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Comparisons and linkage between multiple imaging scales are essential for neural circuit connectomics. Here, we report 20 new recombinant rabies virus (RV) vectors that we have developed for multi-scale and multi-modal neural circuit mapping tools. Our new RV tools for mesoscale imaging express a range of improved fluorescent proteins. Further refinements target specific neuronal subcellular locations of interest. We demonstrate the discovery power of these new tools including the detection of detailed microstructural changes of rabies-labeled neurons in aging and Alzheimer’s disease mouse models, live imaging of neuronal activities using calcium indicators, and automated measurement of infected neurons. RVs that encode GFP and ferritin as electron microscopy (EM) and fluorescence microscopy reporters are used for dual EM and mesoscale imaging. These new viral variants significantly expand the scale and power of rabies virus-mediated neural labeling and circuit mapping across multiple imaging scales in health and disease.

Background: Efforts to improve colonoscopy have recently focused on improving adenoma detection through individual interventions. We evaluated an optimized computer-assisted technique (CADopt) versus standard colonoscopy. Methods: A prospective randomized controlled trial was conducted enrolling adults (45–80 years) undergoing elective colonoscopy. Participants were randomized (1:1) to the intervention group (CADopt), and control group. In the CADopt group, endoscopists used a computer-aided polyp detection combined with linked color imaging, water exchange colonoscopy, and cecal retroflexion. In the control group, standard colonoscopy was performed. Primary outcome was Adenoma Detection Rate (ADR) in the intervention and control groups. Secondary outcomes included polyp detection rate (PDR), advanced ADR (AADR), sessile-serrated lesion detection rates (SDR), and Adenoma per colonoscopy (APC). Results: A total of 467 patients were recruited and randomized (CADopt group 229 patients, 50.2% female vs 238 patients, 48.3% female in the control group). ADR was 49.3% (95% CI 42.7–56.0) for the CADopt group vs 38.2% (95% CI 32.0–44.7) for the control group (p= 0.016). PDR, AADR, SDR, and APC were 78.2% (95% CI 72.2–83.3), 13.1% (95% CI 9.0–18.2), 6.6% (95% CI 3.7–10.6), and 0.86 (95% CI 0.70–1.02) for the CADopt group versus 59.2% (95% CI 52.7–65.5), 8.0% (95% CI 4.9–12.2), 7.1% (95% CI 4.2–11.1), and 0.75 (95% CI 0.58–0.92) for the control group, respectively. Conclusion: Using an optimized computer-assisted technique led to significant improvements in ADR, PDR, and a trend towards AADR improvements.

Colon cancer is a type of cancer in the large intestine. It is an important health problem in Canada. Colonoscopy is a medical test that uses a camera to see the inside of the large intestine. When looking in the large intestine with this camera, doctors can find and remove abnormal tissue and prevent cancer. So, colonoscopy could help doctors decrease cancer in the large intestine and its related deaths. To find abnormal tissue, you need to see the entire large intestine, from the beginning to the end. We developed a system that uses computer mathematical power to tell us if a doctor could see the entire large intestine. This can be achieved by the spotting of specific items by this system. We found that this system was good at identifying the specific items. Therefore, a doctor can be sure that he saw the entire colon, and removed all abnormal tissue. We can use this system for automatically producing reports, documenting photos of the large intestine that were taken by the camera during the colonoscopy, and improving colonoscopy quality.

Background and aims: Serrated lesions (SL) have been associated with significant risks of developing colorectal cancer (CRC). Data on synchronous findings after SL detection during colonoscopy is limited. Study aim was to evaluate the rate of synchronous advanced neoplasia (S-AN) and synchronous CRC (S-CRC) in colonoscopies where SLs were detected. Methods: We conducted a retrospective study of screening aged patients 45–74year with colorectal SL (sessile serrated polyp [SSP] or traditional serrated adenoma [TSA]) detected during an elective colonoscopy. Primary outcome was risk of S-AN in patients with SL. Secondary outcomes included risk of S-AN or S-CRC stratified by SL characteristics. Results: The study included 1262 patients with 1649 SLs (1214 with SSPs and 48 with TSAs). 47.2% were female and 22.9% of exams were screening colonoscopies, 48.2% surveillance, 28.9% diagnostic. The overall rates of S-AN and S-CRC were 15.1% and 1.3%, respectively. Presence of SSPs ≥ 10 mm was associated with higher rates of S-AN, (18.1 vs. 12.2%, Odds-Ratio [OR] = 1.61 [95% Confidence Interval [CI] 1.17–2.23], p= 0.004). SSP dysplasia was predictive of S-AN, (30.3 vs 14.1%, OR = 2.68 [95%CI 1.24–5.78], p= 0.012) but not S-CRC. SSP number (≥ 3) and location (proximal) were not predictors of S-AN or S-CRC. Conclusion: Patients with SLs are at high-risk of S-AN and S-CRC. Findings of SSPs ≥ 10 mm and SSP dysplasia are associated with high-risk of S-AN. Endoscopists should exercise heightened vigilance for synchronous findings when SLs are detected, especially SSPs ≥ 10 mm or when bowel preparation is suboptimal. Studies contrasting synchronous risk of other polyp types are needed to confirm these results.

Health care deciders are aware of the inappropriate use of proton pump inhibitors (PPIs). To reduce inappropriate prescriptions, the Conseil du Médicament (CdM) issued a practice guideline and the Régie de l’Assurance Maladie du Quebec (RAMQ) asked prescribers to justify its use by writing a specific indication code for their patients to obtain drug coverage.

L’hyperparathyroïdie primaire (HPT1re) est une pathologie fréquente chez le sujet âgé, et représente un surrisque de fracture et d’aggravation des comorbidités. La chirurgie est le traitement de première intention mais elle n’est pas consensuelle chez le sujet âgé. Quel est l’état des pratiques dans cette population ?

