy BMI. Similarly, among under/normal weight women, GWG adequacy was associated with intrapartum cesarean section (primiparas: insufficient 10.7%, adequate 12.7%, excessive 15.3%, p = 0.014; multiparas: insufficient 3.1%, adequate 3.5%, excessive 6.3%, p < 0.001) with increased cesarean section among multiparas with excessive GWG persisting in adjusted models (adjusted odds ratio 1.9, 95% confidence interval 1.3–2.7). However, intrapartum cesarean section was reduced among multiparas with overweight and obese prepregnancy BMI and excessive GWG. Conclusions: Excessive GWG was associated with intrapartum oxytocin administration, regardless of parity or prepregnancy BMI, and cesarean section among women with under/normal weight prepregnancy BMI, providing evidence for benefits of healthy GWG for normal labor progression. Additional research is needed to verify our findings and understand differences by BMI. [ABSTRACT FROM AUTHOR]

Field analogues illustrating the early stage of deformation of shortening structures in salt‐bearing orogenic fold‐and‐thrust belts are not yet well illustrated in literature. The relatively young Messinian salt of the Algerian basin could represent a good case example of such systems. The Algerian Basin is a deep‐water Miocene back‐arc basin including a layer of mobile Messinian evaporites up to 2 km thick. The Messinian salt was deposited in an already inverted basin, after its extensive stage. Its inversion initiated in the Tortonian, with a N‐NW shortening induced by the north‐westward motion of the African plate. In this study, we use new 2D multichannel seismic data to identify, classify and map salt structures throughout the central Algerian Basin and re‐assess its structural style. We interpret contractional salt tectonic structures, such as buckle folds, squeezed diapirs and related salt sheets as evidence of regional thick‐skinned shortening episodes. We conclude that horizontal displacement loading has driven salt deformation within the basin since its deposition. We also show spatial variations in the structural style of the central Algerian Basin, both along‐ and down‐dip. We demonstrate that the initial shortening‐related salt deformation in the late Messinian was focussed along the Algerian margin and later shifted outward toward the Balearic margin in the Plio‐Quaternary. The shifting of the deformation front is interpreted to be a result of the thickening and strengthening of the overburden. The second peak of deformation may have reactivated faults along the Emile‐Baudot escarpment with thick‐skinned deformation. We also observe a variation in the intensity of the salt deformation along the margin from SW to NE, which may be due to variable tectonic loading applied along the Algerian margin or the pre‐shortening distribution of salt. [ABSTRACT FROM AUTHOR]

Breastfeeding (BF) initiation rates in French maternity units are among the lowest in Europe. After increasing for several years, they decreased between 2010 and 2016, although several maternal characteristics known to be positively associated with BF in France were more frequent. We aimed to (1) quantify adjusted trends in BF initiation rates between 2010 and 2016; (2) examine associations between BF initiation rates and newborn, maternal, maternity unit, and department‐level characteristics. Using data from the 2010 (n = 12,224) and 2016 (n = 11,089) French National Perinatal Surveys, we analysed BF initiation (exclusive, mixed, and any) through a succession of six mixed‐effect multinomial regression models, progressively adding adjustment covariates. Adjusted exclusive and any BF initiation rates decreased by 9.6 and 4.5 points, respectively, versus by 7.7 and 1.8 points, respectively, in the crude analysis. In both years, adjusted exclusive and any BF initiation rates were lowest in the following categories of mothers: low education level, single, high body mass index and multiple or premature births. Exclusive BF initiation decreased most in primiparous mothers, those with the lowest household income, mothers that had a vaginal delivery, women born in an African country and those who delivered in a maternity unit without Baby‐Friendly Hospital Initiative designation. The 2010–2016 decrease in BF initiation rates in France cannot be explained by changes in mothers' characteristics; quite the opposite, adjustment increased its magnitude. Additional efforts should be put in place to understand why this decrease is particularly sharp in some subgroups of mothers. Key points: While some maternal characteristics previously known to be positively associated with breastfeeding (BF) in France were more frequent in 2016 than 2010, any BF initiation rate in maternity units in France decreased by 2 points (from 68.7% to 66.7%), and exclusive BF by 8 points (from 60.3% to 52.2%). Even greater decreases (4.5 and 9.6 points, respectively) were observed after adjusting for the characteristics of mothers, newborns, maternity units, and departments.Between 2010 and 2016, the largest decreases in adjusted exclusive BF initiation rates were observed in primiparous mothers, those with the lowest household income, mothers that had a vaginal delivery, women born in an African country and those who delivered in a maternity unit without Baby‐Friendly Hospital Initiative designation. [ABSTRACT FROM AUTHOR]

