Young people today: news media, policy and youth justice

The new sociology of childhood sees children as competent social agents with important contributions to make. And yet the phase of childhood is fraught with tensions and contradictions. Public policies are required, not only to protect children, but also to control them and regulate their behaviour. For children and young people in the UK, youth justice has become increasingly punitive. At the same time, social policies have focused more on children's inclusion and participation. In this interplay of conflict and contradictions, the role the media play is critical in contributing to the moral panic about childhood and youth. In this article, we consider media representations of “antisocial” children and young people and how this belies a moral response to the nature of contemporary childhood. We conclude by considering how a rights-based approach might help redress the moralised politics of childhood representations in the media

Paedophiles in the community: inter-agency conflict, news leaks and the local press

This article explores the leaking of confidential information about secret Home Office plans to house convicted paedophiles within a local community (albeit inside a prison). It argues that a politics of paedophilia has emerged in which inter-agency consensus on the issue of ‘what to do’ with high-profile sex offenders has broken down. Accordingly, the article situates newspaper ‘outing’ of paedophiles in the community in relation to vigilante journalism and leaked information from official agencies. The article then presents research findings from a case study of news events set in train following a whistle-blowing reaction by Prison Officers’ Association officials to Home Office plans. Drawing from a corpus of 10 interviews with journalists and key protagonists in the story, the article discusses both the dynamics of whistle blowing about paedophiles and also what happens after the whistle has blown

The Diagnostic Approach to Monogenic Very Early Onset Inflammatory Bowel Disease

Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel disease (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histological features of Crohn’s disease, ulcerative colitis, or IBD unclassified. Defects in interleukin-10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histological and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extraintestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. In addition, we provide approaches for identifying patients likely to have these disorders. We also discuss classic approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects

Development of Red Flags Index for Early Referral of Adults with Symptoms and Signs Suggestive of Crohn's Disease: An IOIBD Initiative

International audience; BACKGROUND AND AIMS:Diagnostic delay is frequent in patients with Crohn's disease (CD). We developed a tool to predict early diagnosis.METHODS:A systematic literature review and 12 CD specialists identified 'Red Flags', i.e. symptoms or signs suggestive of CD. A 21-item questionnaire was administered to 36 healthy subjects, 80 patients with irritable bowel syndrome (non-CD group) and 85 patients with recently diagnosed (<18 months) CD. Patients with CD were asked to recall symptoms and signs they experienced during the 12 months before diagnosis. Multiple logistic regression analyses selected and weighted independent items to construct the Red Flags index. A receiver operating characteristic curve was used to assess the threshold that discriminated CD from non-CD. Association with the Red Flags index relative to this threshold was expressed as the odds ratios (OR).RESULTS:Two hundred and one subjects, CD and non-CD, answered the questionnaire. The multivariate analysis identified eight items independently associated with a diagnosis of CD. A minimum Red Flags index value of 8 was highly predictive of CD diagnosis with sensitivity and specificity bootstrap estimates of 0.94 (95% confidence interval 0.88-0.99) and 0.94 (0.90-0.97), respectively. Positive and negative likelihood ratios were 15.1 (9.3-33.6) and 0.066 (0.013-0.125), respectively. The association between CD diagnosis and a Red Flags index value of ≥8 corresponds to an OR of 290 (p < 0.0001).CONCLUSIONS:The Red Flags index using early symptoms and signs has high predictive value for the diagnosis of CD. These results need prospective validation prior to introduction into clinical practice

Outcome measurement in clinical trials for Ulcerative Colitis: towards standardisation

Clinical trials on novel drug therapies require clear criteria for patient selection and agreed definitions of disease remission. This principle has been successfully applied in the field of rheumatology where agreed disease scoring systems have allowed multi-centre collaborations and facilitated audit across treatment centres. Unfortunately in ulcerative colitis this consensus is lacking. Thirteen scoring systems have been developed but none have been properly validated. Most trials choose different endpoints and activity indices, making comparison of results from different trials extremely difficult. International consensus on endoscopic, clinical and histological scoring systems is essential as these are the key components used to determine entry criteria and outcome measurements in clinical trials on ulcerative colitis. With multiple new therapies under development, there is a pressing need for consensus to be reached

Numerical Investigation of the Performance of Three Hinge Designs of Bileaflet Mechanical Heart Valves

