Reprogramming within Hours Following Nuclear Transfer into Mouse but not Human Zygotes

Fertilized mouse zygotes can reprogram somatic cells to a pluripotent state. Human zygotes might therefore be useful for producing patient-derived pluripotent stem cells. However, logistical, legal and social considerations have limited the availability of human eggs for research. Here we show that a significant number of normal fertilized eggs (zygotes) can be obtained for reprogramming studies. Using these zygotes, we found that when the zygotic genome was replaced with that of a somatic cell, development progressed normally throughout the cleavage stages, but then arrested before the morula stage. This arrest was associated with a failure to activate transcription in the transferred somatic genome. In contrast to human zygotes, mouse zygotes reprogrammed the somatic cell genome to a pluripotent state within hours after transfer. Our results suggest that there may be a previously unappreciated barrier to successful human nuclear transfer, and that future studies could focus on the requirements for genome activation.Stem Cell and Regenerative Biolog

Rotation and accretion of very low mass objects in the SigmaOri cluster

We report on two photometric monitoring campaigns of Very Low Mass (VLM) objects in the young open cluster around SigmaOrionis. Our targets were pre-selected with multi-filter photometry in a field of 0.36 sqdeg. For 23 of these objects, spanning a mass range from 0.03 to 0.7 MS, we detect periodic variability. Of these, 16 exhibit low-level variability, with amplitudes of less than 0.2 mag in the I-band, which is mostly well-approximated by a sine wave. These periodicities are probably caused by photospheric spots co-rotating with the objects. In contrast, the remaining variable targets show high-level variability with amplitudes ranging from 0.25 to 1.1 mag, consisting of a periodic light variation onto which short-term fluctuations are superimposed. This variability pattern is very similar to the photometric behaviour of solar-mass, classical T Tauri stars. Low-resolution spectra of a few of these objects reveal strong Halpha and Ca-triplet emission, indicative of ongoing accretion processes. This suggests that 5-7% of our targets still possess a circumstellar disk. In combination with previous results for younger objects, this translates into a disk lifetime of 3-4 Myr, significantly shorter than for solar mass stars. The highly variable objects rotate on average slower than the low-amplitude variables, which is expected in terms of a disk-locking scenario. There is a trend towards faster rotation with decreasing mass, which might be caused by shortening of the disk lifetimes or attenuation of magnetic fields.Comment: 19 pages, 14 figures, A&A, in pres

Neighbourhoods for Active Kids: study protocol for a cross-sectional examination of neighbourhood features and children's physical activity, active travel, independent mobility and body size.

INTRODUCTION: New Zealand children's physical activity, including independent mobility and active travel, has declined markedly over recent decades. The Neighbourhoods for Active Kids (NfAK) study examines how neighbourhood built environments are associated with the independent mobility, active travel, physical activity and neighbourhood experiences of children aged 9-12 years in primary and intermediate schools across Auckland, New Zealand's largest city. METHODS AND ANALYSIS: Child-specific indices of walkability, destination accessibility and traffic exposure will be constructed to measure the built environment in 8 neighbourhoods in Auckland. Interactive online-mapping software will be used to measure children's independent mobility and transport mode to destinations and to derive measures of neighbourhood use and perceptions. Physical activity will be measured using 7-day accelerometry. Height, weight and waist circumference will be objectively measured. Parent telephone interviews will collect sociodemographic information and parent neighbourhood perceptions. Interviews with school representative will capture supports and barriers for healthy activity and nutrition behaviours at the school level. Multilevel modelling approaches will be used to understand how differing built environment variables are associated with activity, neighbourhood experiences and health outcomes. DISCUSSION: We anticipate that children who reside in neighbourhoods considered highly walkable will be more physically active, accumulate more independent mobility and active travel, and be more likely to have a healthy body size. This research is timely as cities throughout New Zealand develop and implement plans to improve the liveability of intensifying urban neighbourhoods. Results will be disseminated to participants, local government agencies and through conventional academic avenues

Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond

Environmental and socio-demographic associates of children's active transport to school: a cross-sectional investigation from the URBAN Study