The newly democratizing Eastern European nations are faced with a three-fold task of introducing a stabilization process, implementing structural reform, and maintaining political credibility. Structural reforms are dependent on the economic restructuring which, in turn, is dependent on the governments' political credibility. An overview of investment opportunities and the associated risks of the Eastern European nations is presented. Investment and ownership legislation, political risk of new economic policies, and profit repatriation policies are covered. Hungary offers the most attractive market for foreign investment, but compared to the developing nation of Tunisia, it still has not achieved economic stability. However, the higher education level of Hungarian labor gives Hungary an advantage over developing nations as a site for foreign investment.

Laboratory flow tests performed on granular materials in rigid-wall permeameters are used to determine the hydraulic conductivity of saturated materials or to study particle migration. For such tests, specimen preparation is important, particularly the saturation process. The presence of gas bubbles in the tested specimen leads to smaller hydraulic conductivity values and may affect particle migration. Therefore, measures must be taken to obtain fully saturated specimens. In order to improve saturation, two elements have to be taken into consideration: first, the presence of gas in the permeant water; second, the presence of gas in the pores of the specimen. Several flow tests are described in ASTM standards. These standards involve different conditioning methods for permeant water (e.g., heating, seepage through a sand filter, cavitation under vacuum), and different specimen saturation methods (e.g., saturation with an upward flow under vacuum, following carbon dioxide flushing). In this article, water deaeration and specimen saturation methods were evaluated and compared using a mass-volume method. In the first phase, the importance of using deaerated permeant water was examined by comparing different conditioning methods for permeant water. Saturation using water in equilibrium with atmospheric pressure was compared with saturation with water heated at 40°C, water deaerated using a sand filter, and water deaerated by cavitation under vacuum. In the second phase, the influence of purging the gas contained in the soil specimen before saturation using carbon dioxide or a vacuum was compared. In both cases, the permeant water was deaerated by cavitation under vacuum. These tests showed that combining a purge of the specimen with carbon dioxide with saturation using an upward flow of water deaerated by cavitation under vacuum yielded the highest degree of saturation for granular specimens in a rigid-wall permeameter. Another advantage of this combination is that it accelerates specimen saturation.

Turbulent fluxes at the air‐sea interface are estimated with data collected in 2011 to 2017 with a low‐profile platform during six experiments in four regions. The observations were carried out with moderate winds (2–10 m/s) and averaged wave heights of 1.5 m. Most of the time, there was a swell, with an averaged wave age (the ratio between wave phase speed and wind speed) being equal to 2.8 ± 1.6. Three flux calculation methods are used, namely, the eddy covariance (EC), the inertial dissipation (ID), and the bulk methods. For the EC method, a spectral technique is proposed to correct wind data from platform motion. A mean bias affecting the friction velocity (u*) is then evaluated. The comparison between EC u*and ID u*estimates suggests that a constant imbalance term (ϕimb) equal to 0.4 is required in the ID method, possibly due to wave influence on our data. Overall, the confidence in the calculated u*estimates is found to be on the order of 10%. The values of the drag coefficient (CD) are in good agreement with the parameterizations of Smith (1988, https://doi.org/10.1029/JC093iC12p15467) in medium‐range winds and of Edson et al. (2013, https://doi.org/10.1175/JPO‐D‐12‐0173.1) in light winds. According to our data, the inverse wave age varies linearly with wind speed, as in Edson et al. (2013, https://doi.org/10.1175/JPO‐D‐12‐0173.1), but our estimates of the Charnock coefficient do not increase with wind speed, which is possibly related to sampling swell‐dominated seas. We find that the Stanton number is independent from wind speed. A small wave‐following platform was deployed in 2011–2017 across four oceanic regions. The data are used to estimate turbulent fluxes, which are physical quantities that describe the exchanges of heat and momentum through the air‐sea interface. In weather models, simplified representations of the fluxes are used, which themselves depend on coefficients named drag coefficient for momentum exchange and Stanton number for temperature exchange, respectively. In this study, we evaluate these coefficients. First, we compare the flux estimates from the three main available methods. We adjust the parameters in the methods to reach the best possible agreement between the calculated fluxes. Two types of corrections are proposed, depending on the method considered, because turbulence data are modified by the motion of the platform and by the proximity of waves. Data are corrected by applying a mean bias to the fluxes and by accounting for a nonmeasured term in the turbulence equations. Then, we analyze the wind dependence of the estimated drag coefficient and Stanton number. We find that drag is slowly increasing with wind speed, in agreement with existing models. Estimates of the Stanton number have biases but which do not depend on wind speed. The drag coefficient at the air‐sea interface follows Smith (1988) in moderate winds and hardly increases in light windsA constant imbalance term of 0.4 is required in the inertial dissipation flux calculation method, with data sampled at a 1.5‐m heightStanton number estimates are independent from wind speed in moderate winds

Supplemental Digital Content is available in the text.

Inflammatory bowel diseases are associated with dysregulated immune responses in the intestinal tissue. Four molecularly identified macrophage subsets control immune homeostasis in healthy gut. However, the specific roles and transcriptomic profiles of the phenotypically heterogeneous CD14+macrophage-like population in inflamed gut remain to be investigated in Crohn’s disease (CD). Here we identified two phenotypically, morphologically and functionally distinct colonic HLADR+SIRPα+CD14+subpopulations that were further characterized using single-cell RNA-sequencing (scRNAseq) in CD. Frequencies of CD64hiCD163−/dimcells selectively augmented in inflamed colon and correlated with endoscopic score of disease severity. IL-1β and IL-23-producing CD64hiCD163−/dimcells predominated over TNF-α-producing CD64hiCD163hicells in lesions. Purified “inflammatory monocyte-like” CD163−, but not “macrophage-like” CD163hicells, through IL-1β, promoted Th17/Th1 but not Th1 responses in tissue memory CD4+T cells. Unsupervised scRNAseq analysis that captures the entire HLADR+SIRPα+population revealed six clusters, two of which were enriched in either CD163−or CD163hicells, and best defined by TREM1/FCAR/FCN1/IL1RNor CD209/MERTK/MRCI/CD163L1genes, respectively. Selected newly identified discriminating markers were used beyond CD163 to isolate cells that shared pro-Th17/Th1 function with CD163−cells. In conclusion, a molecularly distinct pro-inflammatory CD14+subpopulation accumulates in inflamed colon, drives intestinal inflammatory T-cell responses, and thus, might contribute to CD disease severity.

