Stem cells in human oral epithelium

The stratifying epithelia of skin and mucosa continuously renew their structure by cell division, but only a small fraction of proliferative cells, the stem cells, are capable of continuous self-renewal. The staining distribution of various stem cell and differentiation markers were investigated in normal human mucosal epithelium. To determine the extent of regional variation in patterns of stem cell behaviour in human epithelia, human mucosal keratinocytes were amplified in vitro. Using retroviral vectors, a sub-population of these cells were transduced with genes for histochemically detectable markers to permit lineage analyses. Organotypic culture methods were used to generate epithelia with normal patterns of cell kinetics and differentiation and these were examined after maintenance in vitro or after transplantation back to in vivo sites in immune deficient mice. The clonal lineages resulting from stem cell patterns were compared and the number of functional stem cells were assessed from the size of stable clonal units regenerated. The cell cycles of keratinocytes grown on plastic compared to organotypic culture were also investigated by flow cytometry to see if the organotypic cultures provided a suitable stem cell model. Results included the following. Antibody staining in palate revealed that K15 and K19 identified zones of positively stained basal cells at the epithelial rete tips. These K15 and K19 positive regions were negative for differentiation markers K6 and K16, indicating that cells in these regions were undifferentiated and could include stem cells Organotypic cultures gave similar staining profiles to palate, and using retrovirally stained subpopulations of cells and transplantation to SCID mice, clonal units were identified which did not correspond to the primitive rete that had reformed. Flow cytometry work showed that the cell cycles of cells grown in vitro on plastic were faster than the cell cycles of organotypic cultures

Psychosocial and Physiological Factors Affecting Selection to Regional Age-Grade Rugby Union Squads: A Machine Learning Approach

Talent selection programmes choose athletes for talent development pathways. Currently, the set of psychosocial variables that determine talent selection in youth Rugby Union are unknown, with the literature almost exclusively focusing on physiological variables. The purpose of this study was to use a novel machine learning approach to identify the physiological and psychosocial models that predict selection to a regional age-grade rugby union team. Age-grade club rugby players (n = 104; age, 15.47 ± 0.80; U16, n = 62; U18, n = 42) were assessed for physiological and psychosocial factors during regional talent selection days. Predictive models (selected vs. non-selected) were created for forwards, backs, and across all players using Bayesian machine learning. The generated physiological models correctly classified 67.55% of all players, 70.09% of forwards, and 62.50% of backs. Greater hand-grip strength, faster 10 m and 40 m sprint, and power were common features for selection. The generated psychosocial models correctly classified 62.26% of all players, 73.66% of forwards, and 60.42% of backs. Reduced burnout, reduced emotional exhaustion, and lower reduced sense of accomplishment, were common features for selection. Selection appears to be predominantly based on greater strength, speed, and power, as well as lower athlete burnout

The Family Nurse Partnership to reduce maltreatment and improve child health and development in young children: the BB:2 6 routine data-linkage follow-up to earlier RCT

Background The short-term effectiveness (to 24 months post partum) of a preventative home-visiting intervention, the Family Nurse Partnership, was previously assessed in the Building Blocks trial (BB:0–2). Objectives The objectives were to establish the medium-term effectiveness of the Family Nurse Partnership in reducing maltreatment and improving maternal health (second pregnancies) and child health, developmental and educational outcomes (e.g. early educational attendance, school readiness); to explore effect moderators and mediators; and to describe the costs of enhancing usually provided health and social care with the Family Nurse Partnership. Design Children and their mothers from an existing trial cohort were followed up using routine data until the child was 7 years of age. Setting This study was set in 18 partnerships between local authorities and health-care organisations in England. Participants The participants were mothers [and their firstborn child(ren)] recruited as pregnant women aged ≤ 19 years, in local authority Family Nurse Partnership catchment areas, at < 25 weeks’ gestation, able to provide consent and able to converse in English. Participants mandatorily withdrawn (e.g. owing to miscarriage) from the BB:0–2 trial were excluded. Interventions The intervention comprised up to a maximum of 64 home visits by specially trained family nurses from early pregnancy until the firstborn child was 2 years of age, plus usually provided health and social care support. The comparator was usual care alone. Main outcome measures The primary outcome measure was child-in-need status recorded at any time during follow-up. The secondary outcomes were as follows: (1) referral to social services, child protection registration (plan), child-in-need categorisation, looked-after status, recorded injuries and ingestions at any time during follow-up; (2) early child care and educational attendance, school readiness (Early Years Foundation Stage Profile score) and attainment at Key Stage 1; and (3) health-care costs. Data sources The following data sources were used: maternally reported baseline and follow-up data (BB:0–2), Hospital Episode Statistics data (NHS Digital), social care and educational data (National Pupil Database) and abortions data (Department of Health and Social Care). Results There were no differences between study arms in the rates of referral to social services, being registered as a child in need, receiving child protection plans, entering care or timing of first referral for children subsequently assessed as in need. There were no differences between study arms in rates of hospital emergency attendance, admission for injuries or ingestions, or in duration of stay for admitted children. Children in the Family Nurse Partnership arm were more likely to achieve a good level of development at reception age (school readiness), an effect strengthened when adjusting for birth month. Differences at Key Stage 1 were not statistically different, but, after adjusting for birth month, children in the Family Nurse Partnership arm were more likely to reach the expected standard in reading. Programme effects were greater for boys (Key Stage 1: writing); children of younger mothers (Key Stage 1: writing, Key Stage 1: mathematics); and children of mothers not in employment, education or training at study baseline (Key Stage 1: writing). There were no differences between families who were part of the Family Nurse Partnership and those who were not for any other outcome. The differences between study arms in resource use and costs were negligible

