303 research outputs found

    Neither predator nor prey:What trafficking discourses miss about masculinities, mobility and work

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    Within trafficking discourses, men appear as predatory and exploitative, while boys appear as victims. This flattens the complexities of social life and obscures the ways that constructs of masculinity frame the trajectories of labour migrants and their brokers. This article challenges those discourses, drawing on research with two groups of labour migrants characterized as ‘victims of trafficking’, as well as with ‘traffickers’ who help them to move and work. The first are adolescents moving from Benin to the gravel quarries of Abeokuta, Nigeria. The second are adults from across West Africa who have made the illegal journey to Italy, where they live in ‘ghettos’ and work as gang labourers on harvests. In each case, migrants and their brokers come from the same or similar communities; (shared) ideals of masculinity structure their mobility and labour. Gendered transitions towards adulthood, the pressure to attain riches and status and a duty of responsibility to those younger and less successful are important. A focus on their masculinities takes us beyond ‘victim-perpetrator’ dyads.</p

    Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations

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    Fludarabine, cyclophosphamide and rituximab (FCR) is first-line treatment for medically fit chronic lymphocytic leukemia (CLL) patients, however despite good response rates many patients eventually relapse. Whilst recent high-throughput studies have identified novel recurrent genetic lesions in adverse-prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, BIRC3) a large proportion of cases (19.5%) harbored mutations in RPS15, a gene encoding a component of the 40S ribosomal subunit. Extended screening, totaling 1119 patients, supported a role for RPS15 mutations in aggressive CLL, with one-third of RPS15-mutant cases also carrying TP53 aberrations. In most cases selection of dominant, relapse-specific subclones was observed over time. However, RPS15 mutations were clonal prior to treatment and remained stable at relapse. Notably, all RPS15 mutations represented somatic missense variants and resided within a 7 amino-acid evolutionarily conserved region. We confirmed the recently postulated direct interaction between RPS15 and MDM2/MDMX and transient expression of mutant RPS15 revealed defective regulation of endogenous p53 compared to wildtype RPS15. In summary, we provide novel insights into the heterogeneous genetic landscape of CLL relapsing after FCR treatment and highlight a novel mechanism underlying clinical aggressiveness involving a mutated ribosomal protein, potentially representing an early genetic lesion in CLL pathobiology

    Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders

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    Background For patients with psychiatric illnesses remaining refractory to \u27tandard\u27 therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered \u27stablished\u27 in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient\u27s capacity and autonomy, multifaceted preoperative as well as postoperative long-term follow-p evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety

    Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn\u27s Disease But Not Ulcerative Colitis.

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    BACKGROUND & AIMS: Patients with Crohn\u27s disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration. METHODS: We analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (\u3e2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes. RESULTS: Within 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P \u3c .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC. CONCLUSIONS: Patients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

    Dissecting Allele Architecture of Early Onset IBD Using High-Density Genotyping

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    BACKGROUND: The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent. METHODS: We performed a fine mapping association study of early onset IBD using high-density Immunochip genotyping on 1008 pediatric-onset IBD cases (801 Crohn\u27s disease; 121 ulcerative colitis and 86 IBD undetermined) and 1633 healthy controls. Of the 158 SNP genotypes obtained (out of the 163 identified in adult onset), this study replicated 4% (5 SNPs out of 136) of the SNPs identified in the Crohn\u27s disease (CD) cases and 0.8% (1 SNP out of 128) in the ulcerative colitis (UC) cases. Replicated SNPs implicated the well known NOD2 and IL23R. The point estimate for the odds ratio (ORs) for NOD2 was above and outside the confidence intervals reported in adult onset. A polygenic liability score weakly predicted the age of onset for a larger collection of CD cases (p\u3c 0.03, R2= 0.007), but not for the smaller number of UC cases. CONCLUSIONS: The allelic architecture of common susceptibility variants for early onset IBD is similar to that of adult onset. This immunochip genotyping study failed to identify additional common variants that may explain the distinct phenotype that characterize early onset IBD. A comprehensive dissection of genetic loci is necessary to further characterize the genetic architecture of early onset IBD

    Uncertainty and sensitivity analysis of the effect of the mean energy and FWHM of the initial electron fluence on the Bremsstrahlung photon spectra of linear accelerators

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    A calculation of the correct dose in radiation therapy requires an accurate description of the radiation source because uncertainties in characterization of the linac photon spectrum are propagated through the dose calculations. Unfortunately, detailed knowledge of the initial electron beam parameters is not readily available, and many researchers adjust the initial electron fluence values by trial-and-error methods. The main goal of this work was to develop a methodology to characterize the fluence of initial electrons before they hit the tungsten target of an Elekta Precise medical linear accelerator. To this end, we used a Monte Carlo technique to analyze the influence of the characteristics of the initial electron beam on the distribution of absorbed dose from a 6 MV linac photon beam in a water phantom. The technique is based on calculations with Software for Uncertainty and Sensitivity Analysis (SUSA) and Monte Carlo simulations with the MCNP5 transport code. The free parameters used in the SUSA calculations were the mean energy and full-width-at-half-maximum (FWHM) of the initial electron distribution. A total of 93 combinations of these parameters gave initial electron fluence configurations. The electron spectra thus obtained were used in a simulation of the electron transport through the target of the linear accelerator, which produced different photon (Bremsstrahlung) spectra. The simulated photon spectra were compared with the 6-MV photon spectrum provided by the linac manufacturer (Elekta). This comparison revealed how the mean energy and FWHM of the initial electron fluence affect the spectrum of the generated photons. This study has made it possible to fine-tune the examined electron beam parameters to obtain the resulted absorbed doses with acceptable accuracy (error < 1%). (C) 2012 Elsevier Ltd. All rights reserved.Juste Vidal, BJ.; Miró Herrero, R.; Verdú Martín, GJ.; Macian, R. (2012). Uncertainty and sensitivity analysis of the effect of the mean energy and FWHM of the initial electron fluence on the Bremsstrahlung photon spectra of linear accelerators. Applied Radiation and Isotopes. 70(7):1267-1271. doi:10.1016/j.apradiso.2012.03.040S1267127170

    Chiral bosonization for non-commutative fields

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    A model of chiral bosons on a non-commutative field space is constructed and new generalized bosonization (fermionization) rules for these fields are given. The conformal structure of the theory is characterized by a level of the Kac-Moody algebra equal to (1+θ2)(1+ \theta^2) where θ\theta is the non-commutativity parameter and chiral bosons living in a non-commutative fields space are described by a rational conformal field theory with the central charge of the Virasoro algebra equal to 1. The non-commutative chiral bosons are shown to correspond to a free fermion moving with a speed equal to c′=c1+θ2 c^{\prime} = c \sqrt{1+\theta^2} where cc is the speed of light. Lorentz invariance remains intact if cc is rescaled by c→c′c \to c^{\prime}. The dispersion relation for bosons and fermions, in this case, is given by ω=c′∣k∣\omega = c^{\prime} | k|.Comment: 16 pages, JHEP style, version published in JHE
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