Background: Fiber supplementation during enteral nutrition has been recommended, but the effect of soluble compared with insoluble fiber supplements on antroduodenal motility is unknown. Objective: The objective of this study was to compare antroduodenal motor patterns in 8 healthy volunteers during and after gastric infusion of 3 different diets: a fiber-free diet, an insoluble-fiber diet, and a mixed-fiber diet (50% soluble fiber and 50% insoluble fiber). Design: Manometric studies with the 3 different diets (2100 kJ) were performed in random order. Antroduodenal motility was monitored continuously for 6 h by using a pneumohydraulic system to calculate the number, amplitude, and duration of the pressure waves; the area under the curve (AUC); and the percentage of time occupied by motor activity before, during, and after each type of infusion. Variations in antral areas were measured by ultrasonography. Results: The gastric motor response was significantly higher, whatever the diet, in the distal antral recording site than in the 2 more proximal sites. In the proximal but not the distal antrum, the number of waves, the AUC, and the percentage of time occupied by motor activity were higher (P [is less than] 0.04) with the mixed-fiber than with the insoluble-fiber diet. No significant differences in variations of antral area were observed among the 3 diets. In the duodenum, motor variables were not significantly different among the 3 diets. Conclusions: A gastric infusion induced a greater motor response in the distal than in the proximal antrum. A mixed-fiber diet was associated with significantly greater proximal antral motility than was an insoluble-fiber diet. There was no significant difference among the 3 formulas in duodenal motor variables or in variations in antral area as measured by ultrasound. Am J Clin Nutr 2000;72:1040-6. KEY WORDS Enteral nutrition, antroduodenal motility, ultrasound gastric emptying, dietary fiber, healthy volunteers

During winter 2012–2013, open-ocean deep convection which is a major driver for the thermohaline circulation and ventilation of the ocean, occurred in the Gulf of Lions (Northwestern Mediterranean Sea) and has been thoroughly documented thanks in particular to the deployment of several gliders, Argo profiling floats, several dedicated ship cruises, and a mooring array during a period of about a year. Thanks to these intense observational efforts, we show that deep convection reached the bottom in winter early in February 2013 in a area of maximum 28?±?3 109m2. We present new quantitative results with estimates of heat and salt content at the subbasin scale at different time scales (on the seasonal scale to a 10 days basis) through optimal interpolation techniques, and robust estimates of the deep water formation rate of 2.0 ±0.2?Sv. We provide an overview of the spatiotemporal coverage that has been reached throughout the seasons this year and we highlight some results based on data analysis and numerical modeling that are presented in this special issue. They concern key circulation features for the deep convection and the subsequent bloom such as Submesoscale Coherent Vortices (SCVs), the plumes, and symmetric instability at the edge of the deep convection area. We study deep convection and subsequent bloom in the northwestern Mediterranean Sea based on modern observation techniquesWe provide estimates of mass and energy fluxes over a period of a year in the deep convection area and deep water formation ratesWe highlight small-scale circulation features that are important for deep convection and subsequent bloom and introduce this special issue

Notre objectif était d’évaluer les performances de la TEP/TDM au 18FDG dans les cancers différenciés thyroïdiens agressifs et son impact thérapeutique.

The north‐western Mediterranean Sea is a key location for the thermohaline circulation of the basin. The area is characterized by intense air‐sea exchanges favored by the succession of strong northerly and north‐westerly wind situations (mistral and tramontane) in autumn and winter. Such meteorological conditions lead to significant evaporation and ocean heat loss that are well known as the main triggering factor for the Dense Water Formation (DWF) and winter deep convection episodes. During the HyMeX second field campaign (SOP2, 1 February to 15 March 2013), several platforms were deployed in the area in order to document the DWF and the ocean deep convection, as the air‐sea interface conditions. This study investigates the role of the ocean‐atmosphere coupling on DWF during winter 2012–2013. The coupled system, based on the NEMO‐WMED36 ocean model (1/36° resolution) and the AROME‐WMED atmospheric model (2.5 km resolution), was run during 2 months covering the SOP2 and is compared to an ocean‐only simulation forced by AROME‐WMED real‐time forecasts and to observations collected in the north‐western Mediterranean area during the HyMeX SOP2. The comparison shows small differences in terms of net heat, water, and momentum fluxes. On average, DWF is slightly sensitive to air‐sea coupling. However, fine‐scale ocean processes, such as shelf DWF and export or eddies and fronts at the rim of the convective patch, are significantly modified. The wind‐current interactions constitute an efficient coupled process at fine scale, acting as a turbulence propagating vectors, producing large mixing and convection at the rim of the convective patch. The AROME‐NEMO WMED coupled model was run over HyMeX SOP2 and compared to a uncoupled ocean simulation validated against observationsAir‐sea coupling induces small differences in surface fluxes and in dense water formation (chronology, characteristics, and volumes)Fine‐scale ocean structures around and interacting with the convective patch are the most sensitive to the air‐sea coupling

Ces dix dernières années, le nombre annuel de morts inattendues du nourrisson stagne à 230 cas, et l’on estime que le tiers serait évitable si les conditions de couchages étaient conformes aux recommandations de prévention de la MIN. L’objectif principal de cette étude était de faire un état des lieux des représentations du couchage des nourrissons au sein des magazines et sites destinés aux parents, selon les recommandations de prévention de la MIN.