Thromboembolic complications (TECs) of bileaflet mechanical heart valves (BMHVs) are believed to be due to the nonphysiologic mechanical stresses imposed on blood elements by the hinge flows. Relating hinge flow features to design features is, therefore, essential to ultimately design BMHVs with lower TEC rates. This study aims at simulating the pulsatile three-dimensional hinge flows of three BMHVs and estimating the TEC potential associated with each hinge design. Hinge geometries are constructed from micro-computed tomography scans of BMHVs. Simulations are conducted using a Cartesian sharp-interface immersed-boundary methodology combined with a second-order accurate fractional-step method. Leaflet motion and flow boundary conditions are extracted from fluid–structure-interaction simulations of BMHV bulk flow. The numerical results are analyzed using a particle-tracking approach coupled with existing blood damage models. The gap width and, more importantly, the shape of the recess and leaflet are found to impact the flow distribution and TEC potential. Smooth, streamlined surfaces appear to be more favorable than sharp corners or sudden shape transitions. The developed framework will enable pragmatic and cost-efficient preclinical evaluation of BMHV prototypes prior to valve manufacturing. Application to a wide range of hinges with varying design parameters will eventually help in determining the optimal hinge design

Placebo response rate in clinical trials of fistulizing crohn's disease: systematic review and meta-analysis

Background & Aims: It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn’s disease (CD), to understand disease progression, and to calculate sample size. We conducted a systematic review and meta-analysis of rates of response to placebo in trials of patients with fistulizing CD. Methods: We searched MEDLINE, EMBASE, EMBASE CLASSIC, and the Cochrane central register of controlled trials for randomized controlled trials (RCTs) comparing pharmacologic agents with placebo in adults with fistulizing CD. We identified studies that reported complete fistula closure, partial closure, or response. Data were extracted as intention-to-treat analyses and pooled by using a random-effects model. Proportions of patients who received placebo and had complete or partial fistula(e) closure were calculated, with 95% confidence intervals (CIs). The effects of trial characteristics on the magnitude of response to placebo were examined. Results: Thirteen RCTs were eligible for our analysis; these included 579 patients assigned to placebo groups. The pooled rate of response to placebo, among all RCTs, for complete fistula closure was 15.6% (95% CI, 10.9%–20.9%), with significant heterogeneity (I2 = 62.5%, P = .001). The pooled rate of response to placebo for partial fistula closure or response in 9 trials, comprising 423 patients, was 18.3% (95% CI, 14.8%–22.1%). Rates of response to placebo were significantly lower in trials with shorter durations of therapy and shorter intervals to assessment of fistula closure. Neither exposure to the pharmacologic agent during the induction phase of the same (or related) RCT nor concomitant medications had any effect. Conclusions: In a meta-analysis of rate of response to placebo in patients with fistulizing CD, we found that fistulae closed in almost 1/6 patients given placebo in RCTs of pharmacologic agents. Future research should identify characteristics of patients that predict response to placebo

Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis

Abstract Background Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear. Methods Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-gastroparetic controls underwent full-thickness gastric body biopsies. Deep RNA sequencing was performed and pathway analysis of differentially expressed transcripts was done using Ingenuity®. A subset of differentially expressed genes in diabetic gastroparesis was validated in a separate cohort using QT-PCR. Results 111 genes were differentially expressed in diabetic gastroparesis and 181 in idiopathic gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log2fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05). Conclusions Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human gastroparesis.https://deepblue.lib.umich.edu/bitstream/2027.42/145193/1/12920_2018_Article_379.pd

Interactions between Global Health Initiatives and Country Health Systems: The Case of a Neglected Tropical Diseases Control Program in Mali

Prevention of neglected tropical diseases was recently significantly scaled up in sub-Saharan Africa, protecting entire populations with mass distribution of drugs: five different diseases are now addressed simultaneously with a package of four drugs. Some argue however that, similarly to other major control programs dealing with specific diseases, this NTD campaign fails to strengthen health systems and might even negatively affect regular care provision. In 2007, we conducted an exploratory field study in Mali, observing how the program was implemented in two rural areas and how it affected the health system. At the local level, we found that the campaign effects of care delivery differed across health services. In robust and well staffed health centres, the personnel successfully facilitated mass drug distribution while running routine consultations, and overall service functioning benefitted from programme resources. In more fragile health centres however, additional program workload severely disturbed access to regular care, and we observed operational problems affecting the quality of mass drug distribution. Strong health services appeared to be profitable to the NTD control program as well as to general care