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Le traitement du SAHCS reste un défi pour le clinicien. Le groupe d’experts souligne qu’il est impératif de préciser les étiologies et comorbidités du SAHCS et de les traiter spécifiquement quand cela est possible. La réflexion du groupe de travail a abouti à un arbre décisionnel de prise en charge thérapeutique lorsque le traitement étiologique n’est pas possible. Cet arbre décisionnel n’inclut volontairement pas de traitement alternatif non ventilatoire (médicamenteux ou autre), les données de la littérature sur ces options alternatives ne permettent pas d’établir leur place dans le traitement des SAHCS. Des recommandations sur les indications de mise en route d’un traitement et sur le suivi des patients sont proposées. Ce travail est basé sur la littérature disponible et l’expertise collective actuelles mais devra faire l’objet d’adaptations dans les années à venir compte tenu d’études en cours.

In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction.

Ammonia (NH3) is a commonly used industrial chemical to which exposure at high concentrations can result in severe skin damage. Moreover, high levels of ammonia in the human body can lead to hyperammonemia conditions and enhanced cancer metabolism. In this work, the toxicity mechanism of NH3has been studied against human dermal fibroblast (HDF) cells using surface-enhanced Raman spectroscopy (SERS). For this purpose, gold nanoparticles of size 50 nm have been prepared and used as probes for Raman signal enhancement, after being internalized inside HDF cells. Following the exposure to ammonia, HDF cells showed a significant variation in the protein ternary structure’s signals, demonstrating their denaturation and oxidation process, together with early signs of apoptosis. Meaningful changes were observed especially in the Raman vibrations of sulfur-containing amino acids (cysteine and methionine) together with aromatic residues. Fluorescence microscopy revealed the formation of reactive oxygen and nitrogen species in cells, which confirmed their stressed condition and to whom the causes of protein degradation can be attributed. These findings can provide new insights into the mechanism of ammonia toxicity and protein oxidation at a single-cell level, demonstrating the high potential of the SERS technique in investigating the cellular response to toxic compounds.

In this research, Raman imaging was employed to map various samples, and the resulting data were analyzed using a suite of automated tools to extract critical information, including intensity and signal-to-noise ratio. The acquired spectra were further processed to identify similarities and investigate patterns using principal component analysis. The objective of this study was to establish guidelines for investigating Raman imaging results, particularly when dealing with large datasets comprising thousands of relatively low-intensity spectra. The overall quality of the results was assessed, and representative locations were determined based on the main Raman bands. While automated software solutions are insufficient for removing baselines and fitting the data, statistical analysis proved to be a powerful tool for extracting valuable information directly from the raw spectral data. This approach enables the extraction of as much information as possible from large arrays of spectral data, even in complex cases where automated software may fall short. The findings of this study contribute to enhancing the analysis and interpretation of Raman imaging results, providing researchers with a robust methodology for extracting meaningful insights from complex datasets, reducing the amount of effort required during data interpretation and analysis.

Peripheral nerve damage results in the loss of sensorimotor and autonomic functions, which is a significant burden to patients. Furthermore, nerve injuries greater than the limiting gap length require surgical repair. Although autografts are the preferred clinical choice, their usage is impeded by their limited availability, dimensional mismatch, and the sacrifice of another functional donor nerve. Accordingly, nerve guidance conduits, which are tubular scaffolds engineered to provide a biomimetic environment for nerve regeneration, have emerged as alternatives to autografts. Consequently, a few nerve guidance conduits have received clinical approval for the repair of short-mid nerve gaps but failed to regenerate limiting gap damage, which represents the bottleneck of this technology. Thus, it is still necessary to optimize the morphology and constituent materials of conduits. This review summarizes the recent advances in nerve conduit technology. Several manufacturing techniques and conduit designs are discussed, with emphasis on the structural improvement of simple hollow tubes, additive manufacturing techniques, and decellularized grafts. The main objective of this review is to provide a critical overview of nerve guidance conduit technology to support regeneration in long nerve defects, promote future developments, and speed up its clinical translation as a reliable alternative to autografts.

Chromosome structure in mammals is thought to regulate transcription by modulating three-dimensional interactions between enhancers and promoters, notably through CTCF-mediated loops and topologically associating domains (TADs)1–4. However, how chromosome interactions are actually translated into transcriptional outputs remains unclear. Here, to address this question, we use an assay to position an enhancer at large numbers of densely spaced chromosomal locations relative to a fixed promoter, and measure promoter output and interactions within a genomic region with minimal regulatory and structural complexity. A quantitative analysis of hundreds of cell lines reveals that the transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship. Mathematical modelling suggests that nonlinearity might arise from transient enhancer–promoter interactions being translated into slower promoter bursting dynamics in individual cells, therefore uncoupling the temporal dynamics of interactions from those of transcription. This uncovers a potential mechanism of how distal enhancers act from large genomic distances, and of how topologically associating domain boundaries block distal enhancers. Finally, we show that enhancer strength also determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation. Our measurements establish general principles for the context-dependent role of chromosome structure in long-range transcriptional regulation.

Alzheimer’s disease (AD) is the most frequent cause of dementia in the elderly. Few cases are familial (FAD), due to autosomal dominant mutations in presenilin-1 (PS1), presenilin-2 (PS2) or amyloid precursor protein (APP). The three proteins are involved in the generation of amyloid-beta (Aβ) peptides, providing genetic support to the hypothesis of Aβ pathogenicity. However, clinical trials focused on the Aβ pathway failed in their attempt to modify disease progression, suggesting the existence of additional pathogenic mechanisms. Ca2+dysregulation is a feature of cerebral aging, with an increased frequency and anticipated age of onset in several forms of neurodegeneration, including AD. Interestingly, FAD-linked PS1 and PS2 mutants alter multiple key cellular pathways, including Ca2+signaling. By generating novel tools for measuring Ca2+in living cells, and combining different approaches, we showed that FAD-linked PS2 mutants significantly alter cell Ca2+signaling and brain network activity, as summarized below.