Fusion of catalytic domains can accelerate cascade reactions by bringing enzymes in close proximity. However, the design of a protein fusion and the choice of a linker are often challenging and lack of guidance. To determine the impact of linker parameters on fusion proteins, a library of linkers featuring various lengths, secondary structures, extensions and hydrophobicities was designed. Linkers were used to fuse the lycopene cyclase (crtY) and β-carotene hydroxylase (crtZ) from Pantoea ananatisto create fusion proteins to produce zeaxanthin. The fusion efficiency was assessed by comparing the carotenoids content in a carotenoid-producer Escherichia colistrain. It was shown that in addition to the orientation of the enzymes and the size of the linker, the first amino acid of the linker is also a key factor in determining the efficiency of a protein fusion. The wide range of sequence diversity in our linker library enables the fine tuning of protein fusion and this approach can be easily transferred to other enzyme couples.

Satellite observations of significant wave height (Hs) have recently reached 30 years of continuous record. Is this length sufficient to detect the effect of anthropogenically forced climate change on wave height trends? Wave height decadal variability is influenced by a combination of internal variability and forced variability caused by both anthropogenic and natural forcing. Using a statistical model to derive Hsfrom sea level pressure field and exploiting ERA‐5 reanalysis data as well as 80 members of the Community Earth System Model v2 large ensemble, we show that, over the North Atlantic (NA), altimetry‐based Hstrends are mostly caused by internal variability. This suggests that Hschanges computed over the satellite era are not yet controlled by anthropogenic climate change. Starting from 1993, the date of emergence, defined as the date when the forced signal becomes dominant over the internal variability, is later than 2050 for Hsin the NA. Satellite observations of significant wave height will soon reach 30 years of continuous record. Changes in significant wave height over this period can either be attributed to both anthropogenic or “natural” climate forcing or to the intrinsic variability of the climate system. In this article, we show that the intrinsic variability effect largely dominates the significant wave height changes in the North Atlantic (NA) over the 30 years of satellite observations. We further estimate that the significant wave height changes associated with anthropogenically forced climate change will become dominant over those due to the intrinsic variability after 2050 in most of the NA region. Altimeter based significant wave height trends in the North Atlantic (NA) are largely dominated by internal variabilityForced significant wave height changes in the NA will only be detectable in altimeter data after 2050 Altimeter based significant wave height trends in the North Atlantic (NA) are largely dominated by internal variability Forced significant wave height changes in the NA will only be detectable in altimeter data after 2050

We present here a unique oceanographic and meteorological data set focus on the deep convection processes. Our results are essentially based on in situ data (mooring, research vessel, glider, and profiling float) collected from a multiplatform and integrated monitoring system (MOOSE: Mediterranean Ocean Observing System on Environment), which monitored continuously the northwestern Mediterranean Sea since 2007, and in particular high‐frequency potential temperature, salinity, and current measurements from the mooring LION located within the convection region. From 2009 to 2013, the mixed layer depth reaches the seabed, at a depth of 2330m, in February. Then, the violent vertical mixing of the whole water column lasts between 9 and 12 days setting up the characteristics of the newly formed deep water. Each deep convection winter formed a new warmer and saltier “vintage” of deep water. These sudden inputs of salt and heat in the deep ocean are responsible for trends in salinity (3.3 ± 0.2 × 10−3/yr) and potential temperature (3.2 ± 0.5 × 10−3C/yr) observed from 2009 to 2013 for the 600–2300 m layer. For the first time, the overlapping of the three “phases” of deep convection can be observed, with secondary vertical mixing events (2–4 days) after the beginning of the restratification phase, and the restratification/spreading phase still active at the beginning of the following deep convection event. Continuous monitoring of five consecutive winters of deep convection that reached the seabed, found at a depth of 2300 mObservation of the overlapping of the deep convection phases (vertical mixing/restratification; spreading/preconditioning)Formation of warmer and saltier new deep water mass “vintages” after each event of deep convection

The north‐western Mediterranean Sea is a key location where intense air‐sea exchanges occur in autumn and winter. The succession of strong mistral and tramontane situations, leading to significant evaporation and ocean heat loss, is well known as the controlling factor in the dense water formation (DWF) with deep convection episodes. During HyMeX‐SOP2 (1 February to 15 March 2013), several platforms sampled the area in order to document DWF and air‐sea exchanges. This study investigates the ability of the NEMO‐WMED36 ocean model (1/36°‐resolution), driven in surface by the hourly air‐sea fluxes from the AROME‐WMED forecasts (2.5 km resolution), to represent DWF during HyMeX‐SOP2 and focuses on the sensitivity to initial conditions. After a short evaluation of the atmospheric forcing, the high‐resolution oceanic simulations using three different data sets as initial and boundary conditions are compared to observations collected during the field campaign. It evidences that using regional model outputs may lead to unrealistic thermohaline characteristics for the intermediate and deep waters, which degrade the simulated new dense water formed. Using ocean analyses built from observations, permits to obtain more realistic characteristics of the Western Mediterranean dense water. However, a low stratification favors an overestimation of the convective area and of the DWF rate. The DWF chronology is also impacted. Nevertheless, in every run, SOP2 is characterized by the production of water denser than 29.11 kg m−3with a peak during the strong mistral event of 23–25 February followed by a period of restratification, before a last event of bottom convection on 13–15 March. Three high‐resolution ocean simulations are compared to HyMeX SOP2 observationsThe NEMO‐WMED36 model is able to reproduce dense water formation during winter 2013.The large sensitivity of dense water formation to initial conditions is highlighted