Mitochondrial complex V plays an important role in oxidative phosphorylation by catalyzing the generation of ATP. Most complex V subunits are nuclear encoded and not yet associated with recognized Mendelian disorders. Using exome sequencing, we identified a rare homozygous splice variant (c.87+3A>G) in ATP5PO, the complex V subunit which encodes the oligomycin sensitivity conferring protein, in three individuals from two unrelated families, with clinical suspicion of a mitochondrial disorder. These individuals had a similar, severe infantile and often lethal multi‐systemic disorder that included hypotonia, developmental delay, hypertrophic cardiomyopathy, progressive epileptic encephalopathy, progressive cerebral atrophy, and white matter abnormalities on brain MRI consistent with Leigh syndrome. cDNA studies showed a predominant shortened transcript with skipping of exon 2 and low levels of the normal full‐length transcript. Fibroblasts from the affected individuals demonstrated decreased ATP5PO protein, defective assembly of complex V with markedly reduced amounts of peripheral stalk proteins, and complex V hydrolytic activity. Further, expression of human ATP5PO cDNA without exon 2 (hATP5PO‐∆ex2) in yeast cells deleted for yATP5 (ATP5PO homolog) was unable to rescue growth on media which requires oxidative phosphorylation when compared to the wild type construct (hATP5PO‐WT), indicating that exon 2 deletion leads to a non‐functional protein. Collectively, our findings support the pathogenicity of the ATP5PO c.87+3A>G variant, which significantly reduces but does not eliminate complex V activity. These data along with the recent report of an affected individual with ATP5PO variants, add to the evidence that rare biallelic variants in ATP5PO result in defective complex V assembly, function and are associated with Leigh syndrome. [ABSTRACT FROM AUTHOR]

A temperature control unit was implemented to vary the temperature of samples studied on a commercial Mobile Universal Surface Explorer nuclear magnetic resonance (MOUSE‐NMR) apparatus. The device was miniaturized to fit the maximum MOUSE sampling depth (25 mm). It was constituted by a sample holder sandwiched between two heat exchangers placed below and above the sample. Air was chosen as the fluid to control the temperature at the bottom of the sample, at the interface between the NMR probe and the sample holder, in order to gain space. The upper surface of the sample was regulated by the circulation of water inside a second heat exchanger placed above the sample holder. The feasibility of using such a device was demonstrated first on pure water and then on several samples of bread dough with different water contents. For this, T1 relaxation times were measured at various temperatures and depths and were then compared with those acquired with a conventional compact closed‐magnet spectrometer. Discussion of results was based on biochemical transformations in bread dough (starch gelatinization and gluten heat denaturation). It was demonstrated that, within a certain water level range, and because of the low magnetic field strength of the MOUSE, a linear relationship could be established between T1 relaxation times and the local temperature in the dough sample. [ABSTRACT FROM AUTHOR]

This study presents a multidisciplinary survey combining geological fieldwork and geophysical data to better constrain the parameters influencing the morphology and behaviour of a retreating coastal cliff. Erosion rates are spatially highly variable and hard to predict because of the manifold parameters acting on them. Among these parameters, rock resistance exerts a paramount influence on cliff retreat. Characterizing the rock resistance distribution along a coastal region requires the mapping of several key subsurface properties including the bulk lithology, faulting, fracturing, or weathering. This is a difficult and expensive task because of the high spatial variability of these factors linked to the spatial complexity of the geology. Geophysical methods can be used to tackle this challenge by quickly providing the 3D visualization and distribution of these parameters within the subsurface. A fast‐eroding portion of the Norfolk coast (UK) at West Runton is investigated using a multidisciplinary approach, combining ground‐penetrating radar, electrical resistivity tomography (ERT), cone penetration tests, and outcrop studies. The results allowed us to build a 3D geological and geophysical model of a highly complex area of glacial geology. It forms part of a relict glaciotectonic thrust‐tip moraine and sand basin sequence. The surfaces interpreted on radar data are associated with strong resistivity contrasts on the ERT data. These contrasts have been attributed to petrophysical variations between the lithological units. The base of the sand basin is marked by a low‐permeability clay bed. Its low shear strength is likely to be more susceptible to failure, hereby accelerating the erosion rate of an already fast‐eroding sand basin. The resulting model can be used as input for locally constraining the ground parameters in coastal recession and erosion models. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of estimated fetal weight (EFW) charts at the third trimester ultrasound for detecting small‐ and large‐for‐gestational age (SGA/LGA) newborns with adverse outcomes. Design: Nationally representative observational study. Setting: French maternity units in 2016. Population: 9940 singleton live births with an ultrasound between 30 and 35 weeks of gestation. Methods: We compared three prescriptive charts (INTERGROWTH‐21st, World Health Organization (WHO), Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD]), four descriptive charts (Hadlock, Fetal Medicine Foundation, two French charts) and a French customised growth model (Epopé). Main outcome measures: SGA and LGA (birthweights <10th and >90th percentiles) associated with adverse outcomes (low Apgar score, delivery‐room resuscitation, neonatal unit admission). Results: 2.1% and 1.1% of infants had SGA and LGA and adverse outcomes, respectively. The sensitivity and specificity for detecting these infants with an EFW <10th and >90th percentile varied from 29–65% and 84–96% for descriptive charts versus 27–60% and 83–96% for prescriptive charts. WHO and French charts were closest to the EFW distribution, yielding a balance between sensitivity and specificity for SGA and LGA births. INTERGROWTH‐21st and Epopé had low sensitivity for SGA with high sensitivity for LGA. Areas under the receiving operator characteristics curve ranged from 0.62 to 0.74, showing low to moderate predictive ability, and diagnostic odds ratios varied from 7 to 16. Conclusion: Marked differences in the performance of descriptive as well as prescriptive EFW charts highlight the importance of evaluating them for their ability to detect high‐risk fetuses. Choice of growth chart strongly affected identification of high‐risk fetuses at the third trimester ultrasound. Choice of growth chart strongly affected identification of high‐risk fetuses at the third trimester ultrasound. Linked article This article is commented on by F Figueras, pp. 949 in this issue. To view this minicommentary visit https://doi.org/10.1111/1471-0528.17108. [ABSTRACT FROM AUTHOR]