Wireless optoelectronic devices are fabricated by controlling the porosity of p-type silicon, enabling in vivo efficient, non-genetic optoelectronic modulation of peripheral nerve activity.

CMOS optical sensors devices are becoming increasingly important and popular for many different applications. Some of these devices are fabricated starting from SOI (Silicon On Insulator) wafers and using semiconductor manufacturing techniques. A common feature of the CMOS sensors is the isolating trench that protects the device from electrical noise. We report on the multistep etch process development to fabricate trenches deeper than usual, in order to isolate the sensor also from stray light interference. We focus the attention on unexpected features that originated during the Buried Oxide (BOX) etch.

Objective: Automated voxel-based analysis methods are used to detect cortical hypometabolism typical of Alzheimer’s Disease (AD) on FDG-PET brain scans. We compared the accuracy of two clinically validated tools for their ability to identify those MCI subjects progressing to AD at followup, to evaluate the impact of the analysis method on FDG-PET diagnostic performance. Methods: SPMGrid and BRASS (Hermes Medical Solutions, Stockholm, Sweden) were tested on 131 MCI and elderly healthy controls from the EADC PET dataset. The concordance between the tools was tested by correlating the quantitative parameters (z- and t-values), calculated by the two software tools, and by measuring the topographical overlap of the abnormal regions (Dice score). Three independent expert readers blindly assigned a diagnosis based on the two map sets. We used conversion to AD dementia as the gold standard. Results: The t-map and z-map calculated with SPMGrid and BRASS, respectively, showed a good correlation (R > .50) for the majority of individual cases (128/131) and for the majority of selected regions of interest (ROIs) (98/116). The overlap of the hypometabolic patterns from the two tools was, however, poor (Dice score .36). The diagnostic performance was comparable, with BRASS showing significantly higher sensitivity (.82 versus .59) and SPMGrid showing higher specificity (.87 versus .52). Conclusion: Despite similar diagnostic performance in predicting conversion to AD in MCI subjects, the two tools showed significant differences, and the maps provided by the tools showed limited overlap. These results underline the urgency for standardization across FDG-PET analysis methods for their use in clinical practice.

Purpose External dacryocystorhinostomy (ext-DCR) is still considered the gold standard in the treatment of distal lacrimal duct obstruction. Despite an overall high success rate, some patients do relapse after surgery and the ideal perioperative management has not been identified yet. The purpose of this study is to critically discuss the published evidence in the last five years on the medical and surgical management of external dacryocystorhinostomy. Furthermore, the drawbacks of the available literature and the perspectives in this field will be also highlighted.Methods Systematic review of the literature in the last 5 years by using PubMed and Google Scholar.Results A total of 64 articles were included. Many technical modifications and surgical refinements have been proposed but a formal comparison among the various techniques is hampered by methodological heterogeneity. The use of local anesthesia, and the perioperative adjunctive techniques to reduce the risk of restenosis are also gaining popularity but the level of evidence remains weak.Conclusion Ext-DCR offers satisfactory clinical outcomes even though there are many gray areas that need to be addressed in future high-quality studies.

Current understanding of chromosome folding is largely reliant on chromosome conformation capture (3C)-based experiments, where chromosomal interactions are detected as ligation products after chromatin crosslinking. To measure chromosome structure in vivo, quantitatively and without crosslinking and ligation, we implemented a modified version of DNA adenine methyltransferase identification (DamID) named DamC, which combines DNA methylation-based detection of chromosomal interactions with next-generation sequencing and biophysical modeling of methylation kinetics. DamC performed in mouse embryonic stem cells provides the first in vivo validation of the existence of topologically associating domains (TADs), CTCF loops and confirms 3C-based measurements of the scaling of contact probabilities. Combining DamC with transposon-mediated genomic engineering shows that new loops can be formed between ectopic and endogenous CTCF sites, which redistributes physical interactions within TADs. DamC provides the first crosslinking- and ligation-free demonstration of the existence of key structural features of chromosomes and provides novel insights into how chromosome structure within TADs can be manipulated. A modified version of DamID allows measurement of chromosomal interactions without crosslinking and ligation, and provides validation for the existence of TADs in mESCs.

IntroductionPreventing in-flight hypoxia in pilots is typically achieved by wearing oxygen masks. These masks must be as comfortable as possible to allow prolonged and repeated use. The consequences of mask-induced facial contact pressure have been extensively studied, but little is known about mask-induced breathing discomfort. Because breathlessness is a strong distractor and engages cerebral resources, it could negatively impact flying performances.MethodsSeventeen volunteers (age 20–32) rated respiratory discomfort while breathing with no mask and with two models of quick-donning full-face crew oxygen masks with regulators (mask A, mask B). Electroencephalographic recordings were performed to detect a putative respiratory-related cortical activation in response to inspiratory constraint (experiment 1, n=10). Oxygen consumption was measured using indirect calorimetry (experiment 2, n=10).ResultsWith mask B, mild respiratory discomfort was reported significantly more frequently than with no mask or mask A (experiment 1: median respiratory discomfort on visual analogue scale 0.9 cm (0.5–1.4), experiment 1; experiment 2: 2 cm (1.7–2.9)). Respiratory-related cortical activation was present in 1/10 subjects with no mask, 1/10 with mask A and 6/10 with mask B (significantly more frequently with mask B). Breathing pattern, sigh frequency and oxygen consumption were not different.ConclusionsIn a laboratory setting, breathing through high-end aeronautical full-face crew oxygen masks can induce mild breathing discomfort and activate respiratory-related cortical networks. Whether or not this can occur in real-life conditions and have operational consequences remains to be investigated. Meanwhile, respiratory psychometric and neuroergonomic approaches could be worth integrating to masks development and evaluation processes.

A striking feature of rivers is their ability to sort the sediments composing them. One of the chief causes for grain sorting consists in the selective transport of different sizes moving downstream. This process can be substantially influenced by the presence of lateral topographic variations, as those produced by channel bifurcations, in which water and sediment are diverted between two smaller anabranches. In particular, field and laboratory observations have shown that the asymmetric flux distribution commonly observed in actual bifurcations is associated with a coarsening of the most‐carrying branch. Here, equilibrium sorting in river bifurcations is addressed through a quasi‐2D model. Differently from previous works, a fully physically based description of the processes tied to a heterogeneous sediment mixture is introduced. The main mechanisms consist in the lateral pull of sediment due to a sloping bed upstream the bifurcation, and the variation of transport capacity in downstream branches. The model indicates that grain sorting tends to reduce the degree of flux asymmetry between branches for increasing heterogeneity of the mixture. Moreover, the uneven discharge distribution is associated with a different bed surface composition, with bed coarsening of the dominating channel and fining of the other branch. The reduced sediment transport asymmetry and bed surface fining enhance the transport of fine material in the less‐carrying branch, thus contributing to keep it morphologically active. Finally, the model predicts an overall fining of bed surface material with respect to the feeder channel. River bifurcations occur when the main channel course splits into two secondary branches. The partition of sediments between these branches is essential to define whether bifurcations are morphologically stable in time, preventing sedimentation, and abandonment of the smaller channel. In this paper, we formulate a mathematical model to study how sediments of different sizes divide at bifurcations in morphodynamic equilibrium. Specifically, we consider two classes of sediment particles (e.g., fine and coarse gravel) and we investigate the role of the key mechanisms driving the sediment transport: the gravitational effect, which tends to move downhill coarse particles; and the selective transport effect, which promotes the mobility of coarse particles within the most‐carrying branch. These two mechanisms are found to bring contrasting effects, but the net results are clear. First, flow asymmetry is found to reduce with respect to the case where sediment particles of uniform size are considered. Second, the bed composition of the smaller branch becomes finer, contributing to maintain a significant sediment transport. These effects can explain patterns observed in gravel‐bed river bifurcations, and suggest how adjustments of bed composition can contribute to maintaining all branches active in the long term. Grain sorting reduces water and sediment flux asymmetry between downstream bifurcatesThe less‐carrying branch undergoes significant fining, which enhances its sediment transport capacityThe overall bed composition of downstream branches is finer than that of the feeder channel Grain sorting reduces water and sediment flux asymmetry between downstream bifurcates The less‐carrying branch undergoes significant fining, which enhances its sediment transport capacity The overall bed composition of downstream branches is finer than that of the feeder channel

The organic/inorganic interface in thin nanosized porous structures has a key role in determining the final properties of the composite materials. By use of the porous silicon/eumelanin hybrids as a case study, the role of this interface was investigated by experimental and computational methods. Our results show that an increased polymer density close to the hybrid interface strongly modifies the diffusion of the chemical species within the polymer molecule, affecting then the oxidation level of the pores’ inner Si surface. We observed a greater stability induced by increased pore diameter, a behavior that with computational and chemical arguments we attributed to a modified diffusion of the hydrogen peroxide toward the Si/eumelanin interface. Our results show that the overall behavior of a polymer when inserted in a tiny nanoscale structure must be taken into account for a correct understanding and control of the hybrids properties and that the formation of the interface alone may not be sufficient.

Measurement and estimation of bed load transport in gravel bed rivers are highly affected by its temporal fluctuations. Such variability is primarily driven by the flow regime but is also associated with a variety of inherent channel processes, such as flow turbulence, grain entrainment, and bed forms migration. These internal and external controls often act at comparable time scales, and are therefore difficult to disentangle, thus hindering the study of bed load variability under unsteady flow regime. In this paper, we report on laboratory experiments performed in a large, mobile bed flume where typical hydromorphological conditions of gravel bed rivers were reproduced. Data from a large number of replicated runs, including triangular and square-wave hydrographs, were used to build a statistically sound description of sediment transport processes. We found that the inherent variability of bed load flux strongly depends on the sampling interval, and it is significantly higher in complex, wandering or braided channels. This variability can be filtered out by computing the mean response over the experimental replicates, which allows us to highlight two distinctive phenomena: (i) an overshooting (undershooting) response of the mean bed load flux to a sudden increase (decrease) of discharge, and (ii) a clockwise hysteresis in the sediment rating curve. We then provide an interpretation of these findings through a conceptual mathematical model, showing how both phenomena are associated with a lagging morphological adaptation to unsteady flow. Overall, this work provides basic information for evaluating, monitoring, and managing gravel transport in morphologically active rivers. Bed load transport exhibits an inherent variability that depends on discharge and bed morphologyAdaptation of bed topography to unsteady flow produces hysteresis in the bed load rating curveThe clockwise hysteresis depends on flood duration relative to the time scale of bed evolution

AbstractThe Rosalia longicorn (Rosalia alpina) is a strictly protected saproxylic beetle, widely distributed in Central and Southern Europe and mainly associated with ancient beech forests. To improve knowledge about the conservation status of R. alpinain Italy, available molecular markers (microsatellites and mitochondrial cytochrome c oxidase I(COI)) were tested for the first time on Italian populations. The study was performed in four sampling sites distributed in two areas placed in Northern (“Foreste Casentinesi” National Park) and Central Apennines (“Abruzzo, Lazio and Molise” National Park) where populational data about Rosalia longicorn were collected in the framework of the European LIFE MIPP Project. The genetic relationship among Apennine and Central/South-eastern European populations was explored by a comparison with mitochondrial DNA (mtDNA) data from literature. Microsatellite markers were only partially informative when applied to R. alpinaItalian individuals, although providing some preliminary indication on an extensive gene flow among populations from the Apennines and local ongoing processes of genetic erosion. Genetic data are consistent with previous ecological data suggesting that the maintenance of variability in this species could be related to both habitat continuity and preservation of large senescent or standing dead trees in forests. Finally, a peculiar origin of the Apennine populations of R. alpinafrom a putative “Glacial Refugium” in Italy was inferred through COI data. The high genetic distance scored among the analysed populations and those from Central and South-eastern Europe indicates that the R. alpinademe from Apennine Mountains might represent a relevant conservation unit in Europe. Further genetic analyses will allow assessing other possible conservation units of R. alpinaand, thus, defining large-scale conservation strategies to protect this endangered longhorn beetle in Europe.

IMPORTANCE: It is unclear whether female carriers of the apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established. OBJECTIVE: To determine how sex and APOE genotype affect the risks for developing MCI and AD. DATA SOURCES: Twenty-seven independent research studies in the Global Alzheimer’s Association Interactive Network with data on nearly 58 000 participants. STUDY SELECTION: Non-Hispanic white individuals with clinical diagnostic and APOE genotype data. DATA EXTRACTION AND SYNTHESIS: Homogeneous data sets were pooled in case-control analyses, and logistic regression models were used to compute risks. MAIN OUTCOMES AND MEASURES: Age-adjusted odds ratios (ORs) and 95% confidence intervals for developing MCI and AD were calculated for men and women across APOE genotypes. RESULTS: Participants were men and women between ages 55 and 85 years. Across data sets most participants were white, and for many participants, racial/ethnic information was either not collected or not known. Men (OR, 3.09; 95% CI, 2.79-3.42) and women (OR, 3.31; CI, 3.03-3.61) with the APOE ε3/ε4 genotype from ages 55 to 85 years did not show a difference in AD risk; however, women had an increased risk compared with men between the ages of 65 and 75 years (women, OR, 4.37; 95% CI, 3.82-5.00; men, OR, 3.14; 95% CI, 2.68-3.67; P = .002). Men with APOE ε3/ε4 had an increased risk of AD compared with men with APOE ε3/ε3. The APOE ε2/ε3 genotype conferred a protective effect on women (OR, 0.51; 95% CI, 0.43-0.61) decreasing their risk of AD more (P value = .01) than men (OR, 0.71; 95% CI, 0.60-0.85). There was no difference between men with APOE ε3/ε4 (OR, 1.55; 95% CI, 1.36-1.76) and women (OR, 1.60; 95% CI, 1.43-1.81) in their risk of developing MCI between the ages of 55 and 85 years, but women had an increased risk between 55 and 70 years (women, OR, 1.43; 95% CI, 1.19-1.73; men, OR, 1.07; 95% CI, 0.87-1.30; P = .05). There were no significant differences between men and women in their risks for converting from MCI to AD between the ages of 55 and 85 years. Individuals with APOE ε4/ε4 showed increased risks vs individuals with ε3/ε4, but no significant differences between men and women with ε4/ε4 were seen. CONCLUSIONS AND RELEVANCE: Contrary to long-standing views, men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing AD from age 55 to 85 years, but women have an increased risk at younger ages.

We tested the application of the concept of hemeroby and generalism at community level, on a set of birds occurring in various habitats of central Italy characterized by different level of disturbance. In each habitat-related bird community, we applied the recently published species-specific score in hemeroby (a proxy of habitat-related disturbance; HSi) and hemerobiotic diversity (a proxy of generalism; H’Hi) to local species frequency, obtaining weighted values at community level (HStotand H’Htot). The relationship between HStotvs. H’Htotshowed an increasing trend moving from reed beds through forests and mosaics to urban communities. Quadratic model (best fit) evidenced a significant correlation between these variables and a tendency toward a hump-shaped curve, corroborating results already observed at species level (intermediate generalism hypothesis). The co-inertia analysis discriminated four groups of habitat-related communities, characterized by species with different levels of disturbance-sensitivity (expressed by HSi) and generalism (expressed by hemerobiotic diversity; H’Hi): (i) forest type-related, where mature wood communities were separated from a coppiced wood one; (ii) communities of moderately disturbed agricultural habitats; (iii) communities embedded in highly disturbed mosaics, and (iv) a group including either a highly disturbed urban habitat or a low disturbed wetland reed bed, with highly specialized species (respectively, synanthropic species and water-related species). Total scores in hemeroby and hemerobiotic diversity, expressing the composition in species with different disturbance preference and generalism, might act as good community-based indicators of degree of naturalness, especially for forest habitat types.

Longitudinal and transverse relaxivities of solid lipid nanoparticles loaded with superparamagnetic iron oxide nanoparticles (SPION-SLNs) were thoroughly investigated with the aim of understanding the main parameters regulating the potential negative contrast properties of these systems. In particular, the longitudinal relaxivity (r1) of water protons in the 10 kHz to 35 MHz frequency range was determined by 1H fast field-cycling NMR, while transverse relaxivity (r2) was measured at 21 MHz. The reproducibility and stability of SPION-SLNs was also tested on samples arising from independent preparations and at different times after preparation. Water diffusion in proximity of superparamagnetic nanoparticles was found to be the mechanism of proton nuclear relaxation enhancement and characteristic parameters were quantitatively determined by fitting the experimental data acquired on different samples as a function of concentration and temperature. Although a variation ascribable to the formation of clusters with a different number of SPIONs inhomogeneously embedded in the lipid matrix was observed among different preparations, the relaxivity properties of the investigated SPION-SLNs were found to be better than those of SPION-based contrast agents commonly considered as standard in the literature, and remained stable for at least 2 months.

La fatigue est l’un des symptômes les plus invalidants de la sclérose en plaques (SEP). Le syndrome d’apnées du sommeil (SAS) peut être présent chez des patients atteints de SEP et pourrait contribuer à cette fatigue.

