Modeling the dynamics of bivalent histone modifications

Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have "bivalent domains" in which the nucleosomes contain both active (H3K4me3) and repressive (H3K27me3) marks. It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear. Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns. We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states.Comment: 23 pages, 10 figure

Cardiovascular disease and hypertension in sub-Saharan Africa : burden, risk and interventions

Cardiovascular disease, including stroke, heart failure and kidney disease, have been common in sub-Saharan Africa for many years and rapid urbanization is causing an upsurge of ischaemic heart disease and metabolic disorders. At least two thirds of cardiovascular deaths now occur in low-and-middle-income countries, bringing a double burden of disease to poor and developing world economies. High blood pressure (or hypertension) is by far the commonest underlying risk factor for cardiovascular disease. Its prevention, detection, treatment and control in sub-Saharan Africa are haphazard and sub-optimal. This is due to a combination of lack of resources and healthcare systems, non-existent effective preventive strategies at a population level, lack of sustainable drug therapy and barriers to complete adherence to prescribed medications. The economic impact in regard to loss of productive years of life and the need to divert scarce resources to tertiary care is substantial

A Dual-phase Xenon TPC for Scintillation and Ionisation Yield Measurements in Liquid Xenon

A small-scale, two-phase (liquid/gas) xenon time projection chamber (Xurich II) was designed, constructed and is under operation at the University of Zurich. Its main purpose is to investigate the microphysics of particle interactions in liquid xenon at energies below 50 keV, which are relevant for rare event searches using xenon as target material. Here we describe in detail the detector, its associated infrastructure, and the signal identification algorithm developed for processing and analysing the data. We present the first characterisation of the new instrument with calibration data from an internal 83m-Kr source. The zero-field light yield is 15.0 and 14.0 photoelectrons/keV at 9.4 keV and 32.1 keV, respectively, and the corresponding values at an electron drift field of 1 kV/cm are 10.8 and 7.9 photoelectrons/keV. The charge yields at these energies are 28 and 31 electrons/keV, with the proportional scintillation yield of 24 photoelectrons per one electron extracted into the gas phase, and an electron lifetime of 200 $\mu$s. The relative energy resolution, $\sigma/E$, is 11.9 % and 5.8 % at 9.4 keV and 32.1 keV, respectively using a linear combination of the scintillation and ionisation signals. We conclude with measurements of the electron drift velocity at various electric fields, and compare these to literature values.Comment: 11 pages, 14 figure

Sleep duration and incidence of obesity in infants, children and adolescents : a systematic review and meta-analysis of prospective studies

Study Objective: To assess the prospective relationship between sleep and obesity in a paediatric population. Methods: We performed a systematic search using PubMed, Embase, Web of Science and Cochrane (up to 25th September 2017). Included studies were prospective, had follow-up >1 year, had duration of sleep at baseline, and measures of incidence of overweight or obesity and/or changes in body mass index (BMI) z-score and BMI during follow-up. We extracted relative risks or changes in BMI z-score or BMI and 95% confidence intervals (CI) and pooled them using a random effect model. Results: Forty-two studies were included but, as there was significant heterogeneity, results are presented by age strata. Short sleep was associated with a greater risk of developing overweight or obesity in infancy (7 Studies, 14 738 participants, RR: 1.40; 95% CI 1.19 to 1.65; p<0.001), early childhood (8 Studies, 31 104 participants, RR: 1.57; 1.40 to 1.76; p<0.001), middle childhood (3 studies, 3 005 participants, RR: 2.23; 2.18 to 2.27; p<0.001) and adolescence (3 studies, 26 652 participants, RR: 1.30; 1.11 to 1.53; p<0.002). Sleep duration was also associated with a significant change in BMI z-score (14 studies, 18 cohorts, 31 665 participants) (mean difference -0.03; -0.04 to -0.01 per h sleep; P=0.001) and in BMI (16 studies, 24 cohorts, 24 894 participants) (mean difference -0.03 kg/m2; -0.04 to -0.01 for every h of increase in sleep; P=0.001). Conclusions: Short sleep duration is a risk factor or marker of the development of obesity in infants, children and adolescents