Introduction: Customized intrauterine growth charts are widely used for growth monitoring and research. They are based on three assumptions: (1) estimated fetal weight (EFW) has a normal distribution with a constant coefficient of variation at all gestational ages; (2) Hadlock's growth curve accurately describes the relation between EFW and gestational ages; (3) associations between EFW and the fetal and maternal characteristics included in the customization model (fetal sex, pre‐pregnancy weight, height, parity) are proportional throughout pregnancy. The aim of this study was to test whether these underlying assumptions are verified. Material and methods: Data came from (1) the French Longitudinal Study of Children (ELFE) cohort, which recruited births after 32 weeks' gestation in 349 maternity hospitals in France in 2011, and (2) the National Perinatal Survey, which included births from all French maternity hospitals in 2016. The study population included, respectively, 6 920 and 8 969 singleton non‐malformed term live births with data on customization characteristics and EFW. We computed the coefficient of variation by gestational age and then modeled the association of gestational age, maternal and fetal characteristics with EFW at the second and third trimester ultrasound and with birthweight using linear regression. To assess the proportionality of the impact of maternal and fetal characteristics, we computed the percent change in weight associated with these characteristics at these three time points. Results: The coefficient of variation was close to 12% at each gestational age, but EFW was not normally distributed, leading to small but systematic underestimation of fetuses under the 10th percentile. Weights representing the 50th and 10th percentiles based on Hadlock's growth trajectory were lower than observed or predicted weights. Most characteristics more strongly impacted weight at birth than during pregnancy. In the French Longitudinal study of Children (ELFE) cohort, boys were 1.8% (95% confidence interval [CI] 1.3–2.4) heavier than girls in the third trimester, whereas this percentage was 4.6% (95% CI 4.0–5.2) at birth. In the National Perinatal Survey, these percentages were 2.3% (95% CI 1.8–2.8) and 4.3% (95% CI 3.8–4.8). Conclusions: These results from two independent sources revealed discrepancies between routine clinical EFW data used for growth monitoring and the customized growth model's assumptions. [ABSTRACT FROM AUTHOR]

Objective: Restoring anti‐JC virus (JCV) immunity is the only treatment of progressive multifocal leukoencephalopathy (PML). Interleukin‐7 is a cytokine that increases number and function of T cells. We analyzed a population of PML patients who received recombinant human IL‐7 (rhIL‐7) to estimate survival and its determinants. Methods: After exclusion of patients with missing data or receiving other immunotherapies, findings from 64 patients with proven PML who received rhIL‐7 between 2007 and 2020 were retrospectively analyzed. Logistic regression was used to analyze variables associated with one‐year survival. Results: Underlying conditions were HIV/AIDS (n = 27, 42%), hematological malignancies (n = 16, 25%), primary immunodeficiencies (n = 13, 20%), solid organ transplantation (n = 4, 6%) and chronic inflammatory diseases (n = 4, 6%). One‐year survival was 54.7% and did not differ by underlying condition. Survival was not associated with baseline characteristics, but with a >50% increase in blood lymphocytes (OR 4.1, 95%CI 1.2–14.9) and CD4+ T cells (OR 5.9, 95%CI 1.7–23.3), and a > 1 log copies/mL decrease in cerebrospinal fluid JCV DNA (OR 7.6, 95%CI 1.6–56.1) during the first month after rhIL‐7 initiation. Side effects were mainly local and flu‐like symptoms (n = 8, 12.5%) and PML‐immune reconstitution inflammatory syndrome (IRIS) (n = 5, 8%). Interpretation: In this non‐controlled retrospective study, survival did not differ from that expected in HIV/AIDS patients, but might have been improved in those with hematological malignancies, primary immunodeficiencies and transplant recipients. RhIL‐7 might have contributed to the increase in blood lymphocytes and decrease in CSF JCV replication that were associated with better survival. ANN NEUROL 2022;91:496–505 [ABSTRACT FROM AUTHOR]