Healthy eating and lifestyle in pregnancy (HELP): a cluster randomised trial to evaluate the effectiveness of a weight management intervention for pregnant women with obesity on weight at 12 months postpartum

Objective: To assess whether a weight management intervention for pregnant women with obesity was effective in reducing body mass index (BMI) 12 months after giving birth. Methods: Pragmatic, cluster randomised controlled trial (RCT) with embedded cost-effectiveness analysis. 598 women with a BMI of ≥30 kg/m2 (between 12 and 20 weeks gestation) were recruited from 20 secondary care maternity units in England and Wales. BMI at 12 months postpartum was the primary outcome. A range of clinical and behavioural secondary outcomes were examined. Interventions: Women attending maternity units randomised to intervention were invited to a weekly weight management group, which combined expertise from a commercial weight loss programme with clinical advice from midwives. Both intervention and control participants received usual care and leaflets on diet and physical activity in pregnancy. Results: Mean (SD) BMI at 12 months postpartum was 36.0 kg/m2 (5.2) in the control group, and 37.5 kg/m2 (6.7) in the intervention group. After adjustment for baseline BMI, the intervention effect was −0.02 (95% CI −0.04 to 0.01). The intervention group had an improved healthy eating score (3.08, 95% CI 0.16 to 6.00, p < 0.04), improved fibre score (3.22, 1.07 to 5.37, p < 0.01) and lower levels of risky drinking at 12 months postpartum compared to the control group (OR 0.45, 0.27 to 0.74, p < 0.002). The net incremental monetary benefit was not statistically significantly different between arms, although the probability of the intervention being cost-effective was above 60%, at policy-relevant thresholds. Conclusions: There was no significant difference between groups on the primary outcome of BMI at 12 months. Analyses of secondary outcomes indicated improved healthy eating and lower levels of risky drinking. Trial registration: Current Controlled Trials ISRCTN25260464

A nurse-led home-visitation programme for first-time mothers in reducing maltreatment and improving child health and development (BB:2-6): longer-term outcomes from a randomised cohort using data-linkage

Objectives Measure effectiveness of family nurse partnership (FNP) home-visiting programme in reducing maltreatment and improving maternal health and child health, developmental and educational outcomes; explore effect moderators, mediators; describe costs. Design Follow-up of BB:0–2 trial cohort (ISRCTN:23019866) up to age 7 years in England using record linkage. Participants 1618 mothers aged 19 years or younger and their firstborn child(ren) recruited to BB:0–2 trial at less than 25 weeks gestation and not mandatorily withdrawn from trial or opted out. Intervention families were offered up to a maximum of 64 home visits by specially trained nurses from pregnancy until firstborn child was 2 years old, plus usually provided health and social care support. Comparator was usual care alone. Outcome measures Primary outcome: state-verified child-in-need status recorded at any time during follow-up. Secondary outcomes: referral to social services, child protection registration (plan), child-in-need categorisation, looked-after status, recorded injuries and ingestions any time during follow-up, early childcare and educational attendance, school readiness and attainment at key stage 1 (KS1), healthcare costs. Results Match rates for 1547 eligible children (1517 singletons, 15 sets of twins) were 98.3% (NHS Digital) and 97.4% (National Pupil Database). There was no difference between study arms in the proportion of children being registered as in need (adjusted OR 0.98, 95% CI 0.74 to 1.31), or for any other measure of maltreatment. Children in the FNP arm were more likely to achieve a good level of development at reception age (school readiness) (adjusted OR 1.24, 95% CI 1.01 to 1.52). After adjusting for birth month, children in FNP arm were more likely to reach the expected standard in reading at KS1 (adjusted OR 1.26, 95% CI 1.02 to 1.57). We found no trial arm differences for resource use and costs. Conclusions FNP did not improve maltreatment or maternal outcomes. There was evidence of small advantages in school readiness and attainment at KS1

Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks):a pragmatic randomised controlled trial

SummaryBackgroundMany countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth.MethodsWe did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866.FindingsBetween June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64–1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI −47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99–1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77–1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother–child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention.InterpretationAdding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge.FundingDepartment of Health Policy Research Programme