FSH treatment improves sperm DNA damage in men with idiopathic infertility carriers of the FSH receptor p.N680S homozygous N genotype: an interim analysis

Study question: To assess whether in men with idiopathic infertility, the sperm DNA fragmentation (sDF) improves depending on the FSH receptor (FSHR) genotype as assessed by the non-synonymous polymorphisms (SNP) rs6166 (wild type or p.N680S). Summary answer: FSH treatment improves sDF in a subgroup of idiopathic infertile men, although 40% of these men do not show any significant improve- ment. The response of sDF, a surrogate marker of sperm quality, together with the evaluation of FSHR SNP p.N680S might be useful to predict the response to FSH treatment. What is known already: FSH is fundamental for spermatogenesis and is em- pirically used to treat male idiopathic infertility. Several studies suggest that sDF could be a candidate predictor of response to FSH treatment, in terms of probability to conceive. Furthermore, it is widely accepted that the FSHR SNP p.N680S influences ovarian response in women and testicular volume in men. Study design, size, duration: Multicenter, longitudinal, prospective, open-la- bel, two-arms clinical trial. Subjects enrolled were idiopathic infertile men and received 150 IU of recombinant FSH (Gonal f®) every other day for 12 weeks and were then followed-up for further 12 weeks after FSH-withdrawal. Patients were evaluated at baseline and at the end of the two phases. Participants/materials, setting, methods: Eighty-eight men with idiopathic male infertility carrier of the homozygous FSHR p.N680S N or S genotype, FSH 15%, were enrolled. 66 patients completed the sDF analysis. sDF was centrally evaluated by TUNEL/PI assay coupled to flow cy- tometry, resolving two different sperm populations, namely: PIbrighter and PIdimmer. Main results and the role of chance: Thirty-seven men (56%) were carriers of the p.N680S homozygous-N and 29 (44%) of the homozygous-S genotype, respectively. Total sDF (PIbrighter + PIdimmer) was significantly lower at the end of the study in patients carriers of the p.N680S-N allele than patients carri- ers of p.N680S-S allele (p = 0.008). Only in patients carriers of the p.N680S-N allele, total sDF decreased significantly from baseline to the end of the study (p = 0.021) and this decrease was entirely sustained by the sperm population containing vital sperms (i.e., PIbrighter fraction) (p = 0.008). PIdimmer frac- tion, including only non-vital sperms, was significantly higher in patients car- riers of the p.N680S-S allele than in carriers of N allele (p = 0.018). Total sDF was inversely related to total sperm number (p = 0.020) and progressive sperm motility (p = 0.014). Limitations, reason for caution: The statistical power of the results obtained so far is 86.9%, with alpha-error 0.05. This is an interim-analysis. Wider implications of the findings: The study suggests that FSH treatment induces a significant improvement of total sDF in men carriers of the p.N680S homozygous N allele. This sDF decrease awaits confirmation, since the study will be completed by June 2015. Study funding/competing interest(s): Funding by commercial/corporate company(ies) – The study was supported by unrestricted grant by Merck Serono. Trial registration number: EudraCT number 2010-020240-35. Keywords: FSH treatment, male infertility, Sperm-DNA fragmentatio

Seeking children's perspectives: a respectful layered research approach

This article discusses why researchers and educators might choose to seek children's perspectives. It also highlights some of the key considerations when seeing children as having the right to contribute to decisions that affect them. The article draws on findings from a study that used pedagogically oriented methods for researching three- and four-year-old children's perspectives about outdoor spaces in the early childhood setting they attended. The article discusses the possibilities and practicalities of this research approach for both research and pedagogy. Examples are provided for others who may be considering working/researching in these ways

Assessing implementation difficulties in tobacco use prevention and cessation counselling among dental providers

