Measuring fitness of Kenyan children with polyparasitic infections using the 20-meter shuttle run test as a morbidity metric.

BACKGROUND: To date, there has been no standardized approach to the assessment of aerobic fitness among children who harbor parasites. In quantifying the disability associated with individual or multiple chronic infections, accurate measures of physical fitness are important metrics. This is because exercise intolerance, as seen with anemia and many other chronic disorders, reflects the body's inability to maintain adequate oxygen supply (VO(2) max) to the motor tissues, which is frequently linked to reduced quality-of-life in terms of physical and job performance. The objective of our study was to examine the associations between polyparasitism, anemia, and reduced fitness in a high risk Kenyan population using novel implementation of the 20-meter shuttle run test (20mSRT), a well-standardized, low-technology physical fitness test. METHODOLOGY/PRINCIPAL FINDINGS: Four villages in coastal Kenya were surveyed during 2009-2010. Children 5-18 years were tested for infection with Schistosoma haematobium (Sh), malaria, filaria, and geohelminth infections by standard methods. After anthropometric and hemoglobin testing, fitness was assessed with the 20 mSRT. The 20 mSRT proved easy to perform, requiring only minimal staff training. Parasitology revealed high prevalence of single and multiple parasitic infections in all villages, with Sh being the most common (25-62%). Anemia prevalence was 45-58%. Using multiply-adjusted linear modeling that accounted for household clustering, decreased aerobic capacity was significantly associated with anemia, stunting, and wasting, with some gender differences. CONCLUSIONS/SIGNIFICANCE: The 20 mSRT, which has excellent correlation with VO(2), is a highly feasible fitness test for low-resource settings. Our results indicate impaired fitness is common in areas endemic for parasites, where, at least in part, low fitness scores are likely to result from anemia and stunting associated with chronic infection. The 20 mSRT should be used as a common metric to quantify physical fitness and compare sub-clinical disability across many different disorders and community settings

Understanding suicide attempts among gay men from their self-perceived causes

Gay men are at higher risk of suicidality. This paper describes the causes of suicide attempts as perceived by the men themselves and analyzes their impact on severity and recidivism. Mental health surveys conducted among gay men in Geneva, Switzerland, from two probability-based time-space samples in 2007 and 2011, were merged to yield a combined sample N = 762. Suicide ideation, plans, and attempts were assessed, and respondents who had ever attempted suicide answered open questions about perceived causes which were coded and categorized for analysis within the framework of cultural epidemiology. In all, 16.7% of the respondents reported a suicide attempt in their lifetime (59.5% of them with multiple attempts). At their latest attempt, over two thirds asserted intent to die, and half required medical assistance. There was a wide variety of perceived causes, with most individuals reporting multiple causes and many of the most common causes cited at both the first and most recent subsequent attempts. Social/inter-personal problems constitute the most prominent category. Problems with love/relationship and accepting one's homosexuality figure consistently among the top three causes. Whereas the former tend to be associated with weaker intent to die, the latter are associated with the strongest intent to die and reported at multiple attempts. Problems with family are among the most common perceived causes at first attempt but not at the most recent subsequent attempt. Nevertheless, they tend to be related to the strongest intent to die and the greatest medical severity of all the perceived causes. Ten percent of men attempting suicide cited depression as a cause. Although it tended to be associated with weaker intent to die, depression was most likely to be reported at multiple attempts. Respondent-driven assessment yielded both common and idiosyncratic causes of suicide and their distinct effects. Some of these perceived causes are not prominent in the curren literature, yet they have important implications for understanding risk and preventing suicide among gay men

A novel case of MSTO1 gene related congenital muscular dystrophy with progressive neurological involvement

Recessive mutations in the MSTO1 gene, encoding for a mitochondrial distribution and morphology regulator, have been recently described in a very limited number of patients with multisystem involvement, mostly characterized by myopathy or dystrophy, cerebellar ataxia, pigmentary retinopathy and raised creatine kinase levels. Here we report an additional patient with recessive MSTO1-related muscular dystrophy (MSTO1-RD), and clinical and radiological evidence of progressive cerebellar involvement. Whole-exome sequencing identified two novel MSTO1 missense variants, c.766C > T (p. (Arg256Trp) and c.1435C > T (p. (Pro479Ser), predicted as damaging by in silico tools. We also report a distinct pattern of selective involvement on muscle MRI in MSTO1-RD. This case confirms a consistent MSTO1-related neuromuscular phenotype and in addition suggests a progressive neurological component at least in some patients, in keeping with the mitochondrial role of the defective protein

Non-invasive MR imaging of inflammation in a patient with both asymptomatic carotid atheroma and an abdominal aortic aneurysm: a case report.

Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. USPIO-enhanced MRI imaging is a promising non-invasive method to identify high-risk atheromatous plaque inflammation in vivo in humans, in which areas of focal signal loss on MR images have been shown to correspond to the location of activated macrophages, typically at the shoulder regions of the plaque. This is the first report in humans describing simultaneous USPIO uptake within atheroma in two different arterial territories and again emphasises that atherosclerosis is a truly systemic disease. With further work, USPIO-enhanced MR imaging may be useful in identifying inflamed vulnerable atheromatous plaques in vivo, so refining patient selection for intervention and allowing appropriate early aggressive pharmacotherapy to prevent plaque rupture.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Latent Transformer Models for out-of-distribution detection

Any clinically-deployed image-processing pipeline must be robust to the full range of inputs it may be presented with. One popular approach to this challenge is to develop predictive models that can provide a measure of their uncertainty. Another approach is to use generative modelling to quantify the likelihood of inputs. Inputs with a low enough likelihood are deemed to be out-of-distribution and are not presented to the downstream predictive model. In this work, we evaluate several approaches to segmentation with uncertainty for the task of segmenting bleeds in 3D CT of the head. We show that these models can fail catastrophically when operating in the far out-of-distribution domain, often providing predictions that are both highly confident and wrong. We propose to instead perform out-of-distribution detection using the Latent Transformer Model: a VQ-GAN is used to provide a highly compressed latent representation of the input volume, and a transformer is then used to estimate the likelihood of this compressed representation of the input. We demonstrate this approach can identify images that are both far- and near- out-of-distribution, as well as provide spatial maps that highlight the regions considered to be out-of-distribution. Furthermore, we find a strong relationship between an image's likelihood and the quality of a model's segmentation on it, demonstrating that this approach is viable for filtering out unsuitable images

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

Neutral Higgs bosons in the MNMSSM with explicit CP violation

Within the framework of the minimal non-minimal supersymmetric standard model (MNMSSM) with tadpole terms, CP violation effects in the Higgs sector are investigated at the one-loop level, where the radiative corrections from the loops of the quark and squarks of the third generation are taken into account. Assuming that the squark masses are not degenerate, the radiative corrections due to the stop and sbottom quarks give rise to CP phases, which trigger the CP violation explicitly in the Higgs sector of the MNMSSM. The masses, the branching ratios for dominant decay channels, and the total decay widths of the five neutral Higgs bosons in the MNMSSM are calculated in the presence of the explicit CP violation. The dependence of these quantities on the CP phases is quite recognizable, for given parameter values.Comment: 25 pages, 8 figure

Diagnostic value of non-invasive imaging techniques in the detection of carotid artery stenosis: a systematic review

The purpose of the study was to evaluate the diagnostic performance of non- invasive imaging methods of detecting carotid artery stenosis in comparison to digital subtraction angiography (DSA) by undertaking a systematic review of the literature. The non-invasive methods reviewed include multislice computed tomography (MSCT) angiography, duplex ultrasound (US) and magnetic resonance (MR) angiography.A search of medical databases (PubMed, Medline, ScienceDirect, Proquest) of the English literature was performed and 22 studies with 68 comparisons were found to meet the selection criteria and included in our study. 5 studies were performed with MSCT angiography, 11 with duplex US and 13 with MR angiography. Both duplex US and MR angiography were studied in 7 out of 24 US and MR studies. The diagnostic value of each imaging modality was reviewed in terms of the sensitivity and specificity compared to DSA, which is regarded as the standard method.The mean sensitivity and specificity for MSCT angiography, duplex US and MR angiography were 88% (95% CI: 83%, 92%) and 90% (95% CI: 85%, 94%), 88% (95% CI: 81%, 94%) and 89% (95% CI: 85%, 94%), 94% (95% CI: 90%, 97%) and 89% (95% CI: 85%, 92%), respectively based on overall assessment. The evaluation showed that contrast-enhanced MR angiography has high diagnostic value for detection of more than 50% stenosis of carotid artery stenosis with mean sensitivity and specificity being 95% (95% CI: 92%, 98%) and 91% (95% CI: 86% 95%). When assessment was based on a combination of MR angiography and duplex US, the sensitivity reached the highest value of 98% (95% CI: 96%, 100%). This analysis indicates that MR angiography, especially contrast-enhanced MR angiography could be used as a reliable alternative modality to DSA in the detection of carotid artery stenosis

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

ELSID-Diabetes study-evaluation of a large scale implementation of disease management programmes for patients with type 2 diabetes. Rationale, design and conduct – a study protocol [ISRCTN08471887]

BACKGROUND: Diabetes model projects in different regions of Germany including interventions such as quality circles, patient education and documentation of medical findings have shown improvements of HbA1c levels, blood pressure and occurrence of hypoglycaemia in before-after studies (without control group). In 2002 the German Ministry of Health defined legal regulations for the introduction of nationwide disease management programs (DMP) to improve the quality of care in chronically ill patients. In April 2003 the first DMP for patients with type 2 diabetes was accredited. The evaluation of the DMP is essential and has been made obligatory in Germany by the Fifth Book of Social Code. The aim of the study is to assess the effectiveness of DMP by example of type 2 diabetes in the primary care setting of two German federal states (Rheinland-Pfalz and Sachsen-Anhalt). METHODS/DESIGN: The study is three-armed: a prospective cluster-randomized comparison of two interventions (DMP 1 and DMP 2) against routine care without DMP as control group. In the DMP group 1 the patients are treated according to the current situation within the German-Diabetes-DMP. The DMP group 2 represents diabetic care within ideally implemented DMP providing additional interventions (e.g. quality circles, outreach visits). According to a sample size calculation a sample size of 200 GPs (each GP including 20 patients) will be required for the comparison of DMP 1 and DMP 2 considering possible drop-outs. For the comparison with routine care 4000 patients identified by diabetic tracer medication and age (> 50 years) will be analyzed. DISCUSSION: This study will evaluate the effectiveness of the German Diabetes-DMP compared to a Diabetes-DMP providing additional interventions and routine care in the primary care setting of two different German federal states