Climate change is expected to alter the distribution of flow discharge in rivers worldwide. We study the impact of climate‐driven flow changes on the shape of riverbed, and specifically on alternate bars, large deposits of gravel/sand that often form in rivers. We consider the illustrative example of the Alpine Rhine River, showing two nearby reaches with similar hydro‐morphological characteristics, but different channel width. Hydrological projections are obtained from literature, while the evolution of alternate bars is predicted through a novel, semi‐analytical model. Results show a remarkably different behavior of the two reaches: the upstream one, being wide enough for a full development of alternate bars, is resistant to flow alterations; the downstream reach, whose width is close to threshold conditions, is highly susceptible to future changes, showing a strong tendency to increase bar prominence. These findings reflect a general tendency of near‐threshold geomorphic systems to be vulnerable to anthropic stressors. The worldwide alteration of the river flow induced by climate change is likely to significantly impact the bed morphology of embanked rivers, which is often characterized by the presence of alternate bars, namely repetitive sequences of large sediment deposits and scour zones. Bar formation is both a major issue for river management (due to local erosion at instream structures and increase of flood risk), and an important resource for sustaining biodiversity, because bar morphology templates rich habitats for river fauna and vegetation. We analyze the effect of climate change on river bars by considering existing state‐of‐the‐art projections of future flow discharge, and by implementing a mathematical model suitable to perform long‐term simulations, while keeping the essential ingredients to reproduce bar dynamics. Model results reveal a very different adaptation of the riverbed to climate change: relatively wide reaches are expected to maintain the current alternate bar characteristics, while reaches whose width is close to a critical threshold value are likely to experience a remarkable alteration in the next decades, which provides a noteworthy example of how near‐threshold geomorphic systems may be highly sensitive to climate change. Climate‐driven changes of hydrological regime can have a significant impact on bar morphologyThe formation of alternate bars in channelized rivers is promoted by a decrease of frequency of high flowsSensitivity of bar morphology to climatic stressors depends on how far the river width is from the key morphodynamic threshold value Climate‐driven changes of hydrological regime can have a significant impact on bar morphology The formation of alternate bars in channelized rivers is promoted by a decrease of frequency of high flows Sensitivity of bar morphology to climatic stressors depends on how far the river width is from the key morphodynamic threshold value

The severity and transmissibility of COVID-19 justify the need to identify the factors associated with its cost of illness (CoI).

A 1-year-old, 5-kg, intact male Lhassa Apso dog was presented to the author's institution with a 10- days history of dysorexia, vomiting and diarrhea. The patient did not have any history of former disease, previous abdominal surgery, or trauma. Abdominal ultrasonographic examination revealed intestinal obstruction. Exploratory laparotomy was subsequently performed. A loop of jejunum was incarcerated through a 10-cm in diameter mesenteric defect with secondary intestinal strangulation and concomitant partial mesenteric torsion. This was reduced without the need for intestinal resection. Closure of the mesenteric defect was performed using an omental pedicle flap elevated from the left gastroepiploic artery. The dog made an uneventful recovery. At the last telephone follow-up 8 months after surgery, the dog was in excellent physical condition with no recurrence of clinical signs. This is the first reported case of congenital trans-mesenteric hernia in a dog.

Understanding the role of external controls on the morphology of braided rivers is currently limited by the dearth of robust metrics to quantify and distinguish the diversity of channel form. Most existing measures are strongly dependent on river stage and unable to account for the three‐dimensional complexity that is apparent in digital terrain models of braided rivers. In this paper, we introduce a simple, stage‐independent morphological indicator that enables the analysis of reach‐scale regime morphology as a function of slope, discharge, sediment size, and degree of confinement. The index is derived from the bed elevation frequency distribution and characterizes a statistical width‐depth curve averaged longitudinally over multiple channel widths. In this way, we define a “synthetic channel” described by a simple parameter that embeds information about the river morphological complexity. Under the assumption of uniform flow, this approach can be extended to provide estimates of the reach‐averaged shear stress distribution, bed load flux, and at‐a‐station‐variability of wetted width. We test this approach using data from a wide range of labile channels including 58 flume experiments and three gravel bed braided rivers. Results demonstrate a strong relationship between the unit discharge and the shape of the elevation distribution, which varies between a U shape for typical single‐thread confined channels and a Y shape for multithread reaches. Finally, we discuss the use of the metric as a diagnostic index of river condition that may be used to support inferences about the river morphological trajectory. Reach‐averaged braided river morphology is explored using flume and field data, and numerical modelsWe introduce a reach‐scale index based on bed geometry and we test how it changes with key controlsThis enables to estimate bed shear stress and at‐a‐station variability of bed load flux and width

In this work, we prove that, for a current regime of 10 μA and using industry‐relevant programming pulse‐width, Cu/Al2O3‐based conductive‐bridging RAM (CBRAM) cells ensure reliably larger memory window (MW) than state‐of‐the‐art oxygen‐vacancy‐based RRAM (OxRRAM) cells. Due to the intrinsically stochastic nature of the switching mechanism, the Ronand Roffvalues can be widely distributed, especially in a low‐current regime, drastically reducing the overall memory window. For this reason, in this study we adopt a statistical approach, focusing on the tails of the distributions. Using a program‐verify method we show that the larger median MW in CBRAM allows to program a MW ≥×10 using ×10 shorter programming time with respect to OxRRAM. Moreover, we show that, in order to ensure a MW >×10 after a fixed retention time, the programming time needs to be several decades larger for OxRRAM than for CBRAM.

In this paper, we introduce rare‐earth hygroscopic oxide Gd2O3as a novel switching material allowing extended reset operation as compared to standard state‐of‐the‐art oxide like (Hf,Al)O2. We prepared 5 nm‐thick oxide layers, as integrated between TiN and Hf electrodes in 1‐transistor/1‐resistor configuration. Using industry‐relevant programming current I≤ 10 µA and pulse width ≤1 µs, 40 nm‐size TiN\Gd2O3\Hf cells allowed reaching a median memory window (MW) > × 70 while state‐of‐the‐art materials exhibited MW < × 10 in the same conditions. Based on the large MW, high write endurance properties (>106cycles), and good retention of Gd2O3‐based cells (>5 days at 85 °C), verify algorithms allow reliable programming with low latency.

We previously showed in heart failure (HF) patients that obstructive respiratory events during sleep and generation of negative intrathoracic pressure during Mueller manoeuvres, mimicking obstructive apneas, acutely reduced stroke volume (SV). We also showed that treating obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) increased left ventricular ejection fraction over a 1-month period. We therefore hypothesized that, in HF patients, those with OSA would have greater overnight declines in SV and cardiac output (CO) than in those without sleep apnea, and that therapy of OSA using CPAP would prevent these declines.