Proline racemases (PRAC), catalyzing the l‐proline and d‐proline interconversion, are essential factors in eukaryotic pathogens such as Trypanosoma cruzi, Trypanosoma vivax, and Clostridioides difficile. If the discovery of irreversible inhibitors of T. cruzi PRAC (TcPRAC) led to innovative therapy of the Chagas disease, no inhibitors of CdPRAC have been discovered to date. However, C. difficile, due to an increased incidence in recent years, is considered as a major cause of health threat. In this work, we have taken into account the similarity between TcPRAC and CdPRAC enzymes to design new inhibitors of CdPRAC. Starting from (E) 4‐oxopent‐2‐enoic acid TcPRAC irreversible inhibitors, we synthesized 4‐aryl substituted analogs and evaluated their CdPRAC enzymatic inhibition against eleven strains of C. difficile. This study resulted in promising candidates and allowed for identification of (E)‐4‐(3‐bromothiophen‐2‐yl)‐4‐oxobut‐2‐enoic acid 20 that was chosen for complementary in vivo studies and did not reveal in vivo toxicity. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to assess if switching from a protease inhibitors (PI)‐based regimen to a PI‐free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication. Methods: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV‐1 viral load below 200 copies/mL while being PI‐treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI‐free regimen. Results: Among the 216 patients with past KS event and a history of HIV‐1 infection efficiently treated by a PI‐based regimen, 148 patients (68.5%) later switched to a PI‐sparing regimen. Their baseline characteristics were not different from non‐switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI‐treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/μL (range 225–560) for switching patients, compared with 362 and 136 cells/μL for the other two patients. Conclusions: In this large cohort of PLHIV with a history of KS and ART‐controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI‐containing ART regimen has been switched to a PI‐free regimen. Our results do not support a specific effect of PI on KS. [ABSTRACT FROM AUTHOR]

In order to understand mammalian evolution and compute a wide range of biodiversity indices, we commonly use the 'bioregion', a spatial division adapted to ecological and evolutionary constraints. While commonly conducted by neontologists, the establishment of bioregions in palaeontology is generally a secondary analysis, shaped on subjective time scales and areas specific to the investigated questions and groups. This heterogeneity, coupled with the scale‐dependency of biodiversity indices, prevents the clear identification of macroecological and macroevolutionary trends for large taxonomic groups like extinct mammals. Here we tackle this issue by providing a coherent framework for Neogene and Pleistocene mammals of the Old World following two steps: (1) a temporal scale adapted to mammalian evolutionary history (i.e. evolutionary fauna) is defined by poly‐cohort analysis; (2) bioregions are then computed for each evolutionary fauna by clustering, ordination and intermediate approaches at multiples spatial scales (i.e. continental to regional) for Eurasia and Africa. Additionally, providing a coherent framework for a wide range of mammalian datasets, our results show: (1) the synchronous emergence and fall of five mammalian evolutionary faunas identified at chronological scales varying from the epoch to the geological stage; (2) a transition from a longitudinal to a latitudinal biogeographical structuring between the Miocene and Pliocene, especially in Europe; (3) the long‐term affinity of southern Asian with African faunas, in sharp contrast with the modern Palaearctic bioregion extension; and (4) the establishment of a vast Mediterranean bioregion from fragmented areas in the Late Miocene to its full extent in the Pleistocene. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic exposed multiple shortcomings in national and international capacity to respond to an outbreak of infectious disease. See Table S1 for data by country. gl Some countries reported disruptions or changes of data procedures related to the pandemic that may impact on quality or completeness, particularly for preliminary data. In these cases, we asked for information about the availability of data to generate stillbirth, preterm birth, low birthweight and caesarean rates, as they are often available earlier than data on neonatal or infant deaths. When several sources were used to generate Euro-Peristat data, we requested information on birth data that could be used to generate stillbirth, preterm and low birthweight rates (as opposed to neonatal or infant deaths, which may become available later). [Extracted from the article]

A spatially resolved multimodal spectroscopic device was used on a two‐layered "hybrid" model made of ex vivo skin and fluorescent gel to investigate the effect of skin optical clearing on the depth sensitivity of optical spectroscopy. Time kinetics of fluorescence and diffuse reflectance spectra were acquired in four experimental conditions: with optical clearing agent (OCA) 1 made of polyethylene glycol 400 (PEG‐400), propylene glycol and sucrose; with OCA 2 made of PEG‐400 and dimethyl sulfoxide (DMSO); with saline solution as control and a "dry" condition. An increase in the gel fluorescence back reflected intensity was measured after optical clearing. Effect of OCA 2 turned out to be stronger than that of OCA 1, possibly due to DMSO impact on the stratum corneum keratin conformation. Complementary experimental results showed increased light transmittance through the skin and confirmed that the improvement in the depth sensitivity of the multimodal spectroscopic approach is related not only to the dehydration and refractive indices matching due to optical clearing, but also to the mechanical compression of tissues caused by the application of the spectroscopic probe. [ABSTRACT FROM AUTHOR]