The evolution of the stratification of the north‐western Mediterranean between summer 2012 and the end of winter 2013 was simulated and compared with different sets of observations. A summer cruise and profiler observations were used to improve the initial conditions of the simulation. This improvement was crucial to simulate winter convection. Variations of some parameters involved in air ‐ sea exchanges (wind, coefficient of transfer used in the latent heat flux formulation, and constant additive heat flux) showed that the characteristics of water masses and the volume of dense water formed during convection cannot be simply related to the time‐integrated buoyancy budget over the autumn ‐ winter period. The volume of dense water formed in winter was estimated to be about 50,000 km3with a density anomaly larger than 29.113 kg m−3. The effect of advection and air/sea fluxes on the heat and salt budget of the convection zone was quantified during the preconditioning phase and the mixing period. Destratification of the surface layer in autumn occurs through an interaction of surface and Ekman buoyancy fluxes associated with displacements of the North Balearic front bounding the convection zone to the south. During winter convection, advection stratifies the convection zone: from December to March, the absolute value of advection represents 58 % of the effect of surface buoyancy fluxes. Realistic simulation of winter convection and dense water formationCorrection of initial and boundary conditions improves the simulationSensitivity studies to air ‐ sea fluxes are characterized

Impaired growth has been reported in children born with esophageal atresia (EA). Their nutritional fate at adulthood remains uncertain though. Our objectives were to determine the body mass index (BMI) of adult patients with EA followed up from 2009 to 2011 in the EA clinic of a university-affiliated hospital in Quebec (Canada), and investigate characteristics associated with underweight. The 40 adult patients with EA attending the clinic were invited to participate. Height and weight were measured and BMI calculated. Patients with BMI < 18.5 kg/m2were deemed underweight. Patients’ characteristics were obtained, including digestive symptoms and compensatory eating behaviors. Nonparametric tests were used to compare the proportion of underweight among patients with EA with that found in the Quebec population and the characteristics between patients with EA deemed underweight and those with BMI = 18.5 kg/m2. The final sample included 16 women and 21 men, ages 18 to 44 years. Mean BMI was 21.3 ± 4.9 kg/m2and 24.3% had BMI < 18.5 kg/m2, which is higher than in the Quebec adult population (2.5%, P< 0.001). Compared with patients with EA having BMI = 18.5 kg/m2, underweight patients had more often experienced failure to thrive during their adolescence (55.6% vs 7.4%, P= 0.006), and reported severe postprandial fullness (62.5% vs 21.4%, P= 0.040), the need to eat slowly (87.5% vs 46.4%; P= 0.045), and severe difficulties to swallow dry solid foods (50.0% vs 14.3%, P= 0.054). Insufficient body weight is prevalent in this sample of adult patients with EA and could result from digestive symptoms. Follow-up with a gastroenterologist and nutritional counseling should be considered for adult patients with EA.

ABSTRACTThe microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that Helicobacter pyloriseropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of H. pylorion outcomes and microbiome composition. We performed H. pyloriserology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pyloripositive (Pos). H. pyloriPos patients had a significantly shorter overall survival (p = .02) compared to H. pylorinegative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pyloriPos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylorigroups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques, and Dorea formicigeneranswere increased in the H. pyloriPos group, while Alistipes finegoldii, Hungatella hathewayiand Blautia productawere over-represented in the H. pyloriNeg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvenswas increased in H. pyloriNeg patients. Our results demonstrated that the negative impact of H. pylorion outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pyloriin immuno-oncology arena.

Déterminer les motivations poussant les femmes enceintes à utiliser Internet, leurs habitudes vis-à-vis de ce média, ainsi que les sujets d’informations recherchés. Nous avons aussi cherché à établir le profil des femmes enceintes utilisatrices d’Internet afin de pouvoir mieux appréhender et comprendre l’impact de ce média sur le vécu, les comportements et les prises de décisions de ces femmes vis-à-vis de leur grossesse.

Background Over the last decade, biologics have gained an important place for the treatment of moderate to severe inflammatory bowel disease (IBD), and many randomized control trials have evaluated their efficacy.Aim The goal of this review is to analyze the results of these trials and to highlight the evidence and indications emerging from these studies for their implementation in the management of IBD patients.Methods A PubMed search was realized to screen high-quality clinical trials studying biologic agents currently available in clinics for the treatment of IBD. Words used were: “infliximab,” “adalimumab,” “certolizumab,” “golimumab,” “natalizumab,” “vedolizumab,” “ustekinumab,” “azathioprine,” “methotrexate,” “Crohn's disease,” and “ulcerative colitis.”Results In Crohn's disease, studies supporting induction and maintenance therapies were documented for infliximab, adalimumab, certolizumab, natalizumab, vedolizumab, and ustekinumab. Infliximab, adalimumab, and certolizumab have evidences for fistulizing Crohn's disease and only infliximab and adalimumab have evidences for mucosal healing. In ulcerative colitis, studies supporting induction, maintenance, and mucosal healing were found with infliximab, adalimumab, golimumab, and vedolizumab. Only infliximab was associated with evidences for combination therapy with thiopurine and acute severe colitis in ulcerative colitis.Conclusion Management with biologics in IBD patients is well validated by high-quality clinical trials.

Much effort has been devoted to determining how cellular and noncellular components of the tumoral niche initiate and promote cancer development. Cancer cells perceive biochemical signals from components of the extracellular matrix (ECM) and sense physical features, such as matrix stiffness and cell confinement. The past decade has seen a better understanding of the biophysics and mechanobiology associated with cancer cells. Indeed, loss of mechanisms controlling the production, the degradation, and the remodeling of ECM contributes to tumor growth or cell dissemination by affecting cell contractility in response to ECM stiffness and by stimulating mechanical dependence of growth factor activation.

