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

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.

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

Particle fluxes associated with mesoscale eddies in the Sargasso Sea

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 1426-1444, doi:10.1016/j.dsr2.2008.02.007.We examined the impact of a cyclonic eddy and mode-water eddy on particle flux in the Sargasso Sea. The primary method used to quantify flux was based upon measurements of the natural radionuclide, 234Th, and these flux estimates were compared to results from sediment traps in both eddies, and a 210Po/210Pb flux method in the mode-water eddy. Particulate organic carbon (POC) fluxes at 150m ranged from 1 to 4 mmol C m-2 d-1 and were comparable between methods, especially considering differences in integration times scales of each approach. Our main conclusion is that relative to summer mean conditions at the Bermuda Atlantic Time-series Study (BATS) site, eddy-driven changes in biogeochemistry did not enhance local POC fluxes during this later, more mature stage of the eddy life cycle (>6 months old). The absence of an enhancement in POC flux puts a constraint on the timing of higher POC flux events, which are thought to have caused the local O2 minima below each eddy, and must have taken place >2 months prior to our arrival. The mode-water eddy did enhance preferentially diatom biomass in its center where we estimated a factor of 3 times higher biogenic Si flux than the BATS summer average. An unexpected finding in the highly depth resolved 234Th data sets are narrow layers of particle export and remineralization within the eddy. In particular, a strong excess 234Th signal is seen below the deep chlorophyll maxima which we attribute to remineralization of 234Th bearing particles. At this depth below the euphotic zone, de novo particle production in the euphotic zone has stopped, yet particle remineralization continues via consumption of labile sinking material by bacteria and/or zooplankton. These data suggest that further study of processes in ocean layers is warranted not only within, but below the euphotic zone.The EDDIES project was funded by the National Science Foundation Chemical, Biological, and Physical Oceanography Programs. Additional support for HPLC pigment analysis (Dr. Charles Trees, CHORS) was provided by NASA

Expulsion of runaway electrons using ECRH in the TCV tokamak

Runaway electrons (REs) are a concern for tokamak fusion reactors from discharge startup to termination. A sudden localized loss of a multi-megaampere RE beam can inflict severe damage to the first wall. Should a disruption occur, the existence of a RE seed may play a significant role in the formation of a RE beam and the magnitude of its current. The application of central electron cyclotron resonance heating (ECRH) in the Tokamak \`a Configuration Variable (TCV) reduces an existing RE seed population by up to three orders of magnitude within only a few hundred milliseconds. Applying ECRH before a disruption can also prevent the formation of a post-disruption RE beam in TCV where it would otherwise be expected. The RE expulsion rate and consequent RE current reduction are found to increase with applied ECRH power. Whereas central ECRH is effective in expelling REs, off-axis ECRH has a comparatively limited effect. A simple 0-D model for the evolution of the RE population is presented that explains the effective ECRH-induced RE expulsion results from the combined effects of increased electron temperature and enhanced RE transport

Perineal descent and patients’ symptoms of anorectal dysfunction, pelvic organ prolapse, and urinary incontinence

Contains fulltext : 89793.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The aim of this dynamic magnetic resonance (MR) imaging study was to assess the relation between the position and mobility of the perineum and patients' symptoms of pelvic floor dysfunction. METHODS: Patients' symptoms were measured with the use of validated questionnaires. Univariate logistic regression analyses were used to study the relationship between the questionnaires domain scores and the perineal position on dynamic MR imaging, as well as baseline characteristics (age, body mass index, and parity). RESULTS: Sixty-nine women were included in the analysis. Only the domain score genital prolapse was associated with the perineal position on dynamic MR imaging. This association was strongest at rest. CONCLUSIONS: Pelvic organ prolapse symptoms were associated with the degree of descent of the perineum on dynamic MR imaging. Perineal descent was not related to anorectal and/or urinary incontinence symptoms.1 juni 201

Barriers and enablers for participation in healthy lifestyle programs by adolescents who are overweight: a qualitative study of the opinions of adolescents, their parents and community stakeholders

Background: Overweight or obesity during adolescence affects almost 25% of Australian youth, yet limited research exists regarding recruitment and engagement of adolescents in weight-management or healthy lifestyle interventions, or best-practice for encouraging long-term healthy behaviour change. A sound understanding of community perceptions, including views from adolescents, parents and community stakeholders, regarding barriers and enablers to entering and engaging meaningfully in an intervention is critical to improve the design of such programs. Methods: This paper reports findings from focus groups and semi-structured interviews conducted with adolescents (n=44), parents (n=12) and community stakeholders (n=39) in Western Australia. Three major topics were discussed to inform the design of more feasible and effective interventions: recruitment, retention in the program and maintenance of healthy change. Data were analysed using content and thematic analyses.Results: Data were categorised into barriers and enablers across the three main topics. For recruitment, identified barriers included: the stigma associated with overweight, difficulty defining overweight, a lack of current health services and broader social barriers. The enablers for recruitment included: strategic marketing, a positive approach and subsidising program costs. For retention, identified barriers included: location, timing, high level of commitment needed and social barriers. Enablers for retention included: making it fun and enjoyable for adolescents, involving the family, having an on-line component, recruiting good staff and making it easy for parents to attend. For maintenance, identified barriers included: the high degree of difficulty in sustaining change and limited services to support change. Enablers for maintenance included: on-going follow up, focusing on positive change, utilisation of electronic media and transition back to community services. Conclusions: This study highlights significant barriers for adolescents and parents to overcome to engage meaningfully with weight-management or healthy lifestyle programs. A number of enablers were identified to promote ongoing involvement with an intervention. This insight into specific contextual opinions from the local community can be used to inform the delivery of healthy lifestyle programs for overweight adolescents, with a focus on maximising acceptability and feasibility

A prospective evaluation of plasma polyphenol levels and colon cancer risk

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2-transformed multivariable models, equol (odds ratio [OR] per log2-value, 0.86, 95% confidence interval [95%CI]=0.79-0.93; qvalue=0.01) and homovanillic acid (OR per log2-value, 1.46, 95%CI=1.16-1.84; qvalue=0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR=0.61, 95%CI=0.41-0.91, ptrend=0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR=1.72, 95%CI=1.17-2.53, ptrend<0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk, of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis

Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression