Q2Q_2-free families in the Boolean lattice

For a family $\mathcal{F}$ of subsets of [n]=\{1, 2, ..., n} ordered by inclusion, and a partially ordered set P, we say that $\mathcal{F}$ is P-free if it does not contain a subposet isomorphic to P. Let $ex(n, P)$ be the largest size of a P-free family of subsets of [n]. Let $Q_2$ be the poset with distinct elements a, b, c, d, a<b, c<d; i.e., the 2-dimensional Boolean lattice. We show that $2N -o(N) \leq ex(n, Q_2)\leq 2.283261N +o(N),$ where $N = \binom{n}{\lfloor n/2 \rfloor}$. We also prove that the largest $Q_2$-free family of subsets of [n] having at most three different sizes has at most 2.20711N members.Comment: 18 pages, 2 figure

Newly qualified physical education teachers’ experiences of developing subject knowledge prior to, during and after a Postgraduate Certificate in Education course

Office for Standards in Education (OFSTED) inspections of secondary Postgraduate Certificate in Education (PGCE) physical education courses in England between 1996 and 1998 (OFSTED, 1999) were critical of student teachers' subject knowledge. The purpose of this study was to investigate the development of subject knowledge and influences on the development of that subject knowledge in a sample of three newly qualified teachers (NQTs) who had completed a PGCE physical education course in England. The research comprised semi-structured interviews and analysis of documentation. Among these three NQTs there were some similarities, but more differences in terms of the development of subject knowledge as well as different influences on the development of subject knowledge. These results suggest that teacher educators may need to be flexible in how they approach and support the development of student teachers' subject knowledge. Results also suggest that teacher educators should work more closely with colleagues teaching sports-related undergraduate degree courses to support the development of subject knowledge for those students who wish to progress to a PGCE physical education course

Lentiviral Vector Delivery of Human Interleukin-7 (hIL-7) to Human Immune System (HIS) Mice Expands T Lymphocyte Populations

Genetically modified mice carrying engrafted human tissues provide useful models to study human cell biology in physiologically relevant contexts. However, there remain several obstacles limiting the compatibility of human cells within their mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse cytokines and human cellular receptors, depriving the graft of important survival and growth signals. To circumvent this problem, we utilized a lentivirus-based delivery system to express physiologically relevant levels of human interleukin-7 (hIL-7) in Rag2-/-γc-/- mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-γc-/- Human Immune System (HIS) mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the spleens of HIV infected HIS mice without affecting viral load. Taken together, our study unveils a versatile approach to deliver human cytokines to HIS mice, to both improve engraftment and determine the impact of cytokines on human diseases

NLTE analysis of Co I/Co II lines in spectra of cool stars with new laboratory hyperfine splitting constants

We investigate the statistical equilibrium of Co in the atmospheres of cool stars, and the influence of NLTE and HFS (hyperfine splitting) on the formation of Co lines and abundances. Significant departures from LTE level populations are found for Co I, also number densities of excited states in Co II differ from LTE at low metallicity. The NLTE abundance of Co in solar photosphere is 4.95 +/- 0.04 dex, which is in agreement with that in C I meteorites within the combined uncertainties. The spectral lines of Co I were calculated using the results of recent measurements of hyperfine interaction constants by UV Fourier transform spectrometry. For Co II, the first laboratory measurements of hyperfine structure splitting A and B factors were performed. A differential abundance analysis of Co is carried out for 18 stars in the metallicity range -3.12 < [Fe/H] < 0. The abundances are derived by method of spectrum synthesis. At low [Fe/H], NLTE abundance corrections for Co I lines are as large as +0.6 >... +0.8 dex. Thus, LTE abundances of Co in metal-poor stars are severely underestimated. The stellar NLTE abundances determined from the single UV line of Co II are lower by ~0.5-0.6 dex. The discrepancy might be attributed to possible blends that have not been accounted for in the solar Co II line and its erroneous oscillator strength. The increasing [Co/Fe] trend in metal-poor stars, as calculated from the Co I lines under NLTE, can be explained if Co is overproduced relative to Fe in massive stars. The models of galactic chemical evolution are wholly inadequate to describe this trend suggesting that the problem is in SN yields.Comment: submitted to MNRAS, 15 page

The impact of Cochrane Systematic Reviews : a mixed method evaluation of outputs from Cochrane Review Groups supported by the UK National Institute for Health Research

