Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian childhood obesity treatment trial (MASCOT)

Context. Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. Aim. To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. Methods. Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). Results. The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. Conclusions. Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes

Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin.

The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not

On a incendié la forêt.

L'incendie occupe une place particulière dans la représentation sociale de la forêt méditerranéenne

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

What causes the inverse relationship between primary production and export efficiency in the Southern Ocean?

The ocean contributes to regulating atmospheric CO2 levels, partly via variability in the fraction of primary production (PP) which is exported out of the surface layer (i.e. the e-ratio). Southern Ocean studies have found that, contrary to global scale analyses, an inverse relationship exists between e-ratio and PP. This relationship remains unexplained, with potential hypotheses being i) large export of dissolved organic carbon (DOC) in high PP areas, ii) strong surface microbial recycling in high PP regions and/ or iii) grazing mediated export varies inversely with PP. We find that the export of DOC has a limited influence in setting the negative e-ratio/PP relationship. However, we observed that at sites with low PP and high e-ratios, zooplankton mediated export is large and surface microbial abundance low suggesting that both are important drivers of the magnitude of the e-ratio in the Southern Ocean

Effect of a Successful Intensive Lifestyle Program on Insulin Sensitivity and Glucose Tolerance in Obese Youth

OBJECTIVE—To evaluate the impact on glucose metabolism of a lifestyle program (the Yale Bright Bodies Program) for obese children

Few-shot Classifier GAN

Fine-grained image classification with a few-shot classifier is a highly challenging open problem at the core of a numerous data labeling applications. In this paper, we present Few-shot Classifier Generative Adversarial Network as an approach for few-shot classification. We address the problem of few-shot classification by designing a GAN in which the discriminator and the generator compete to output labeled data in any case. In contrast to previous methods, our techniques generate then classify images into multiple fake or real classes. A key innovation of our adversarial approach is to allow fine-grained classification using multiple fake classes with semi-supervised deep learning. A major strength of our techniques lies in its label-agnostic characteristic, in the sense that the system handles both labeled and unlabeled data during training. We validate quantitatively our few-shot classifier on the MNIST and SVHN datasets by varying the ratio of labeled data over unlabeled data in the training set. Our quantitative analysis demonstrates that our techniques produce better classification performance when using multiple fake classes and larger amount of unlabelled data

First numerical analysis of runaway electron generation in tungsten-rich plasmas towards ITER

The disruption and runaway electron analysis model code was extended to include tungsten impurities in disruption simulations with the aim of studying the runaway electron (RE) generation. This study investigates RE current sensitivity on the following plasma parameters and modelling choices: tungsten concentration, magnetic perturbation strength, electron modelling, thermal quench time and tokamak geometry: ITER-like or ASDEX-like. Our investigation shows that a tungsten concentration below 10-3 does not cause significant RE generation on its own. However, at higher concentrations it is possible to reach a very high RE current. Out of the two tested models of electrons in plasma: fluid and isotropic (kinetic), results from the fluid model are more conservative, which is useful when it comes to safety analysis. However, these results are overly pessimistic when compared to the isotropic model, which is based on a more reliable approach. Our results also show that the hot-tail RE generation mechanism is dominant as a primary source of RE in tungsten induced disruptions, usually providing orders of magnitude higher RE seed than Dreicer generation. We discuss best practices for simulations with tungsten-rich plasma, present the dependence of the safety limits on modelling choices and highlight the biggest shortcoming of the current simulation techniques. The obtained results pave the way for a wider analysis of tungsten impact on the disruption dynamics, including the mitigation techniques for ITER in the case of strong contamination of the plasma with tungsten

Feasibility and safety of a group physical activity program for youth with type 1 diabetes

Background/ObjectiveMany adolescents with type 1 diabetes do not achieve 60 minutes of daily moderate to vigorous physical activity (MVPA). Recognizing the importance of peer influence during adolescence, we evaluated the feasibility and safety of a group MVPA intervention for this population. SubjectsEighteen adolescents with type 1 diabetes (age 14.1±2.3yr, female 67%, Black or Latino 67%, median body mass index 92%’ile, A1c 79.9±25.1 mmol/mol, 9.5±2.3%). MethodsIntervention sessions (35min MVPA and 45min discussion) occurred 1x/week for 12 weeks. Feasibility and safety metrics were enrollment, completion of intervention and assessments, cost, and hypoglycemia rates. Participants completed MVPA (accelerometry), and exploratory nutritional, psychosocial, clinical, and fitness variable assessments at baseline, 3mo, and 7mo. Hedges’ effect sizes were calculated. ResultsEnrollment was 16% and intervention completion 56%. Assessment completion at 7mo was 67% for MVPA, nutrition, and fitness, 83% for psychosocial assessments, and 94% for clinical assessments. Cost was $1,241 per completing participant. One episode of mild hypoglycemia occurred during the sessions (0.6%). Self-reported daily fruit/vegetable servings (d= -0.72) and diabetes self-management behaviors decreased over time (d= -0.40). In the 10 completers, endurance run score improved (d= 0.49) from low baseline levels, while systolic blood pressure decreased (d= -0.75) and low-density lipoprotein increased (d= 0.49) but stayed within normal ranges.ConclusionsThe protocol for the group MVPA intervention was safe and had some feasibility metrics meriting further investigation. MVPA levels and glycemic control remained sub-optimal, suggesting the need for more intensive interventions for this population. <br/