Tide gauge records are the primary source of sea level information over multidecadal to century timescales. A critical issue in using this type of data to determine global climate‐related contributions to sea level change concerns the vertical motion of the land upon which the gauges are grounded. Here we use observations from the Global Positioning System for the correction of this vertical land motion. As a result, the spatial coherence in the rates of sea level change during the twentieth century is highlighted at the local and the regional scales, ultimately revealing a clearly distinct behavior between the Northern and the Southern Hemispheres with values of 2.0 mm/yr and 1.1 mm/yr, respectively. Our findings challenge the widely accepted value of global sea level rise for the twentieth century. Detection of a spatial pattern between hemispheres in secular sea level ratesUse of most advanced methods and data for studying secular trends in sea levelVertical land motion: An obstacle to detecting fingerprints in sea level change

ABSTRACTDiarrhea is a frequent complication after kidney transplantation, ascribed to adverse effects of the immunosuppressive therapy in case of negative microbiological examination of the stools. The aim of this study was to improve the microbiological diagnosis by implementing molecular tests. Fifty-four severe diarrhea events that occurred in 49 adult kidney transplant recipients from September 2010 to November 2011 were investigated. One or several enteric pathogens were detected in 13 (23%) stool samples using classical microbiological methods versus 39 (72%) for the seven commercially available multiplex PCR assays used retrospectively (P= 0.006). Interestingly, molecular diagnosis identified 15 multiple infections compared to none using classical techniques. The primary pathogens detected were enteropathogenic Escherichia coli(EPEC) (n= 15; 38%), Campylobacterspp. (n= 15; 38%), and Norovirus(n= 14; 36%). Specificities for Campylobacterand Norovirusinfection diagnosis were 75 and 100%, respectively, by comparison to reference methods. Based on molecular findings, a cyclosporine-mycophenolate mofetil combination was identified as a risk factor for developing Norovirus-induced diarrhea. Norovirusinfections were also responsible for higher weight loss than all the other causes of diarrhea. In samples from asymptomatic immunocompromised and immunocompetent patients, EPEC but not Norovirusand Campylobacterinfections were detected at a frequency similar to that observed in symptomatic kidney transplant recipients. In conclusion, molecular tools significantly improved the detection of single and multiple enteric infections by comparison to classical techniques and could quickly become the key element in the management of severe acute diarrhea in transplant recipients.

ABSTRACTEnterovirus 68 was detected in 10 respiratory specimens from pediatric patients hospitalized for acute wheezing or bronchitis during 2009 in the northeast of France. Viral loads ranged from 2 × 105to 7.2 × 107copies/ml. Alignment of 5' nontranslated regions and phylogenetic analysis of partial VP1 gene sequences show that these viruses clustered and belonged to clade C.

AbstractEsophageal cancer most commonly presents with upper digestive symptoms such as dysphagia. Lymph nodes are among the most common metastatic sites of this type of cancer. We report the case of a 53-year-old man presenting with unusual sole presenting features of esophageal cancer. The patient sought medical attention for abdominal pain without dysphagia, which was first investigated with an abdominal computed tomography scan. A large abdominal mass was discovered on imaging. Biopsies of this mass were in keeping with esophageal squamous cell cancer. With this finding, gastroscopy was performed, confirming the presence of primary esophageal cancer. This is a rare presentation of esophageal cancer without upper gastrointestinal symptoms. This case reinforces the value of biopsy for any neoplastic mass, especially in a context of unusual symptoms.Copyright © 2012 S. Karger AG, Basel

Une innovation majeure est apportée par l’utilisation de gyroscopes laser. PARALIGN®est le premier appareil au monde à utiliser cette technique, appelée mesure par inertie, permettant de calculer précisément la position relative des rouleaux dans l’espace, sans visée optique, sans ligne laser à installer le long de la machine.

In this work, we have evaluated the potential of image fusion and attenuation correction (AC) of SPECT-CT imaging for the assessment of gastro-entero-pancreatic endocrine tumors by somatostatin receptor scintigraphy (SRS).MethodAfter optimisation of acquisition and reconstruction parameters, we have evaluated, in a prospective study, SRS performed over a period of one year. We have compared visual interpretations of planar and tomographic images versus SPECT/CT images to determine if anatomical localisation and diagnostic contributions are improved. In a semi-quantitative analysis of pathological foci, we have measured maximal intensity values (Tmax), tumour to background ratios (T/B) and tumour contrasts (Ct) with and without AC.ResultsIn 25 SRS, visual analysis has shown anatomical localisation improvements in 60% of cases (CI95%, 39–79) and diagnostic improvements in 64% of cases (CI95%, 43–82). Doubtful foci proportion changed from 44 to 11%. In the semi-quantitative analysis of 41 pathological foci, Wilcoxon matched-pairs tests showed significantly higher Tmax, T/B and Ct values after AC.ConclusionSPECT/CT imaging improves diagnostic quality of SRS thanks to a better foci localisation and a better lesional contrast in the image.

A breakthrough innovation is introduced through the use of laser gyroscope. PARALIGN?is the first equipment worldwide that uses this technology, referred to as inertial measurement, that makes it possible to assess the relative spatial position of rolls, without any optical alignment or laser line installed along the equipment.

Nitric oxide (NO) plays an important role as a nonadrenergic, noncholinergic inhibitory neurotransmitter in the GI tract. Our study aims were to investigate the effect of a single intragastric L-arginine (L-Arg) administration, as a source of NO, on proximal stomach tone in basal and postintragastric administration of a polymeric diet in humans and to evaluate concomitantly the effect on antral area as an indirect assessment of gastric emptying. Eight healthy volunteers were studied in a randomized double-blind crossover study after, respectively, 15 g L-Arg, 30 g L-Arg, or placebo administered in the stomach through a gastric tube. The drug administration was followed by a polymeric diet infusion (500 ml/500 kcal) at a rate of 250 ml/hr. Gastric tone variations were recorded with an electronic barostat, gastric emptying was concomitantly estimated by repeated ultrasound measurements of antral area, and symptoms were recorded throughout the experiment.