BACKGROUND: Active transport (e.g., walking, cycling) to school (ATS) can contribute to children's physical activity and health. The built environment is acknowledged as an important factor in understanding children's ATS, alongside parental factors and seasonality. Inconsistencies in methodological approaches exist, and a clear understanding of factors related to ATS remains equivocal. The purpose of this study was to gain a better understanding of associates of children's ATS, by considering the effects of daily weather patterns and neighbourhood walk ability and neighbourhood preferences (i.e., for living in a high or low walkable neighbourhood) on this behaviour. METHODS: Data were drawn from the Understanding Relationships between Activity and Neighbourhoods study, a cross-sectional study of physical activity and the built environment in adults and children in four New Zealand cities. Parents of participating children completed an interview and daily trip diary that assessed their child's mode of travel to school, household and individual demographic information, and parental neighbourhood preference. Daily weather data were downloaded from New Zealand's national climate database. Geographic information systems-derived variables were calculated for distance to school and neighbourhood walkability. Bivariate analyses were conducted with ATS and potential associates; factors related to ATS at p less than 0.20 were considered simultaneously in generalized estimation equation models, and backwards elimination of non-significant factors was conducted; city was treated as a fixed effect in all models. RESULTS: A total of 217 children aged 6.5-15 years participated in this study. Female sex, age, city, household income, limited/no car access, residing in zone of school, shorter distance to school, neighbourhood self selection, rainfall, and sunlight hours were simultaneously considered in multivariate generalised estimation equation modelling (all p less than 0.20 in bivariate analyses). After elimination of non-significant factors, age (p = 0.005), shorter distance to school (p less than 0.001), city (p = 0.03), and neighbourhood self selection (p = 0.04) remained significantly associated with ATS in the multivariate analysis. CONCLUSION: Distance to school is the prevailing environmental influencing factor on children's ATS. This study, in conjunction with previous research, suggests that school siting is likely an important associate of children's ATS

Understanding the Relationship between Activity and Neighbourhoods (URBAN) Study: research design and methodology

<p>Abstract</p> <p>Background</p> <p>Built environment attributes are recognized as being important contributors to physical activity (PA) engagement and body size in adults and children. However, much of the existing research in this emergent public health field is hindered by methodological limitations, including: population and site homogeneity, reliance on self-report measures, aggregated measures of PA, and inadequate statistical modeling. As an integral component of multi-country collaborative research, the Understanding the Relationship between Activity and Neighbourhoods (URBAN) Study seeks to overcome these limitations by determining the strengths of association between detailed measures of the neighborhood built environment with PA levels across multiple domains and body size measures in adults and children. This article outlines the research protocol developed for the URBAN Study.</p> <p>Methods and design</p> <p>The URBAN Study is a multi-centered, stratified, cross-sectional research design, collecting data across four New Zealand cities. Within each city, 12 neighborhoods were identified and selected for investigation based on higher or lower walkability and Māori demographic attributes. Neighborhoods were selected to ensure equal representation of these characteristics. Within each selected neighborhood, 42 households are being randomly selected and an adult and child (where possible) recruited into the study. Data collection includes: objective and self-reported PA engagement, neighborhood perceptions, demographics, and body size measures. The study was designed to recruit approximately 2,000 adults and 250 children into the project. Other aspects of the study include photovoice, which is a qualitative assessment of built environment features associated with PA engagement, an audit of the neighborhood streetscape environment, and an individualized neighborhood walkability profile centered on each participant's residential address. Multilevel modeling will be used to examine the individual-level and neighborhood-level relationships with PA engagement and body size.</p> <p>Discussion</p> <p>The URBAN Study is applying a novel scientifically robust research design to provide urgently needed epidemiological information regarding the associations between the built environment and health outcomes. The findings will contribute to a larger, international initiative in which similar neighborhood selection and PA measurement procedures are utilized across eight countries. Accordingly, this study directly addresses the international priority issues of increasing PA engagement and decreasing obesity levels.</p

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Neighbourhood built environment associations with body size in adults:mediating effects of activity and sedentariness in a cross-sectional study of New Zealand adults

Background: The aim of this study was to determine the associations between body size and built environment walkability variables, as well as the mediating role of physical activity and sedentary behaviours with body size. Methods: Objective environment, body size (body mass index (BMI), waist circumference (WC)), and sedentary time and physical activity data were collected from a random selection of 2033 adults aged 20-65 years living in 48 neighbourhoods across four New Zealand cities. Multilevel regression models were calculated for each comparison between body size outcome and built environment exposure. Results and Discussion: Street connectivity and neighborhood destination accessibility were significant predictors of body size (1 SDchange predicted a 1.27 to 1.41 % reduction in BMI and a 1.76 to 2.29 % reduction in WC). Significantrelationships were also observed for streetscape (1 SD change predicted a 1.33 % reduction in BMI) anddwelling density (1 SD change predicted a 1.97 % reduction in BMI). Mediation analyses revealed asignificant mediating effect of physical activity on the relationships between body size and street connectivity and neighbourhood destination accessibility (explaining between 10.4 and 14.6 % of the total effect). No significant mediating effect of sedentary behaviour was found. Findings from this cross-sectional study of a random selection of New Zealand adults are consistent with international research. Findings are limited to individual environment features only; conclusions cannot be drawn about the cumulative and combined effect of individual features on outcomes. Conclusions: Built environment features were associated with body size in the expected directions. Objectively-assessed physical activity mediated observed built environment-body size relationships