Background: Progressive Supranuclear Palsy (PSP) is a rare progressive, fatal neurodegenerative 4‐repeat tauopathy. AZP2006 (INN: Ezeprogind) is a first‐in‐class disease‐modifying oral small molecule acting via its strong binding to the complex Progranulin (PGRN) / Prosaposin (PSAP), able to increase the circulating contents of PGRN (plasma and brain) in non‐clinical models. Preclinically, AZP2006 promotes neuron survival, synaptic function, decreases Tau hyperphosphorylation and reduces neuroinflammation (in vitro and in vivo models of Alzheimer's disease, PSP and Parkinson's disease). In healthy volunteers Phase 1 studies, AZP2006 was well tolerated with a good safety profile. Method: AZP2006 safety, tolerability and pharmacokinetic profiles in plasma, whole blood, and CSF were investigated in a randomized, double‐blind, placebo‐controlled, parallel group study comparing 2 doses of AZP2006 (60 mg once daily during the 12‐week treatment period and 80 mg once daily for 10 days followed by 50 mg once daily) with placebo in 36 men and women aged ≥40 years and ≤80 years diagnosed with probable or possible PSP. Patients were observed for an additional 12‐week follow‐up period (NCT04008355). In secondary objectives, CSF biomarkers including PGRN for the target engagement and markers of neurodegeneration (NfL, phospho‐tau T181) as well as markers of neuroinflammation (sTREM2, interleukins, etc.) were quantified. In addition, exploratory efficacy objectives evaluating clinical endpoints (PSP‐RS total, PSP Gait, PSP Ocular, CGI‐ds, Schwab and England ADL) were investigated. Result: AZP2006 was safe and well tolerated; no related SAEs were reported. PK profile confirmed the long AZP2006 half‐life (as predicted in a prior popPK model). High brain penetrance was observed and AZP2006 CSF expected levels were achieved. In addition, the target engagement was confirmed by significant increase (vs baseline) of PGRN plasma levels. A PD‐PK analysis is planned. Conclusion: AZP2006 treatment showed promising effects after a 3‐month‐treatment. Considering these promising results, an open‐labelled extension (OLE) was started (60 mg daily) in France. In addition, a larger Phase 2b/3 study in PSP patients testing AZP2006 efficacy over 12‐month‐treatment is under preparation. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the overuse of antenatal care is needed to improve its organisation to deal with limited medical resources and doctor shortages. Objectives: To assess the proportion of women who overuse antenatal care and the associations of overuse with maternal characteristics and the qualifications of healthcare providers. Methods: We used the 2016 National Perinatal Survey, a cross‐sectional population‐based survey, performed in all maternity units in France, including 13,132 women. Based on the French national guidelines, 6–8 antenatal visits were defined as adequate, 9–11 as high use, and ≥12 as overuse, while 3 ultrasounds were considered adequate, 4–5 as high use, and ≥6 as overuse. We performed binary modified Poisson regressions—with adequate care as the reference—including maternal social and medical characteristics and the healthcare professionals' qualifications. Results: After women with inadequate care were excluded, 19.2% of low‐risk women had at least 12 visits and 30.5% at least 6 ultrasounds. Overuse of visits was associated with primiparity, average to high income, less than good psychological well‐being, and care by an obstetrician. The risks of overuse of ultrasounds were higher among primiparous, women with average to high income and those receiving care from a public‐sector obstetrician (adjusted relative risk 1.17, 95% CI, 1.13, 1.21) or private obstetrician (adjusted relative risk 1.12, 95% CI, 1.07, 1.16), compared with a public‐sector midwife. Conclusions: Antenatal care overuse is very common in France and associated with some maternal characteristics and also the qualification of care provider. Antenatal care should be customised according to women's needs, in particular for primiparae and those with poor well‐being, and available medical resources. [ABSTRACT FROM AUTHOR]