The ability of the pathogenic fungus Candida albicans to switch from a yeast to a hyphal morphology in response to external signals is implicated in its pathogenicity. We used glass DNA microarrays to investigate the transcription profiles of 6333 predicted ORFs in cells undergoing this transition and their responses to changes in temperature and culture medium. We have identified several genes whose transcriptional profiles are similar to those of known virulence factors that are modulated by the switch to hyphal growth caused by addition of serum and a 37 degrees C growth temperature. Time course analysis of this transition identified transcripts that are induced before germ tube initiation and shut off later in the developmental process. A strain deleted for the Efg1p and Cph1p transcription factors is defective in hyphae formation, and its response to serum and increased temperature is almost identical to the response of a wild-type strain grown at 37 degrees C in the absence of serum. Thus Efg1p and Cph1p are needed for the activation of the transcriptional program that is induced by the presence of serum.

The ability of the pathogenic fungus Candida albicansto switch from a yeast to a hyphal morphology in response to external signals is implicated in its pathogenicity. We used glass DNA microarrays to investigate the transcription profiles of 6333 predicted ORFs in cells undergoing this transition and their responses to changes in temperature and culture medium. We have identified several genes whose transcriptional profiles are similar to those of known virulence factors that are modulated by the switch to hyphal growth caused by addition of serum and a 37°C growth temperature. Time course analysis of this transition identified transcripts that are induced before germ tube initiation and shut off later in the developmental process. A strain deleted for the Efg1p and Cph1p transcription factors is defective in hyphae formation, and its response to serum and increased temperature is almost identical to the response of a wild-type strain grown at 37°C in the absence of serum. Thus Efg1p and Cph1p are needed for the activation of the transcriptional program that is induced by the presence of serum.

Background & Aims:Visceral hypersensitivity was detected in patients with functional gastrointestinal disorders and has been proposed as a biological marker of irritable bowel syndrome (IBS). The purpose of this study was to assess the sensitivity, specificity, and the predictive values of pain thresholds evaluated by rectal distention using an electronic barostat in patients with or without IBS and in control subjects. Methods:Patients were diagnosed according to Rome II criteria. Rectal sensory thresholds were determined in 164 patients (86 IBS patients, 26 painless constipation, 21 functional dyspepsia, and 31 miscellaneous conditions) and in 25 normal controls. All subjects underwent a series of rectal isobaric distentions using an electronic barostat. The bag was progressively distended from 0 to 48 mm Hg and, in response to distention, subjects reported on discomfort or pain. Results:Pain thresholds were lower in IBS patients (30.4 ± 6.7 mm Hg) compared with controls (44.5 ± 5), painless constipated (45.4 ± 5.3), functional dyspepsia (39.4 ± 7.8), and miscellaneous patients (43.2 ± 5.5). At the level of 40 mm Hg, the sensitivity of the rectal barostat to identify IBS patients from normal subjects and non-IBS patients was 95.5% and its specificity was 71.8%. The positive predictive value was 85.4%. The negative predictive value was 90.2%. Conclusions:Lowered rectal pain threshold is a hallmark of IBS patients. Rectal barostat testing is useful to confirm the diagnosis of IBS and to discriminate IBS from other causes of abdominal pain.

Functional gastrointestinal disorders (FGID) can benefit from various psychological interventions. The main objective here was to define the contribution of a new psychotherapeutic intervention, group counseling psychotherapy, for the management of FGID patients. Secondary aims included validation of new measures for gastrointestinal symptoms and quality of life in patients with FGID. Fifty patients seen in a tertiary care center were included in a program of 10 weekly sessions of 2 hr each. Gastrointestinal symptoms, quality of life, and psychological conditions were measured before and after treatment by quantitative indices and by qualitative self-analysis. Gastrointestinal index and quality-of-life index were significantly (P < 0.02)improved at the end of the psychotherapeutic intervention (from 77.5 ± 4.0 to 63.2 ± 4.3 and from 67.7 ± 3.9 to 54.9 ± 3.9, respectively). In a control group of patients observed for a comparable period of time while waiting for the psychotherapy program, gastrointestinal and quality of life indices remained unchanged. The severity of gastrointestinal symptoms and the quality of life deterioration were highly correlated factors (r = 0.8)at entry into the trial, and their improvement with psychotherapy was also correlated (r = 0.6; P < 0.001). Psychological abnormalities were frequent in these patients (anxiety in 31%, somatization in 29%, depression in 26% of the patients). However, no specific disorder could predict the results of the psychotherapeutic intervention. Over the long term (6–24 months after conclusion of treatment), gastrointestinal status, quality of life, and psychological condition were estimated as improved by 53%, 63%, and 67% of the patients, respectively. The gastrointestinal index and quality of life index we developed were validated to detect the disease and to follow its evolution in response to treatment. In conclusion, group counseling psychotherapy offered a significant contribution for the management, improving gastrointestinal symptoms and quality of life, of FGID patients. New measures for symptom severity and quality of life are available.