La prévalence des apnées obstructives du sommeil est plus élevée chez les patients présentant une rétention hydrosodée, telle que l’insuffisance cardiaque chronique (ICC), que dans la population générale. Chez les patients en ICC, les apnées centrales, rares en population générale, sont également fréquentes. Quoique la physiopathologie des apnées centrales et obstructives soit multifactorielle, ces observations suggèrent que la rétention des fluides contribue au développement des deux types d’apnées chez ces patients. En particulier, l’excès de fluide accumulé dans les jambes pendant le temps passé en position verticale peut être redistribué selon un axe caudorostral en position allongée, tout au long de la nuit. Une partie de ces fluides peut atteindre le cou, augmentant la pression tissulaire autour des voies aériennes supérieures et prédisposant aux apnées obstructives. Chez les patients en ICC, les fluides peuvent également s’accumuler au niveau des poumons entraînant une hyperventilation à l’origine d’une baisse de la PaCO2 au-dessous du seuil apnéique, conduisant à l’apparition d’apnées centrales. Cet article a pour but de faire le point sur les différentes études ayant exploré le rôle du transfert de fluide dans la genèse des apnées tant obstructives que centrales.

The awareness of the importance of deadwood in forest ecosystems has increased in recent decades. Today, dead wood is recognized as a key factor affecting diversity of forest communities. Hole-nesting birds and saproxylic organisms represent an active part of the animal community through the recycle of decaying wood into the forest soils. Three relict beech forests of central Italy were surveyed for both saproxylic beetles and hole-nesting birds, using two different types of interception traps for the former group and point count method for the latter. The variables of dead wood quality were recorded from ten plots, particularly the decaying class and typology of all the wood debris with a diameter = 5 cm. In order to correlate richness and abundance of beetles and birds in a symmetric way, we used co-inertia analysis (CoIA). To correlate in a predictive way the dead wood attributes (dead wood typology and class decay) with birds and beetles assemblages we used partial redundancy analysis (RDA). Our results showed a significant relationship between saproxylic beetle and hole-nesting bird communities. Three dead wood variables (the volume of standing dead trees, stumps and large branches on the ground) appeared to be good predictors of saproxylic beetle richness while the volume of standing dead tree and of dead trees on the ground were the same for hole-nesting birds. These results suggest specific recommendations useful for forest management and planning.

Looping patterns, where channels divide and reconnect further downstream, are widespread in natural rivers. Here, we build an extensive dataset of different gravel‐bed and sand‐bed rivers around the world encompassing a wide range of physiographic and sedimentological conditions. Field data show the existence of quasi‐universal relations for the anabranches length when scaled with bankfull hydraulic geometry variables of the main upstream channel. The dimensionless length is found to be nearly slope‐invariant, identifying a clear difference with respect to deltaic systems. This scaling relationship is explained by interpreting the dynamics of river loops as basically controlled by a two‐way interaction between their constitutive elements, bifurcations and confluences. The identification of a quasi‐universal length scale provides insight on the morphological evolution of multi‐thread networks and constitutes a key information for the design of self‐sustaining river restoration interventions. River loops, where the water course splits into smaller branches that reconnect further downstream, are ubiquitous in natural environments. A deeper understanding of their spatial structure can greatly improve the effectiveness and sustainability of common practices in river restoration, where multiple channels are reactivated to recover the ecological functions of harmed riverine ecosystems. The analysis of many different rivers worldwide shows that the length of river loops is not randomly distributed but follows a characteristic law. In particular, the average length of bifurcating branches is found to be proportional to the hydraulic parameters (width, depth) of the main upstream channel, regardless of the specific climatic or geologic context. This relationship is explained in terms of the key physical mechanisms that control the distribution of water and sediment between the branches. River anabranches show a characteristic length set by bankfull hydraulic geometry parameters of the main channelThe anabranches length is unrelated to backwater length, thus marking a clear difference with respect to deltaic systemsField evidence is theoretically explained as the result of morphodynamic interaction between bifurcation and confluence nodes River anabranches show a characteristic length set by bankfull hydraulic geometry parameters of the main channel The anabranches length is unrelated to backwater length, thus marking a clear difference with respect to deltaic systems Field evidence is theoretically explained as the result of morphodynamic interaction between bifurcation and confluence nodes

We report on the fabrication and characterization of a freestanding ultrathin, mucoadhesive gold nanoshell/polysaccharide multilayer nanocomposite (thermonanofilm, TNF), that can be used for controlled photothermal ablation of tissues through irradiation with near-infrared radiation (NIR) laser. The aim of this work is to provide a new strategy to precisely control particle concentration during photothermalization of cancerous lesions, since unpredictable and aspecific biodistributions still remains the central issue of inorganic nanoparticle-assisted photothermal ablation. Gold nanoshell encapsulation in polysaccharide matrix is achieved by drop casting deposition method combined with spin-assisted layer-by-layer (LbL) assembly. Submicrometric thickness of films ensures tissue adhesion. Basic laser-induced heating functionality has been demonstrated by in vitroTNF-mediated thermal ablation of human neuroblastoma cancer cells, evidenced by irreversible damage to cell membranes and nuclei. Ex vivolocalized vaporization and carbonization of animal muscular tissue is also demonstrated by applying TNF onto tissue surface. Thermal distribution in the tissue reaches a steady state in a few seconds, with significant increases in temperature (ΔT> 50) occurring across an 1 mm span, ensuring control of local photothermalization and providing more safety and predictability with respect to traditional laser surgery. A steady-state model of tissue thermalization mediated by TNFs is also introduced, predicting the temperature distribution being known the absorbance of TNFs, the laser power, and the tissue thermal conductivity, thus providing useful guidelines in the development of TNFs. Thermonanofilms can find applications for local photothermal treatment of cancerous lesions and wherever high precision and control of heat treatment is required.