Background: Regionalisation programmes aim to ensure that very preterm infants are born in level III units (inborn) through antenatal referral or transfer. Despite widespread knowledge about better survival without disability for inborn babies, 10%‐30% of women deliver outside these units (outborn). Objective: To investigate risk factors associated with outborn deliveries and to estimate the proportion that were probably or possibly avoidable. Methods: We used a national French population‐based cohort including 2205 women who delivered between 24 and 30+6 weeks in 2011. We examined risk factors for outborn delivery related to medical complications, antenatal care, sociodemographic characteristics and living far from a level III unit using multivariable binomial regression. Avoidable outborn deliveries were defined by pregnancy risk (obstetric history, antenatal hospitalisation) and time available for transfer. Results: 25.0% of women were initially booked in level III, 9.1% were referred, 49.8% were transferred, and 16.1% had outborn delivery. Risk factors for outborn delivery were gestational age <26 weeks (adjusted relative risk (aRR) 1.37, 95% confidence interval (CI) 1.13, 1.66), inadequate antenatal care (aRR 1.39, 95% CI 1.10, 1.81), placental abruption (aRR 1.66, 95% CI 1.27, 2.17), and increased distance to the closest level III unit ((aRR 2.79, 95% CI 2.00, 3.92) in the 4th versus 1st distance quartile). Among outborn deliveries, 16.7% were probably avoidable, and 25.6% possibly avoidable, which could increase the proportion of inborn deliveries between 85.9% and 92.9%. Avoidable outborn deliveries were mainly associated with gestational age, intrauterine growth restriction, preterm premature rupture of membranes, and haemorrhage, but not distance. Conclusions: Our study identified some modifiable risk factors for outborn delivery; however, when regionalised care relies heavily on antenatal transfer, as it does in France, only some outborn deliveries may be prevented. Earlier referral of high‐risk women will be needed to achieve full access to tertiary care. [ABSTRACT FROM AUTHOR]

A 1‐year‐old male Cane Corso was presented for progressive hindlimb neurologic deficits, with a history of suspected recurrent meningitis. Physical examination and advanced diagnostic imaging findings were suggestive of a thoracic dermoid sinus extending into the dura mater, and spina bifida. After initial medical treatment, the lesion was surgically excised, and the presence of an intramedullary cyst in continuation with the dermoid sinus was confirmed, requiring partial durectomy and myelotomy for removal. Histopathological examination of the excised tissue confirmed the diagnosis of a dermoid sinus associated with an intramedullary dermoid cyst. After surgery, the dog temporarily declined neurologically but then showed progressive neurological improvement. This report describes presentation and successful surgical treatment of a type IVa dermoid sinus associated with an intramedullary dermoid cyst and spina bifida in a dog. [ABSTRACT FROM AUTHOR]

Objective: Robson's Ten Group Classification System (TGCS) creates clinically relevant sub‐groups for monitoring caesarean birth rates. This study assesses whether this classification can be derived from routine data in Europe and uses it to analyse national caesarean rates. Design: Observational study using routine data. Setting: Twenty‐seven EU member states plus Iceland, Norway, Switzerland and the UK. Population: All births at ≥22 weeks of gestational age in 2015. Methods: National statistical offices and medical birth registers derived numbers of caesarean births in TGCS groups. Main outcome measures: Overall caesarean rate, prevalence and caesarean rates in each of the TGCS groups. Results: Of 31 countries, 18 were able to provide data on the TGCS groups, with UK data available only from Northern Ireland. Caesarean birth rates ranged from 16.1 to 56.9%. Countries providing TGCS data had lower caesarean rates than countries without data (25.8% versus 32.9%, P = 0.04). Countries with higher caesarean rates tended to have higher rates in all TGCS groups. Substantial heterogeneity was observed, however, especially for groups 5 (previous caesarean section), 6, 7 (nulliparous/multiparous breech) and 10 (singleton cephalic preterm). The differences in percentages of abnormal lies, group 9, illustrate potential misclassification arising from unstandardised definitions. Conclusions: Although further validation of data quality is needed, using TGCS in Europe provides valuable comparator and baseline data for benchmarking and surveillance. Higher caesarean rates in countries unable to construct the TGCS suggest that effective routine information systems may be an indicator of a country's investment in implementing evidence‐based caesarean policies. Many European countries can provide Robson's Ten‐Group Classification to improve caesarean rate comparisons. Many European countries can provide Robson's Ten‐Group Classification to improve caesarean rate comparisons. [ABSTRACT FROM AUTHOR]

Background: Introduction and gradual incremental escalation of a low dose of baked egg may accelerate the resolution of severe hen's egg (HE) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked egg oral immunotherapy (OIT) in children with HE allergy after a low‐dose baked egg oral food challenge (OFC). Methods: In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 71 children with HE allergy and high egg‐white (EW) and ovomucoid specific IgE levels, who underwent a total of 164 OFC (71 baked egg, then 93 unbaked egg). Mean age at first low‐dose baked egg OFC was 6 years. Median EW specific IgE was 14.0 kUA/L, and median ovomucoid specific IgE was 11.7 kUA/L. Results: Most children were treated with baked egg OIT. Our study shows that 78.9% of the children did not react to first low‐dose baked egg OFC (702 mg of HE protein). 8.7% of children discontinued OIT at home. Finally, desensitization to unbaked HE was achieved in 47 children (66.2% of children allergic to HE). Children with lower EW specific IgE levels had a significantly higher probability of becoming desensitized to HE. We did not report any anaphylactic reactions to baked egg OIT. Conclusion: Most children with HE allergy and high egg‐white (EW) and ovomucoïd specific IgE levels tolerate the introduction of baked egg. Baked egg OIT is safe, and anaphylaxis to baked egg OIT has not been observed. [ABSTRACT FROM AUTHOR]

