The Earliest Origins of Genetic Nurture: The Prenatal Environment Mediates the Association Between Maternal Genetics and Child Development

Observed genetic associations with educational attainment may be due to direct or indirect genetic influences. Recent work highlights genetic nurture, the potential effect of parents’ genetics on their child’s educational outcomes via rearing environments. To date, few mediating childhood environments have been tested. We used a large sample of genotyped mother–child dyads (N = 2,077) to investigate whether genetic nurture occurs via the prenatal environment. We found that mothers with more education-related genes are generally healthier and more financially stable during pregnancy. Further, measured prenatal conditions explain up to one third of the associations between maternal genetics and children’s academic and developmental outcomes at the ages of 4 to 7 years. By providing the first evidence of prenatal genetic nurture and showing that genetic nurture is detectable in early childhood, this study broadens our understanding of how parental genetics may influence children and illustrates the challenges of within-person interpretation of existing genetic associations

Accuracy and Responsiveness of the stepwatch activity monitor and ActivPAL in patients with CODP when walking with and without a rollator

Purpose: To evaluate the measurement properties of the StepWatch™ Activity Monitor (SAM) and ActivPAL in COPD. Method: Whilst wearing both monitors, participants performed walking tasks at two self-selected speeds, with and without a rollator. Steps obtained using the monitors were compared with that measured by direct observation. Results: Twenty participants aged 73 ± 9 years (FEV1 = 35 ± 13% pred; 8 males) completed the study. Average speeds for the slow and normal walking tasks were 34 ± 7 m•min−1and 46 ± 10 m•min−1, respectively. Agreement between steps recorded by the SAM with steps counted was similar irrespective of speed or rollator use (p = 0.63) with a mean difference and limit of agreement (LOA) of 2 steps•min−1 and 6 steps•min−1, respectively. Agreement for the ActivPAL was worse at slow speeds (mean difference 7 steps•min−1; LOA 10 steps•min−1) compared with normal speeds (mean difference 4 steps•min−1; LOA 5 steps•min−1) (p = 0.03), but was unaffected by rollator use. The change in step rate between slow and normal walking via direct observation was 12 ± 7 steps•min−1 which was similar to that detected by the SAM (12 ± 6 steps•min−1) and ActivPAL (14 ± 7 steps•min−1). Conclusions: The SAM can be used to detect steps in people who walk very slowly including those who use a rollator. Both devices were sensitive to small changes

Improving on whole-brain radiotherapy in patients with large brain metastases: a planning study to support the AROMA clinical trial

PURPOSE: To develop a novel dose-escalated volumetric modulated arc therapy (VMAT) strategy for patients with single or multiple large brain metastases which can deliver a higher dose to individual lesions for better local control (LC), and to compare dosimetry between whole brain radiotherapy (WBRT), hippocampal-sparing whole brain radiotherapy (HS-WBRT) and different VMAT-based focal radiotherapy approaches. METHODS AND MATERIALS: We identified 20 patients with one to ten brain metastases and at least one lesion larger than 15 cm3 who had received WBRT as part of routine care. For each patient, we designed and evaluated five radiotherapy treatment plans, including WBRT, HS-WBRT and three VMAT dosing models. A dose of 20 Gy in 5 fractions was prescribed to the whole brain or target volumes depending on the plan, with higher doses to smaller lesions and dose-escalated inner planning target volumes (DE-iPTV) in VMAT plans, respectively. Treatment plans were evaluated using the efficiency index, mean dose and D0.1cc to the target volumes and organs at risk. RESULTS: Compared with WBRT, VMAT plans achieved a significantly more efficient dose distribution in brain lesions, especially with our DE-iPTV model, while minimising the dose to the normal brain and other organs at risks (OARs) (p < 0.05). CONCLUSIONS: VMAT plans obtained higher doses to brain metastases and minimised doses to OARs. Dose-escalated VMAT for larger lesions allows higher radiotherapy doses to be delivered to larger lesions while maintaining safe doses to OARs

The validity and reliability of observational assessment tools available to measure fundamental movement skills in school-age children: A systematic review