© 2014 Bunn et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: There has been a growing emphasis on evidence-informed decision making in health care. Systematic reviews, such as those produced by the Cochrane Collaboration, have been a key component of this movement. The UK National Institute for Health Research (NIHR) Systematic Review Programme currently supports 20 Cochrane Review Groups (CRGs). The aim of this study was to identify the impacts of Cochrane reviews published by NIHR funded CRGs during the years 2007-11. Methods: We sent questionnaires to CRGs and review authors, interviewed guideline developers and used bibliometrics and documentary review to get an overview of CRG impact and to evaluate the impact of a sample of 60 Cochrane reviews. We used a framework with four categories (knowledge production, research targeting, informing policy development, and impact on practice/services). Results: A total of 1502 new and updated reviews were produced by the 20 NIHR funded CRGs between 2007-11. The clearest impacts were on policy with a total of 483 systematic reviews cited in 247 sets of guidance; 62 were international, 175 national (87 from the UK) and 10 local. Review authors and CRGs provided some examples of impact on practice or services, for example safer use of medication, the identification of new effective drugs or treatments and potential economic benefits through the reduction in the use of unproven or unnecessary procedures. However, such impacts are difficult to objectively document and the majority of reviewers were unsure if their review had produced specific impacts. Qualitative data suggested that Cochrane reviews often play an instrumental role in informing guidance although a poor fit with guideline scope or methods, reviews being out of date and a lack of communication between CRGs and guideline developers were barriers to their use. Conclusions: Health and economic impacts of research are generally difficult to measure. We found that to be the case with this evaluation. Impacts on knowledge production and clinical guidance were easier to identify and substantiate than those on clinical practice. Questions remain about how we define and measure impact and more work is needed to develop suitable methods for impact analysis.Peer reviewe

Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents

Impact of monopolar radiofrequency energy on subchondral bone viability

The purpose of this study was to analyze the impact of monopolar radiofrequency energy treatment on subchondral bone viability. The femoral grooves of six chinchilla bastard rabbits were exposed bilaterally to monopolar radiofrequency energy for 2, 4 and 8 s, creating a total of 36 defects. An intravital fluorescence bone-labeling technique characterized the process of subchondral bone mineralization within the 3 months following exposure to radiofrequency energy and was analyzed by widefield epifluorescence optical sectioning microscopy using an ApoTome. After 2 s of radiofrequency energy exposure, regular fluorescence staining of the subchondral bone was evident in all samples when compared to untreated areas. The depth of osteonecrosis after 4 and 8 s of radiofrequency energy treatment averaged 126 and 942 µm at 22 days (P < .05; P < .01). The 4 s treatment group showed no osteonecrosis after 44 days whereas the depth of osteonecrosis extended from 519 µm at 44 days (P < .01), to 281 µm at 66 days (P < .01) and to 133 µm at 88 days (P < .05) after 8 s of radiofrequency energy application. Though radiofrequency energy may induce transient osteonecrosis in the superficial zone of the subchondral bone, the results of this study suggest that post-arthroscopic osteonecrosis appears to be of only modest risk given the current clinical application in humans

Metabolic profiles of socioeconomic position: a multi-cohort analysis

Background Low socioeconomic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. Methods We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles, in approximately 30,000 adults and 4,000 children across ten UK and Finnish cohort studies. Results In risk factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents), and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared to non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. Conclusions Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavorable metabolic profile, consistent across ages and cohorts. The metabolites we found associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities

Metabolic profiles of socio-economic position: a multi-cohort analysis

Background: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. Methods: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in 30 000 adults and 4000 children across 10 UK and Finnish cohort studies. Results: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. Conclusions: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities

Evolutionary Constraint Helps Unmask a Splicing Regulatory Region in BRCA1 Exon 11

BACKGROUND: Alternative splicing across exon 11 produces several BRCA1 isoforms. Their proportion varies during the cell cycle, between tissues and in cancer suggesting functional importance of BRCA1 splicing regulation around this exon. Although the regulatory elements driving exon 11 splicing have never been identified, a selective constraint against synonymous substitutions (silent nucleotide variations that do not alter the amino acid residue sequence) in a critical region of BRCA1 exon 11 has been reported to be associated with the necessity to maintain regulatory sequences. METHODOLOGY/PRINCIPAL FINDINGS: Here we have designed a specific minigene to investigate the possibility that this bias in synonymous codon usage reflects the need to preserve the BRCA1 alternative splicing program. We report that in-frame deletions and translationally silent nucleotide substitutions in the critical region affect splicing regulation of BRCA1 exon 11. CONCLUSIONS/SIGNIFICANCE: Using a hybrid minigene approach, we have experimentally validated the hypothesis that the need to maintain correct alternative splicing is a selective pressure against translationally silent sequence variations in the critical region of BRCA1 exon 11. Identification of the trans-acting factors involved in regulating exon 11 alternative splicing will be important in understanding BRCA1-associated tumorigenesis