Background: The renin‐angiotensin‐aldosterone system (RAAS), when chronically activated, is harmful and RAAS‐suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people. Hypothesis/Objectives: To determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE‐I), benazepril, and spironolactone, would be superior to benazepril alone. Animals: Five hundred and sixty‐nine client‐owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10‐days' duration. Methods: After initial stabilization, dogs were randomized into a positive‐controlled, double‐blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d. Results: A significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32‐0.98; P =.04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59‐0.89, P =.002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups. Conclusion and Clinical Importance: The combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs. [ABSTRACT FROM AUTHOR]

A 9‐year‐old spayed female crossbred dog was referred with a 6‐month history of polyuria/polydipsia associated with systemic arterial hypertension and hypokalaemia according to clinical and biochemical evaluations, respectively. Pheochromocytoma with concomitant unilateral nonsecreting thyroid carcinoma and ipsilateral nonsecreting parathyroid hyperplasia were diagnosed by ultrasonography, computed tomography, cytology and histopathology. Surgical treatment allowed for the complete resolution of clinical and biochemical abnormalities, and no recurrence was found during the one‐year clinical follow‐up. To the best of the author's knowledge, this is the third report describing multiple endocrine neoplasia type 2‐like syndrome in dogs, and it further characterizes this rare condition. [ABSTRACT FROM AUTHOR]

Introduced rodent populations pose significant threats worldwide, with particularly severe impacts on islands. Advancements in genome editing have motivated interest in synthetic gene drives that could potentially provide efficient and localized suppression of invasive rodent populations. Application of such technologies will require rigorous population genomic surveys to evaluate population connectivity, taxonomic identification, and to inform design of gene drive localization mechanisms. One proposed approach leverages the predicted shifts in genetic variation that accompany island colonization, wherein founder effects, genetic drift, and island‐specific selection are expected to result in locally fixed alleles (LFA) that are variable in neighboring nontarget populations. Engineering of guide RNAs that target LFA may thus yield gene drives that spread within invasive island populations, but would have limited impacts on nontarget populations in the event of an escape. Here we used pooled whole‐genome sequencing of invasive mouse (Mus musculus) populations on four islands along with paired putative source populations to test genetic predictions of island colonization and characterize locally fixed Cas9 genomic targets. Patterns of variation across the genome reflected marked reductions in allelic diversity in island populations and moderate to high degrees of differentiation from nearby source populations despite relatively recent colonization. Locally fixed Cas9 sites in female fertility genes were observed in all island populations, including a small number with multiplexing potential. In practice, rigorous sampling of presumptive LFA will be essential to fully assess risk of resistance alleles. These results should serve to guide development of improved, spatially limited gene drive design in future applications. [ABSTRACT FROM AUTHOR]

Boffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in coronavirus disease 2019 (COVID‐19) are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in patients with severe COVID‐19 than those reported in patients with HIV. These findings have led to a reduction of the dose of lopinavir in some patients, hypothesizing an inhibitory effect of inflammation on lopinavir metabolism. Unfortunately, changes in plasma protein binding were never investigated. We performed a retrospective cohort study. Data were collected from the medical records of patients hospitalized for COVID‐19 treated with lopinavir/ritonavir in intensive care units or infectious disease departments of Toulouse University Hospital (France). Total and unbound concentrations of lopinavir, C reactive protein, albumin, and alpha‐1‐acid glycoprotein (AAG) levels were measured during routine care on the same samples. In patients with COVID‐19, increased total lopinavir concentration is the result of an increased AAG‐bound lopinavir concentration, whereas the unbound concentration remains constant, and insufficient to reduce the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral load. Although international guidelines have recently recommended against using lopinavir/ritonavir to treat severe COVID‐19, the description of lopinavir pharmacokinetics changes in COVID‐19 is a textbook case of the high risk of misinterpretation of a total drug exposure when changes in protein binding are not taken into consideration. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to describe labor duration of women managed with current obstetric practices in a French national population‐based cohort and to assess the association of age and BMI on this duration. Methods: All women in the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. Duration of labor was defined as time between admission to the labor ward and birth. Duration of total labor and first and second stage of labor were described. Then, duration of labor was estimated according to maternal age and BMI, using Kaplan‐Meier's method and compared with the log‐rank test after stratification on parity. Intrapartum cesarean birth was considered as a censoring event. Multivariable modeling was performed using Cox's proportional hazard's method. Results: Data of 3120 nulliparous and 4385 multiparous women were analyzed. Median labor duration was 6.1 hours ([5th; 95th percentile]) [1.4; 12.6] and 3.1 hours [0.3; 8.5] in nulliparous and multiparous women. Multivariable Cox analysis showed no independent association of maternal age and duration of labor. Nulliparous obese women had significantly lower odds of having a shorter labor than women with a BMI < 25 kg/m2, HR: 0.75; 95% CI [0.64‐0.88], but BMI was not associated with labor duration in multiparous women. Conclusions: Our study provides important information for both women and care practitioners on what to expect when entering the labor ward. There appears to be little association between maternal characteristics and labor duration, with the exception of BMI in nulliparous women. [ABSTRACT FROM AUTHOR]