<p>Abstract</p> <p>Background</p> <p>Tobacco use adversely affects oral health. Clinical guidelines recommend that dental providers promote tobacco abstinence and provide patients who use tobacco with brief tobacco use cessation counselling. Research shows that these guidelines are seldom implemented, however. To improve guideline adherence and to develop effective interventions, it is essential to understand provider behaviour and challenges to implementation. This study aimed to develop a theoretically informed measure for assessing among dental providers implementation difficulties related to tobacco use prevention and cessation (TUPAC) counselling guidelines, to evaluate those difficulties among a sample of dental providers, and to investigate a possible underlying structure of applied theoretical domains.</p> <p>Methods</p> <p>A 35-item questionnaire was developed based on key theoretical domains relevant to the implementation behaviours of healthcare providers. Specific items were drawn mostly from the literature on TUPAC counselling studies of healthcare providers. The data were collected from dentists (n = 73) and dental hygienists (n = 22) in 36 dental clinics in Finland using a web-based survey. Of 95 providers, 73 participated (76.8%). We used Cronbach's alpha to ascertain the internal consistency of the questionnaire. Mean domain scores were calculated to assess different aspects of implementation difficulties and exploratory factor analysis to assess the theoretical domain structure. The authors agreed on the labels assigned to the factors on the basis of their component domains and the broader behavioural and theoretical literature.</p> <p>Results</p> <p>Internal consistency values for theoretical domains varied from 0.50 ('emotion') to 0.71 ('environmental context and resources'). The domain environmental context and resources had the lowest mean score (21.3%; 95% confidence interval [CI], 17.2 to 25.4) and was identified as a potential implementation difficulty. The domain emotion provided the highest mean score (60%; 95% CI, 55.0 to 65.0). Three factors were extracted that explain 70.8% of the variance: motivation (47.6% of variance, α = 0.86), capability (13.3% of variance, α = 0.83), and opportunity (10.0% of variance, α = 0.71).</p> <p>Conclusions</p> <p>This study demonstrated a theoretically informed approach to identifying possible implementation difficulties in TUPAC counselling among dental providers. This approach provides a method for moving from diagnosing implementation difficulties to designing and evaluating interventions.</p

Assessing implementation difficulties in tobacco use prevention and cessation counselling among dental providers

Background: Tobacco use adversely affects oral health. Clinical guidelines recommend that dental providers promote tobacco abstinence and provide patients who use tobacco with brief tobacco use cessation counselling. Research shows that these guidelines are seldom implemented, however. To improve guideline adherence and to develop effective interventions, it is essential to understand provider behaviour and challenges to implementation. This study aimed to develop a theoretically informed measure for assessing among dental providers implementation difficulties related to tobacco use prevention and cessation (TUPAC) counselling guidelines, to evaluate those difficulties among a sample of dental providers, and to investigate a possible underlying structure of applied theoretical domains.Methods: A 35-item questionnaire was developed based on key theoretical domains relevant to the implementation behaviours of healthcare providers. Specific items were drawn mostly from the literature on TUPAC counselling studies of healthcare providers. The data were collected from dentists (n = 73) and dental hygienists (n = 22) in 36 dental clinics in Finland using a web-based survey. Of 95 providers, 73 participated (76.8%). We used Cronbach's alpha to ascertain the internal consistency of the questionnaire. Mean domain scores were calculated to assess different aspects of implementation difficulties and exploratory factor analysis to assess the theoretical domain structure. The authors agreed on the labels assigned to the factors on the basis of their component domains and the broader behavioural and theoretical literature.Results: Internal consistency values for theoretical domains varied from 0.50 ('emotion') to 0.71 ('environmental context and resources'). The domain environmental context and resources had the lowest mean score (21.3%; 95% confidence interval [CI], 17.2 to 25.4) and was identified as a potential implementation difficulty. The domain emotion provided the highest mean score (60%; 95% CI, 55.0 to 65.0). Three factors were extracted that explain 70.8% of the variance: motivation (47.6% of variance, alpha = 0.86), capability (13.3% of variance, alpha = 0.83), and opportunity (10.0% of variance, alpha = 0.71).Conclusions: This study demonstrated a theoretically informed approach to identifying possible implementation difficulties in TUPAC counselling among dental providers. This approach provides a method for moving from diagnosing implementation difficulties to designing and evaluating interventions

Aboriginal Children and Their Caregivers Living with Low Income: Outcomes from a Two-Generation Preschool Program

