Developments in Rare Kaon Decay Physics

We review the current status of the field of rare kaon decays. The study of rare kaon decays has played a key role in the development of the standard model, and the field continues to have significant impact. The two areas of greatest import are the search for physics beyond the standard model and the determination of fundamental standard-model parameters. Due to the exquisite sensitivity of rare kaon decay experiments, searches for new physics can probe very high mass scales. Studies of the k->pnn modes in particular, where the first event has recently been seen, will permit tests of the standard-model picture of quark mixing and CP violation.Comment: One major revision to the text is the branching ratio of KL->ppg, based on a new result from KTeV. Several references were updated, with minor modifications to the text. A total of 48 pages, with 28 figures, in LaTeX; to be published in the Annual Review of Nuclear and Particle Science, Vol. 50, December 200

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Defining PD subtypes — a step toward personalized management?

A recent article published in Brain proposes a clinical method for subtyping Parkinson disease cases on an individual basis, with implications for better patient stratification for personalized medicine. The authors report biological validity in terms of imaging and cerebrospinal fluid parameters, but long-term predictive validity remains to be established.The work of the authors is supported by the NIHR Cambridge Biomedical Research Centre and the Wellcome Trust–Medical Research Council Cambridge Stem Cell Institute

Computation of Solar Radiative Fluxes by 1D and 3D Methods Using Cloudy Atmospheres Inferred from A-train Satellite Data

The main point of this study was to use realistic representations of cloudy atmospheres to assess errors in solar flux estimates associated with 1D radiative transfer models. A scene construction algorithm, developed for the EarthCARE satellite mission, was applied to CloudSat, CALIPSO, and MODIS satellite data thus producing 3D cloudy atmospheres measuring 60 km wide by 13,000 km long at 1 km grid-spacing. Broadband solar fluxes and radiances for each (1 km)2 column where then produced by a Monte Carlo photon transfer model run in both full 3D and independent column approximation mode (i.e., a 1D model)

Do Mismatches between Pre- and Post-Natal Environments Influence Adult Physiological Functioning?

Purpose: Mismatches between pre- and post-natal environments have implications for disease in adulthood. However, less is known about how this mismatch can affect physiological systems more generally, especially at younger ages. We hypothesised that mismatches between pre- and post-natal environments, as measured by the measures of birthweight and adult leg length, would be associated with poorer biomarker levels across five key physiological systems in young adults. Methods: Data were collected from 923, 36 year-old respondents from the West of Scotland Twenty-07 Study. The biomarkers were: systolic blood pressure (sBP); forced expiratory volume (FEV1); glycated haemoglobin (HbA1c); glomerular filtration rate (eGFR); and gamma- glutamyltransferase (GGT). These biomarkers were regressed against pre-natal conditions (birthweight), post-natal conditions (leg length) and the interaction between pre- and post-natal measures. Sex, childhood socioeconomic position and adult lifestyle characteristics were adjusted for as potential effect modifiers and confounders, respectively. Results: There were no associations between birthweight and leg length and sBP, FEV1, HbA1c, or GGT. Higher birthweight and longer leg length were associated with better kidney function (eGFR). However, there was no evidence for mismatches between birthweight and leg length to be associated with worse sBP, FEV1, HbA1c, eGFR or GGT levels (P>0.05). Conclusions: Our hypothesis that early signs of physiological damage would be present in young adults given mismatches in childhood environments, as measured by growth markers, was not proven. This lack of association could be because age 36 is too young to identify significant trends for future health, or the associations simply not being present. © 2014 Robertson, Benzeval

Southampton PRegnancy Intervention for the Next Generation (SPRING):protocol for a randomised controlled trial

BACKGROUND: The nutritional status and health of mothers influence the growth and development of infants during pregnancy and postnatal life. Interventions that focus on improving the nutritional status and lifestyle of mothers have the potential to optimise the development of the fetus as well as improve the health of mothers themselves. Improving the diets of women of childbearing age is likely to require complex interventions that are delivered in a socially and culturally appropriate context. In this study we aim to test the efficacy of two interventions: behaviour change (Healthy Conversation Skills) and vitamin D supplementation, and to explore the efficacy of an intervention that combines both, in improving the diet quality and nutritional status of pregnant women. METHODS/DESIGN: Women attending the maternity hospital in Southampton are recruited at between 8 and 12 weeks gestation. They are randomised to one of four groups following a factorial design: Healthy Conversation Skills support plus vitamin D supplementation (1000 IU cholecalciferol) (n = 150); Healthy Conversation Skills support plus placebo (n = 150); usual care plus vitamin D supplementation (n = 150); usual care plus placebo (n = 150). Questionnaire data include parity, sunlight exposure, diet assessment allowing assessment of diet quality, cigarette and alcohol consumption, well-being, self-efficacy and food involvement. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH) vitamin D. Maternal diet quality and 25(OH) vitamin D are the primary outcomes. Secondary outcomes are women's level of self-efficacy at 34 weeks, pregnancy weight gain, women's self-efficacy and breastfeeding status at one month after birth and neonatal bone mineral content, assessed by DXA within the first 14 days after birth. DISCUSSION: This trial is evaluating two approaches to improving maternal diet: a behaviour change intervention and vitamin D supplementation. The factorial design of this trial has the advantage of enabling each intervention to be tested separately as well as allowing exploration of the synergistic effect of both interventions on women's diets and vitamin D levels. TRIAL REGISTRATION: ISRCTN07227232 . Registered on 13 September 2013

Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

Background: The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD. Methods: Thirty-one CD patients and 7 controls were enrolled. Circulating CD133+ and CD34+ HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3+ lymphoid cells) and the putative ISC compartment (CD133+ and Lgr5+ epithelial cells). Results: At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal. Conclusions: In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission

Interaction of atopy and smoking on respiratory effects of occupational dust exposure: a general population-based study

BACKGROUND: For individual exposures, effect modification by atopy or smoking has been reported on the occurrence of occupational airway disease. It is unclear if effect modification can be studied in a general population by an aggregated exposure measure. Assess relationship between airway obstruction and occupational exposure using a job-exposure-matrix (JEM) classifying jobs into 3 broad types of exposure, and test for effect modification by atopy, and smoking. METHODS: Data from 1,906 subjects were analyzed, all participants of the European Community Respiratory Health Survey. Job titles were categorized by an a priori constructed job exposure matrix into three classes of exposure to respectively organic dust, mineral dust, and gases/ fumes. Relationships were assessed for 'current wheeze', bronchial hyperresponsiveness (BHR), 'current asthma' (wheeze+BHR), and 'chronic bronchitis' (morning phlegm or morning cough), and lung function. RESULTS: Subjects with organic dust exposure in their work environment more frequently had 'current asthma' (OR 1.48, 95% C.I. 0.95;2.30), and a lower FEV(1 )(-59 mL, 95% C.I. -114;-4). The relationship was only present in asthmatic workers, and their risk was four-fold greater than in subjects with either atopy or exposure alone. Mineral dust exposure was associated with 'chronic bronchitis' (OR 2.22, 95% C.I. 1.16;4.23) and a lower FEV(1)/FVC ratio (-1.1%, 95% C.I. -1.8;-0.3). We observed an excess risk in smokers, greater than the separate effects of smoking or mineral dust exposure together. CONCLUSION: Occupational exposure to organic dust is associated with an increased risk of asthma, particularly in atopics. Chronic bronchitis occurs more frequently among individuals exposed to mineral dust, and smoking doubles this risk

Treatment delay among tuberculosis patients in Tanzania: Data from the FIDELIS Initiative

<p>Abstract</p> <p>Background</p> <p>Several FIDELIS projects (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) in Tanzania were conducted by the National Tuberculosis and Leprosy Programme (NTLP) during the years 2004-2008 to strengthen diagnostic and treatment services. These projects collected information on <it>treatment delay </it>and some of it was available for research purposes. With this database our objective was to assess the duration and determinants of treatment delay among new smear positive pulmonary tuberculosis (TB) patients in FIDELIS projects, and to compare delay according to provider visited prior to diagnosis.</p> <p>Methods</p> <p>Treatment delay among new smear positive TB patients was recorded for each patient at treatment initiation and this information was available and fairly complete in 6 out of 57 districts with FIDELIS projects enrolling patients between 2004 and 2007; other districts had discarded their forms at the time of analysis. It was analysed as a cross sectional study.</p> <p>Results</p> <p>We included 1161 cases, 10% of all patients recruited in the FIDELIS projects in Tanzania. Median delay was 12 weeks. The median duration of cough, weight loss and haemoptysis was 12, 8 and 3 weeks, respectively. Compared to Hai district Handeni had patients with longer delays and Mbozi had patients with shorter delays. Urban and rural patients reported similar delays. Patients aged 15-24 years and patients of 65 years or older had longer delays. Patients reporting contact with traditional healers before diagnosis had a median delay of 15 weeks compared to 12 weeks among those who did not. Patients with dyspnoea and with diarrhoea had longer delays.</p> <p>Conclusion</p> <p>In this patient sample in Tanzania half of the new smear positive pulmonary tuberculosis patients had a treatment delay longer than 12 weeks. Delay was similar in men and women and among urban and rural patients, but longer in the young and older age groups. Patients using traditional healers had a 25% longer median delay.</p

Preeclampsia and Blood Pressure Trajectory during Pregnancy in Relation to Vitamin D Status

Every tenth pregnancy is affected by hypertension, one of the most common complications and leading causes of maternal death worldwide. Hypertensive disorders in pregnancy include pregnancy-induced hypertension and preeclampsia. The pathophysiology of the development of hypertension in pregnancy is unknown, but studies suggest an association with vitamin D status, measured as 25-hydroxyvitamin D (25(OH)D). The aim of this study was to investigate the association between gestational 25(OH)D concentration and preeclampsia, pregnancy-induced hypertension and blood pressure trajectory. This cohort study included 2000 women. Blood was collected at the first (T1) and third (T3) trimester (mean gestational weeks 10.8 and 33.4). Blood pressure at gestational weeks 10, 25, 32 and 37 as well as symptoms of preeclampsia and pregnancy-induced hypertension were retrieved from medical records. Serum 25(OH)D concentrations (LC-MS/MS) in T1 was not significantly associated with preeclampsia. However, both 25(OH)D in T3 and change in 25(OH)D from T1 to T3 were significantly and negatively associated with preeclampsia. Women with a change in 25(OH)D concentration of ≥30 nmol/L had an odds ratio of 0.22 (p = 0.002) for preeclampsia. T1 25(OH)D was positively related to T1 systolic (β = 0.03, p = 0.022) and T1 diastolic blood pressure (β = 0.02, p = 0.016), and to systolic (β = 0.02, p = 0.02) blood pressure trajectory during pregnancy, in adjusted analyses. There was no association between 25(OH)D and pregnancy-induced hypertension in adjusted analysis. In conclusion, an increase in 25(OH)D concentration during pregnancy of at least 30 nmol/L, regardless of vitamin D status in T1, was associated with a lower odds ratio for preeclampsia. Vitamin D status was significantly and positively associated with T1 blood pressure and gestational systolic blood pressure trajectory but not with pregnancy-induced hypertension