TANGO2 disease is a severe inherited disorder associating multiple symptoms such as metabolic crises, encephalopathy, cardiac arrhythmias, and hypothyroidism. The mechanism of action of TANGO2 is currently unknown. Here, we describe a cohort of 20 French patients bearing mutations in the TANGO2 gene. We found that the main clinical presentation was the association of neurodevelopmental delay (n = 17), acute metabolic crises (n = 17) and hypothyroidism (n = 12), with a large intrafamilial clinical variability. Metabolic crises included rhabdomyolysis (15/17), neurological symptoms (14/17), and cardiac features (12/17; long QT (n = 10), Brugada pattern (n = 2), cardiac arrhythmia (n = 6)) that required intensive care. We show previously uncharacterized triggers of metabolic crises in TANGO2 patients, such as some anesthetics and possibly l‐carnitine. Unexpectedly, plasma acylcarnitines, plasma FGF‐21, muscle histology, and mitochondrial spectrometry were mostly normal. Moreover, in patients' primary myoblasts, palmitate and glutamine oxidation rates, and the mitochondrial network were also normal. Finally, we found variable mitochondrial respiration and defective clearance of oxidized DNA upon cycles of starvation and refeeding. We conclude that TANGO2 disease is a life‐threatening disease that needs specific cardiac management and anesthesia protocol. Mechanistically, TANGO2 disease is unlikely to originate from a primary mitochondrial defect. Rather, we suggest that mitochondrial defects are secondary to strong extrinsic triggers in TANGO2 deficient patients. [ABSTRACT FROM AUTHOR]

Rare extreme "black swan" disturbances can impact ecosystems in many ways, such as destroying habitats, depleting resources, and causing high mortality. In rivers, for instance, exceptional floods that occur infrequently (e.g., so‐called "50‐year floods") can strongly impact the abundance of fishes and other aquatic organisms. Beyond such ecological effects, these floods could also impact intraspecific diversity by elevating genetic drift or dispersal and by imposing strong selection, which could then influence the population's ability to recover from disturbance. And yet, natural systems might be resistant (show little change) or resilient (show rapid recovery) even to rare extreme events – perhaps as a result of selection due to past events. We considered these possibilities in two rivers where native guppies experienced two extreme floods – one in 2005 and another in 2016. For each river, we selected four sites and used archived "historical" samples to compare levels of genetic and phenotypic diversity before vs. after floods. Genetic diversity was represented by 33 neutral microsatellite markers, and phenotypic diversity was represented by body length and male melanic (black) colour. We found that genetic diversity and population structure was mostly "resistant" to even these extreme floods; whereas the larger impacts on phenotypic diversity were short‐lived, suggesting additional "resilience". We discuss the determinants of these two outcomes for guppies facing floods, and then consider the general implications for the resistance and resilience of intraspecific variation to black swan disturbances. [ABSTRACT FROM AUTHOR]

Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID‐19 with hypertension/cardiovascular disease, particularly in Europe. The ACE‐CoV study was designed to assess this question. The study was conducted in the Covid‐Clinic‐Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS‐CoV‐2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid‐Clinic‐Toul included 263 patients. Among them, 111 were included in the ACE‐CoV study population. In OW‐PS‐adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73–3.33). It was 0.99 (95% CI: 0.68–1.45) for ACEIs and 1.64 (95% CI: 0.77–3.50) for ARBs. Analyses with weighting by the IPTW‐PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE‐CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID‐19 with a history of cardiovascular disease/arterial hypertension. [ABSTRACT FROM AUTHOR]

IgG removal significantly enhances detection of microarray allergen-specific IgE reactivity in patients' serum Keywords: allergy diagnosis; IgE; precision medicine EN allergy diagnosis IgE precision medicine 395 398 4 01/09/21 20210101 NES 210101 Allergen multiplex (AM) investigation is an excellent research tool and is now getting more importance in clinical practice.1 AM miniaturization using limited amounts of each allergen suggested competition between IgE and IgG, but data in humans are scarce.2,3 We investigated the effect of IgG depletion on specific (s) IgE levels measured with two AM. This could be due to the presence of IgE/IgG aggregates or anti-IgE IgG.4 Serum samples, before and after IgG depletion, were tested for sIgE with the ImmunoCAP SP TM sp ISAC (Thermo Fisher). [Extracted from the article]