Background Fundamental Movement Skills (FMS) play a critical role in ontogenesis. Many children have insufficient FMS, highlighting the need for universal screening in schools. There are many observational FMS assessment tools, but their psychometric properties are not readily accessible. A systematic review was therefore undertaken to compile evidence of the validity and reliability of observational FMS assessments, to evaluate their suitability for screening. Methods A pre-search of ‘fundamental movement skills’ OR ‘fundamental motor skills’ in seven online databases (PubMed, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, EBSCO SPORTDiscus, Ovid PsycINFO and Web of Science) identified 24 assessment tools for school-aged children that: (i) assess FMS; (ii) measure actual motor competence and (iii) evaluate performance on a standard battery of tasks. Studies were subsequently identified that: (a) used these tools; (b) quantified validity or reliability and (c) sampled school-aged children. Study quality was assessed using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklists. Results Ninety studies were included following the screening of 1863 articles. Twenty-one assessment tools had limited or no evidence to support their psychometric properties. The Test of Gross Motor Development (TGMD, n = 34) and the Movement Assessment Battery for Children (MABC, n = 37) were the most researched tools. Studies consistently reported good evidence for validity, reliability for the TGMD, whilst only 64% of studies reported similarly promising results for the MABC. Twelve studies found good evidence for the reliability and validity of the Bruininks-Oseretsky Test of Motor Proficiency but poor study quality appeared to inflate results. Considering all assessment tools, those with promising psychometric properties often measured limited aspects of validity/reliability, and/or had limited feasibility for large scale deployment in a school-setting. Conclusion There is insufficient evidence to justify the use of any observational FMS assessment tools for universal screening in schools, in their current form

Ecological effects of a supra-seasonal drought on macroinvertebrate communities differ between near-perennial and ephemeral river reaches

The duration, intensity and frequency of hydrological droughts are predicted to increase significantly over the 21st century globally, threatening the long-term stability of lotic communities. In this paper we examine the recovery and recolonization of macroinvertebrate taxa in ephemeral and near perennial reaches of the River Lathkill (UK) after a supra-seasonal drought event. Following flow resumption, species accumulation (recolonization) occurred rapidly over a 4-month period, with a steady increase observed thereafter. Taxonomic richness was significantly higher in the section with near perennial flow after the first month of the study than the naturally ephemeral reach. Serial correlation was observed in the near perennial section but not in the upstream ephemeral reach. Serial correlation in the near perennial section may reflect: (1) the ongoing process of recovery or (2) the macroinvertebrate community following a new ecological trajectory. Our results suggest that supra-seasonal droughts may cause initial reductions in lotic diversity during stream desiccation events but may re-set ecological succession and/or temporarily provide new ecological niches, thereby supporting increased taxonomic diversity when the full range of hydrological conditions are considered. Quantifying the recovery of ecological communities following supra-seasonal drought can provide information to help develop ecologically effective conservation and management strategies

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

The Prevalence and Risk Factors for Pneumococcal Colonization of the Nasopharynx among Children in Kilifi District, Kenya

BACKGROUND: Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine-serotype pneumococci but increase in the carriage of non-vaccine serotypes. We studied the epidemiology of carriage among children 3-59 months old before vaccine introduction in Kilifi, Kenya. METHODS: In a rolling cross-sectional study from October 2006 to December 2008 we approached 3570 healthy children selected at random from the population register of the Kilifi Health and Demographic Surveillance System and 134 HIV-infected children registered at a specialist clinic. A single nasopharyngeal swab was transported in STGG and cultured on gentamicin blood agar. A single colony of pneumococcus was serotyped by Quellung reaction. RESULTS: Families of 2840 children in the population-based sample and 99 in the HIV-infected sample consented to participate; carriage prevalence was 65.8% (95% CI, 64.0-67.5%) and 76% (95% CI, 66-84%) in the two samples, respectively. Carriage prevalence declined progressively with age from 79% at 6-11 months to 51% at 54-59 months (p<0.0005). Carriage was positively associated with coryza (Odds ratio 2.63, 95%CI 2.12-3.25) and cough (1.55, 95%CI 1.26-1.91) and negatively associated with recent antibiotic use (0.53 95%CI 0.34-0.81). 53 different serotypes were identified and 42% of isolates were of serotypes contained in the 10-valent PCV. Common serotypes declined in prevalence with age while less common serotypes did not. CONCLUSION: Carriage prevalence in children was high, serotypes were diverse, and the majority of strains were of serotypes not represented in the 10-valent PCV. Vaccine introduction in Kenya will provide a natural test of virulence for the many circulating non-vaccine serotypes