Les troubles respiratoires (TbR) sont peu décrits chez les patients atteints de SEP, bien qu’ils jouent un rôle primordial dans le fardeau de la maladie. Première cause de mortalité, ils peuvent subitement s’aggraver, en cas d’infection pulmonaire par exemple.

Le port d’une compression aux membres inférieurs réduit l’index d’apnées-hypopnées (IAH) dans le syndrome d’apnée-hypopnée obstructive du sommeil (SAHOS). Ceci serait expliqué par la réduction de la précharge lymphatique nocturne au niveau du cou prévenant son augmentation de volume et l’obstruction du pharynx qui peut en résulter.

Le syndrome d’apnées obstructives du sommeil (SAOS) est considéré un facteur de risque cardiovasculaire. La fermeture répétée des voies aériennes supérieures pendant le sommeil déclenche des phénomènes physiopathologiques responsables d’un déséquilibre sympathovagal, médiateur central des conséquences cardiovasculaires. Par contre, l’effet de la CPAP sur les complications cardiovasculaires reste controversé. Une explication proposée est que l’index d’apnées-hypopnées (IAH) pourrait être insuffisant à représenter les phénomènes à l’origine des effets cardiovasculaires. Notre objectif est de tester la capacité d’une manœuvre de deep breathing (DB) à montrer une dysfonction autonomique chez des patients SAOS, en comparaison aux analyses classiques de la variabilité du rythme cardiaque (HRV).

The unprecedented growth, availability and accessibility of imaging data from people with neurodegenerative conditions has led to the development of computational infrastructures, which offer scientists access to large image databases and e-Science services such as sophisticated image analysis algorithm pipelines and powerful computational resources, as well as three-dimensional visualization and statistical tools. Scientific e-infrastructures have been and are being developed in Europe and North America that offer a suite of services for computational neuroscientists. The convergence of these initiatives represents a worldwide infrastructure that will constitute a global virtual imaging laboratory. This will provide computational neuroscientists with a virtual space that is accessible through an ordinary web browser, where image data sets and related clinical variables, algorithm pipelines, computational resources, and statistical and visualization tools will be transparently accessible to users irrespective of their physical location. Such an experimental environment will be instrumental to the success of ambitious scientific initiatives with high societal impact, such as the prevention of Alzheimer disease. In this article, we provide an overview of the currently available e-infrastructures and consider how computational neuroscience in neurodegenerative disease might evolve in the future.

Free alternate bars are large‐scale, downstream‐migrating bedforms characterized by an alternating sequence of three‐dimensional depositional fronts and scour holes that frequently develop in rivers as the result of an intrinsic instability of the erodible bed. Theoretical models based on two‐dimensional shallow water and Exner equations have been successfully employed to capture the bar instability phenomenon, and to estimate bar properties such as height, wavelength and migration rate. However, the mathematical complexity of the problem hampered the understanding of the key physical mechanisms that sustain bar formation. To fill this gap, we considered a simplified version of the equations, based on neglecting the deformation of the free surface, which allows us to: (a) provide the first complete explanation of the bar formation mechanism as the result of a simple bond between variations of the water weight and flow acceleration; (b) derive a simplified, physically based formula for predicting bar formation in a river reach, depending on channel width‐to‐depth ratio, Shields number and relative submergence. Comparison with an unprecedented large set of laboratory experiments reveals that our simplified formula appropriately predicts alternate bar formation in a wide range of conditions. Noteworthy, the hypothesis of negligible free surface effect also implies that bar formation is fully independent of the Froude number. We show that this intriguing property is intimately related to the three‐dimensional nature of river bars, which allows for a gentle lateral deviation of the flow without significant deformation of the water surface. Free alternate bars are sequences of erosion and deposition areas that often appear in rivers. Their characteristic downstream movement often represents a problem for the river management, as bars can affect navigation, erode banks and affect the functioning of engineering structures. In this study, we derive and test a simple formula to predict whether free alternate bars are expected to form in a river, depending on channel geometry and flow conditions. Moreover, we provide the first complete physical explanation of their formation mechanism. Surprisingly this mechanism turns out to be extremely simple, as it essentially results from an imbalance between water weight and bottom friction, which produce flow acceleration/deceleration and sediment erosion/deposition during floods. Essential features of alternate bars can be captured by neglecting the water surface deformationFree bars formation essentially depends on an imbalance between of water weight and bottom friction, which produces flow accelerationsWe derived and tested an explicit, physically based formula for predicting the occurrence of free migrating bars in rivers Essential features of alternate bars can be captured by neglecting the water surface deformation Free bars formation essentially depends on an imbalance between of water weight and bottom friction, which produces flow accelerations We derived and tested an explicit, physically based formula for predicting the occurrence of free migrating bars in rivers

We investigated a family with a duplication, dup(X)q26–q27, that was present in two brothers, their mother, and their maternal grandmother. The brothers carrying the duplication displayed spina bifida and panhypopituitarism, whereas a third healthy brother inherited the normal X chromosome. Preferential inactivation of the X chromosome containing the duplication was evident in healthy carrier females. We determined the boundaries of the Xq26–q27 duplication. Via interphase FISH analysis we narrowed down each of the two breakpoint regions to ∼300-kb intervals. The proximal breakpoint is located in Xq26.1 between DXS1114 and HPRT and is contained in YAC yWXD599, while the distal breakpoint is located in Xq27.3 between DXS369 and DXS1200 and contained in YAC yWXD758. The duplication comprises about 13 Mb. Evidence from the literature points to a predisposing gene for spina bifida in Xq27. We hypothesize that the spina bifida in the two brothers may be due to interruption of a critical gene in the Xq27 breakpoint region. Several candidate genes were mapped to the Xq27 critical region but none was shown to be disrupted by the duplication event. Recently, M. Lagerström-Fermér et al.(1997, Am. J. Hum. Genet.60, 910–916) reported on a family with X-linked recessive panhypopituitarism associated with a duplication in Xq26; however, no details were reported on the extent of the duplication. Our study corroborates their hypothesis that X-linked recessive panhypopituitarism is likely to be caused by a gene encoding a dosage-sensitive protein involved in pituitary development. We place the putative gene between DXS1114 and DXS1200, corresponding to the interval defined by the duplication in the present family.