The development of preschool children of Aboriginal heritage is jeopardized by the inter-generational transmission of risk that has created, and continues to create, social disadvantage. Early intervention programs are intended to mitigate the impact of social disadvantage. Yet, evidence of the effectiveness of these programs for children of Aboriginal heritage is limited. The purpose of this study was to examine the effects of a two-generation, multi-cultural preschool program on 45 children of Aboriginal heritage and their caregivers. We used a single-group, pretest (program intake)/posttest (program exit) design with follow-up when the children were 7 years old. We used an observational measure of child receptive language (Peabody Picture Vocabulary Test–III) and caregiver-reported measures of child development (Nipissing District Developmental Screen), risk for child maltreatment (Adult-Adolescent Parenting Inventory; AAPI), parenting stress (Parenting Stress Index; PSI), self-esteem (Rosenberg Self-Esteem scale; RSE), and life skills (Community Life Skills scale; CLS). Using paired t-tests we found statistically significant increases in child receptive language scores between intake and exit, and repeated-measures ANOVA showed that these improvements were maintained up to age 7 years. For caregivers, Pearson’s correlations demonstrated that risk for child maltreatment, parenting stress, self-esteem, and life skills were stable over time. Results of this study suggest that children of Aboriginal heritage can benefit from participation in a two-generation, multi-cultural preschool program. Their caregivers may have received greater benefit if issues of intergenerational transmission of the negative influences of residential schools were addressed as part of programming

Early childhood pedagogies: spaces for young children to flourish

This paper introduces the Special Issue of Early Child Development and Care focused on Early Childhood Pedagogy. It opens by considering past and present discourses concerning early childhood pedagogy, and focus is given to established philosophical underpinnings in the field and their translation to contemporary guidance, alongside research and policy. It is argued that early childhood pedagogy is a contested, complex and diverse space, yet these factors are entirely appropriate for supporting young children to flourish as valued individuals in different contexts. Building on this argument, it is posited that it may be more appropriate to discuss early childhood pedagogies rather than early childhood pedagogy. The paper goes on to critique a range of established early childhood pedagogies, before introducing 18 papers from across the world that make exciting new contributions to the discourse. It is intended that this collection will inspire new debates and fresh endeavours concerning early childhood pedagogies

Effects of backpacking holidays in Australia on alcohol, tobacco and drug use of UK residents

BACKGROUND: Whilst alcohol and drug use among young people is known to escalate during short holidays and working breaks in international nightlife resorts, little empirical data are available on the impact of longer backpacking holidays on substance use. Here we examine changes in alcohol, tobacco and drug use when UK residents go backpacking in Australia. METHODS: Matched information on alcohol and drug use in Australia and the UK was collected through a cross sectional cohort study of 1008 UK nationals aged 18–35 years, holidaying in Sydney or Cairns, Australia, during 2005. RESULTS: The use of alcohol and other drugs by UK backpackers visiting Australia was common with use of illicit drugs being substantially higher than in peers of the same age in their home country. Individuals showed a significant increase in frequency of alcohol consumption in Australia compared to their behaviour in the UK with the proportion drinking five or more times per week rising from 20.7% (UK) to 40.3% (Australia). Relatively few individuals were recruited into drug use in Australia (3.0%, cannabis; 2.7% ecstasy; 0.7%, methamphetamine). However, over half of the sample (55.0%) used at least one illicit drug when backpacking. Risk factors for illicit drug use while backpacking were being regular club goers, being male, Sydney based, travelling without a partner or spouse, having been in Australia more than four weeks, Australia being the only destination on their vacation and drinking or smoking five or more days a week. CONCLUSION: As countries actively seek to attract more international backpacker tourists, interventions must be developed that target this population's risk behaviours. Developing messages on drunkenness and other drug use specifically for backpackers could help minimise their health risks directly (e.g. adverse drug reactions) and indirectly (e.g. accidents and violence) as well as negative impacts on the host country

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Measurement of ϒ production in pp collisions at √s = 2.76 TeV

The production of ϒ(1S), ϒ(2S) and ϒ(3S) mesons decaying into the dimuon final state is studied with the LHCb detector using a data sample corresponding to an integrated luminosity of 3.3 pb−1 collected in proton–proton collisions at a centre-of-mass energy of √s = 2.76 TeV. The differential production cross-sections times dimuon branching fractions are measured as functions of the ϒ transverse momentum and rapidity, over the ranges pT &#60; 15 GeV/c and 2.0 &#60; y &#60; 4.5. The total cross-sections in this kinematic region, assuming unpolarised production, are measured to be σ (pp → ϒ(1S)X) × B ϒ(1S)→μ+μ− = 1.111 ± 0.043 ± 0.044 nb, σ (pp → ϒ(2S)X) × B ϒ(2S)→μ+μ− = 0.264 ± 0.023 ± 0.011 nb, σ (pp → ϒ(3S)X) × B ϒ(3S)→μ+μ− = 0.159 ± 0.020 ± 0.007 nb, where the first uncertainty is statistical and the second systematic