The association between OCD and shame : A systematic review and meta-analysis

Background Due to rumination and self-criticism over unwanted obsessions and repetitive rituals, shame is a common emotion experienced by individuals with obsessive–compulsive disorder (OCD). Shame is also theorized to have relevance to unacceptable thoughts in OCD. However, empirical research looking at the relationship between OCD and shame is still emerging and findings have been mixed. Objectives Our review systematically examines the association of shame with OCD and unacceptable thoughts. Methods The last updated search was conducted across five databases between 27 and 29 February 2022. The final selection included 20 papers, 18 of which were used in the primary meta-analysis to calculate pooled effect sizes between OCD and shame measures using a random effects model. In a separate analysis, three papers were used to calculate pooled effect sizes between shame and OCD symptom dimensions also using a random effects model. Results The meta-analyses identified a significant, moderate and positive correlation between total OCD and shame scores r = .352, 95% CI [0.260, 0.438]. In addition, significant, weak and positive relationships were found between shame and three OCD symptom dimensions: unacceptable thoughts r = .252, 95% CI [−0.467, 0.9708], harm obsessions r = .224, CI [−0.190, 0.638] and symmetry concerns r = .200, CI [−0.108, 0.509]. Limitations Shame measures in the reviewed studies were not specific to OCD, and between-study variance in the analyses examining unacceptable thoughts was significant. Conclusions Our findings support a medium positive relationship between shame and OCD. As shame in OCD can be a barrier to seeking treatment and impair quality of life, it is imperative to address this emotion through psychoeducation, assessment and treatment

Systematic review and meta-analysis of randomised controlled trials on the effects of potassium supplements on serum potassium and creatinine

Objectives: High potassium intake could prevent stroke, but supplementation is considered hazardous. We assessed the effect of oral potassium supplementation on serum or plasma potassium levels and renal function. Setting: We updated a systematic review of the effects of potassium supplementation in randomised clinical trials carried out worldwide, published in 2013, extending it to July 2015. We followed the PRISMA guidelines. Participants: Any individual taking part in a potassium supplementation randomised clinical trial. Studies included met the following criteria: randomised clinical trials, potassium supplement given and circulating potassium levels reported. Intervention: Oral potassium supplementation. Primary outcome measures: Serum or plasma potassium and serum or plasma creatinine. Results: A total of 20 trials (21 independent groups) were included (1216 participants from 12 different countries). All but 2 were controlled (placebo n=16, control n=2). Of these trials, 15 were crossover, 4 had a parallel group and 1 was sequential. The duration of supplementation varied from 2 to 24 weeks and the amount of potassium given from 22 to 140 mmol/day. In the pooled analysis, potassium supplementation caused a small but significant increase in circulating potassium levels (weighted mean difference (WMD) 0.14 mmol/L, 95% CI 0.09 to 0.19, p<1×10−5), not associated with dose or duration of treatment. The average increase in urinary potassium excretion was 45.75 mmol/24 hours, 95% CI 38.81 to 53.69, p<1×10−5. Potassium supplementation did not cause any change in circulating creatinine levels (WMD 0.30 µmol/L, 95% CI −1.19 to 1.78, p=0.70). Conclusions: In short-term studies of relatively healthy persons, a moderate oral potassium supplement resulted in a small increase in circulating potassium levels and no change in renal function

Systematic review and meta-analyses of the relationship between short sleep and incidence of obesity and effectiveness of sleep interventions on weight gain in preschool children

The aim of this study is to determine (a) whether short sleep is associated with the incidence of obesity and (b) whether interventions beneficial for sleep reduce weight gain in preschool children. We systematically searched PubMed, Embase, Web of Science and Cochrane up to 12/09/2019. (a) Studies that were included were prospective, had follow‐up ≥1 year, with sleep duration at baseline and required outcome measures. (b) Intervention trials with sleep intervention and measures of overweight or obesity were included. Data were extracted according to PRISMA guidelines. (a) The risk of developing overweight/obesity was greater in short sleeping children (13 studies, 42 878 participants, RR: 1.54; 95% CI, 1.33 to 1.77; p < 0.001). Sleep duration was associated with a significant change in BMI z‐score (10 studies, 11 cohorts and 29 553 participants) (mean difference: −0.02 unit per hour sleep; −0.03 to −0.01; p < 0.001). (b) Four of the five intervention studies reported improved outcomes: for BMI (−0.27 kg/m2; −0.50 to −0.03; p = 0.03); for BMI z‐score (−0.07 unit; −0.12 to −0.02; p = 0.006). Short sleep duration is a risk factor or marker of the development of obesity in preschool children. Intervention studies suggest that improved sleep may be beneficially associated with a reduced weight gain in these children