Migrating bars are large‐scale, alternate bedforms that often develop in channelized river reaches, as a consequence of an intrinsic instability of the erodible channel bed. Their behavior under steady flow conditions has been widely investigated by means of theoretical, experimental, and numerical models, which revealed that bar formation occurs when the width‐to‐depth ratio of the channel exceeds a critical threshold value. Conversely, no much information is available about the long‐term, average characteristics of alternate bars in the case of a complex flow regime, which makes the width‐to‐depth ratio highly variable in time. Starting from the state‐of‐the‐art theoretical models of bar dynamics, we propose a novel methodology to determine the long‐term bar response to the hydrological river regime and the associated “bar‐forming” discharge that, if applied steadily, would produce the same morphological response. We derive a generalized criterion to define whether bars are expected to form and to estimate the long‐term bar topography, depending on flow probability density function and channel characteristics (width, slope and sediment size). Our procedure differs from the classical methods to define formative discharge, inasmuch as it accounts for the specific and reversible response of bar topography to the different flow stages that compose the hydrological regime. Application to four different gravel bed reaches in the Alpine region shows the capability of the procedure to interpret remarkably different riverbed morphologies and to provide a reasonable prediction of the observed bar height, thus suggesting its potential to analyze long‐term morphological trajectories following hydrological alterations and river restoration projects. Alternate bars are large bedforms that can spontaneously develop in rivers. They often represent an issue in river management since they affect navigation, increase the flooding risk and interact with instream structures. A number of studies is available to predict the characteristics of alternate bars under constant‐discharge conditions. Conversely, the long‐term response of the average bar topography to a complex sequence of flood events is to a large extent unexplored. In this work, we propose a novel theoretically based procedure to assess whether alternate bars are expected to form in a river, to predict the average bar height, and to estimate the equivalent, bar‐forming discharge that can be effectively used in constant‐discharge models. This method may be used for evaluating the response of alternate bars to modifications of the hydrological flow regime (e.g., due to climate changes or hydropower production) or river restoration interventions (e.g., enlargement or narrowing of the channel width). We propose a theoretically based method for predicting the long‐term response of migrating bars to the hydrological regimeOur procedure allows for determining whether alternate bars are expected to form, and for predicting their average heightWe define a bar‐forming discharge that, if applied steadily, would produce the same morphology as the full hydrological regime We propose a theoretically based method for predicting the long‐term response of migrating bars to the hydrological regime Our procedure allows for determining whether alternate bars are expected to form, and for predicting their average height We define a bar‐forming discharge that, if applied steadily, would produce the same morphology as the full hydrological regime

Le syndrome d’apnées obstructives du sommeil (SAOS) est considéré un facteur de risque cardiovasculaire. La fermeture répétée des voies aériennes supérieures pendant le sommeil déclenche des phénomènes physiopathologiques responsables d’un déséquilibre sympathovagal, médiateur central des conséquences cardiovasculaires. Par contre l’effet de la CPAP sur les complications cardiovasculaires reste controversé. Une explication proposée est que l’index d’apnées-hypopnées (IAH) pourrait être insuffisant à représenter les phénomènes à l’origine des effets cardiovasculaires. Notre objectif est de tester la capacité d’une manœuvre de deep breathing(DB) à montrer une dysfonction autonomique chez des patients SAOS, en comparaison aux analyses classiques de la variabilité du rythme cardiaque (HRV).

Nickel manganite thin films were prepared by chemical solution deposition from nitrate and acetate precursors on polished alumina substrates. By variation of crystallization temperature between 650 ​°C and 900 ​°C and atmosphere during cooling of the films, the morphology, phase formation and electrical properties of the films were investigated. The electrically conductive spinel phase was formed as a main phase independent of processing conditions exhibiting NTCR characteristics. Cooling down in nitrogen atmosphere favored the decomposition of the spinel phase into nickel oxide and a spinel phase with higher manganese content, but it also reduced the resistance drift of the samples. From this finding it can be deduced that a reduced oxygen partial pressure influences defect equilibria and by that decreases cation vacancy concentration. This supports the assumption that cation redistribution by a cation vacancy diffusion mechanism is a relevant mechanism of resistance drift in such thin films.

Human Xq27 contains candidate regions for several disorders, yet is predicted to be a gene-poor cytogenetic band. We have developed a transcription map for the entire cytogenetic band to facilitate the identification of the relatively small number of expected candidate genes. Two approaches were taken to identify genes: (1) a group of 64 unique STSs that were generated during the physical mapping of the region were used in RT-PCR with RNA from human adult and fetal brain and (2) ESTs that have been broadly mapped to this region of the chromosome were finely mapped using a high-resolution yeast artificial chromosome contig. This combined approach identified four distinct regions of transcriptional activity within the Xq27 band. Among them is a region at the centromeric boundary that contains candidate regions for several rare developmental disorders (X-linked recessive hypoparathyroidism, thoracoabdominal syndrome, albinism–deafness syndrome, and Borjeson–Forssman–Lehman syndrome). Two transcriptionally active regions were identified in the center of Xq27 and include candidate regions for X-linked mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE) genes. The analysis thus suggests clustered transcription in Xq27 and provides candidates for several heritable disorders for which the causative genes have not yet been found.

Abstract: The main properties of lsquopathogenesis-relatedrsquo proteins induced inNicotiana species during hypersensitive reactions to different pathogens, as well as by chemical or physical treatments, are listed. These properties are compared with those of similar protein compounds occurring in other plant species in similar circumstances. The plants include cucumber, cowpea,Gomphrena globosa kidney bean,Gynura aurantiaca, tomato, potato, citron and celery. Similarities with other proteins normally occurring in plants, such as proteinase inhibitors, are considered. Analogies and differences with proteins induced in plants by environmental stresses, and with the lsquoantiviral factorsrsquo and the lsquoinhibitor of viral replicationrsquo occurring inNicotiana species are briefly discussed.