Visceral hypersensitivity was shown in patients with functional gastrointestinal disorders (FGID). The mechanisms underlying this sensory dysfunction remain undetermined. The initial hypothesis of a generalized reduction in pain tolerance was rejected by further studies that suggested a normal tolerance to somatic stimuli and led to the generally accepted assumption that pain intolerance is specific and exclusive for visceral stimuli in these patients. We wanted to revisit this theory by examining whether patients with FGID reported perception and tolerance to somatic pain differently from normal subjects and whether the response to somatic pain stimulus was correlated to gastrointestinal symptoms or psychological status or distress. Thirty-three patients with FGID (Rome II criteria)(F/M: 26/7; mean age 48 ± 9.9) and 33 normal controls (F/M: 24/9; mean age 44.1 ± 6.8) were asked to immerse their nondominant hand into 4°C water for as long as possible (maximum 120 sec). Time before appearance of: (1) discomfort, (2) pain, and (3) withdrawing of the hand were noted. The intensity of pain was rated on a visual analog scale from 0 to 100. Self-report questionnaires were used to assess the severity of gastrointestinal symptoms (St-Luc GI index) and the psychological distress (SCL-90) in the patient group. Data are expressed in seconds as mean ± sem. Discomfort sensory thresholds were similar in controls and FGID patients (28 ± 3 and 24 ± 2, respectively; NS) whereas pain and withdrawing were significantly lower in FGID (41 ± 3 and 76 ± 6 sec) than in controls (62 ± 6 and 102 ± 4; P < 0.05). Pain intensity was similar in both groups (64 ± 4 vs 67 ± 3; NS). Female patients showed lower sensory thresholds than male patients and control females (pain thresholds: 39.8 ± 3.4 vs 67.8 ± 16.7 and vs 56.8 ± 8.7; P < 0.05). Sensory thresholds were not different in subgroups of patients with FGID (irritable bowel syndrome and functional dyspepsia). No correlation was shown between sensory thresholds and gastrointestinal index or SCL 90-test. In conclusion, FGID patients showed a threshold to painful somatic stimulus that was lower than in normal subjects. These findings suggest that patients with FGID may have hyperalgesia and low pain tolerance that is not limited to the viscera, but that is part of a systemic general condition.

Background & Aims:Fibre-supplements in enteral feeding could increase the risk of gastro-oesophageal reflux (GOR). The aim of this study was to assess in humans the physiological effects of the supplementation of the enteral diet with different types of dietary fibre on gastro-oesophageal reflux episodes, gastric acidity and gastric emptying.Methods:pH profiles were compared in 12 healthy volunteers between three different formula (500 kcal, 250 mL.h-1) delivered in a random order and containing either no fibre, either soy polysaccharide fibre only or mixed fibre from pea and inuline. Enteral diets were instilled through a nasogastric tube. Oesophageal and gastric pH recordings were combined with the ultrasound measurement of gastric antral area during the infusion. Results:More GOR were observed with a fibre-free diet (median 4, range 1–10) than with a mixed (median 1.5, range 0–5) (P=0.04) or soy polysaccharide fibre (median 1.5, range 0–5) (P=0.04) diet. The median duration of GOR was longer with the mixed fibre (median 3.6, range 1.8–7.2) than with the fibre-free diet (mean 1.8 min, range 1–3.6) (P<0.05). The number of GOR episodes lasting more than 5 min, the duration of the longest GOR and the percent of time under pH 4 were not significantly different with the three diets. The intragastric pH profile and the ultrasound antral area were not different with all three diets.Conclusions:Addition of fibre to the enteral formula had limited effects on the onset of GOR episodes. It decreased the number of GOR but increased their duration. These effect were more pronounced with the formula containing soluble fibre. At variance, the addition of fibre had no significant effect on gastric emptying and gastric acid secretion.

The objectives of this study were to examine the morphology, restenosis, dilatation, and possible complications of polyester collagen impregnated carotid patches. Between March 1994 and January 1995, 207 patients (56 females and 151 males) undergoing 221 carotid endarterectomies (CE) with a collagen-impregnated knitted polyester patch were enrolled in a European prospective multicenter study. Patches were used for arteries deemed to be smaller than usual by visual inspection. General anesthesia was used in 201 procedures (91%), and a shunt was used in 76 procedures (34.4%). One hundred fourteen CE (51.6%) were checked by a perioperative arteriography or angioscopy. The diameter of the internal carotid artery (ICA) and carotid bulb (CB) were measured by duplex scan both preoperatively and every 6 months during follow-up. The main end point was carotid occlusion or restenosis, defined as a stenosis of 50% or more according to NASCET criteria. Carotid polyester-impregnated patches appear to be reliable. The patch was easy to cut and suture, and hemostasis was obtained immediately. No rupture occurred. However, the higher restenosis rate in women may restrict the use of polyester patch to men.

We followed 278 consecutive patients undergoing carotid artery surgery between January 1985 and December 1989 using a computerized surveillance program file with automatic carotid and coronary artery follow-up investigations every six months. Combined postoperative neurologic mortality and morbidity was 1.7%. During the mean follow-up period of 30 months, 10 patients died, four due to myocardial infarction. Actuarial rates of survival and freedom from cerebral vascular accidents at 36 months were 94% and 95.8%, respectively. No fatalities due to cerebral vascular accidents occurred during follow-up. Eleven patients had myocardial infarction, an actuarial rate of 6% at 36 months: 18 patients experienced angina pectoris, while seven sustaned silent electrical myocardial ischemia. Findings on myocardial angioscintiscans and coronary artery arteriograms led to four aortocoronary bypasses and seven percutaneous coronary artery dilatations. Duplex scanning documented three asymptomatic carotid restenoses of ≥ 80%, which were operated upon, and 32 contralateral carotid artery stenoses ranging between 80% and 99%, 24 of which were asymptomatic. Twenty-eight patients underwent secondary contralateral carotid artery revascularization. No one with contralateral carotid artery stenosis < 80% experienced a carotid artery ischemic event. These results clearly show the value of cardiac and neurologic surveillance of patients operated on for carotid artery stenosis.

Steric effects on electronic transitions for the systems 1and 2are reported. The π → π* transitions studied are defined precisely by means of CNDO/S calculations.