Evidence-based decision-making in a climate of political expediency: insights from local government.

AIMS: Local authorities in England are responsible for public health and health promotion. This article sought to explore how research and decision-making co-exist in a local authority in England. METHODS: An Embedded Researcher was based within the local authority and used qualitative methodology to address the research aim. Interviews and focus groups were employed to ascertain a range of stakeholder views in the local authority. All transcripts were coded on NVivo 12 by the Embedded Researcher and two members of the research team cross-checked a sample for coding accuracy. Data were analysed using framework analysis. RESULTS: The data suggest several barriers to using research to inform decision-making in health promotion and public health. The study shows that research is valued in local authorities, but not always privileged - this is due to cultural factors and practical political reasons which often means that decisions need to be made expediently. Participants outlined a juxtaposition between academic credibility; timeliness to complete the research and the financial cost associated with it; against the independence and credibility that independent academics could bring. CONCLUSION: Policy formulation and delivery is an integral aspect of health promotion and critical to achieving improved population health and reductions in health inequalities. However, there exists tensions between gathering research evidence and making research-informed decisions. The article concludes by advocating the use of Embedded Researchers to fully understand how research is gathered and used to support public health and health promotion policymaking.

Learning from the challenges of undertaking an evaluation of a multi-partner housing support initiative delivered within a hospital setting.

Objectives: We present learning from a mixed-methods evaluation of a housing support initiative for hospital inpatients. Study design: A mixed-methods process evaluation. Methods: A social housing provider delivered a housing support service in two hospitals (mental health unit and general hospital). Healthcare providers, the social housing provider and academic researchers designed and undertook a co-produced, mixed-methods process evaluation of the intervention. The evaluation included questionnaires, semi-structured interviews, analysis of routinely collected data and economic analysis. Despite commitment from the partners, the evaluation faced challenges. We reflect on the lessons learnt within our discussion paper. Results: Despite the commitment of the partners, we faced several challenges.We took an iterative approach to the design and processes of the evaluation to respond to arising challenges. Recruitment of service-users was more difficult than anticipated, requiring additional staff resources. Given the small-scale nature of the intervention, and the quality of data recorded in hospital records, the planned economic analysis was not feasible. Positive factors facilitating evaluation included involvement of staff delivering the intervention, as well as managers. Being able to offer payment to partner organisations for staff time also facilitated ongoing engagement. Conclusions: Multi-partner evaluations are useful, however, researchers and partners need to be prepared to take an iterative, resource intensive approach. Both availability and quality of routine data, and the resources required to support data collection, may limit feasibility of specific methods when evaluating small-scale cross-sector initiatives. Thus, this necessitates a flexible approach to design and analysis.

Recombination Rate Variation, Hitchhiking, and Demographic History Shape Deleterious Load in Poplar.

Deleterious alleles are expected to be purged by purifying selection or maintained at low frequency. However, many additional evolutionary forces may shape the pattern of deleterious mutations across the genome and among populations, including selection, hitchhiking, recombination, and demographic history. We used exome capture data to estimate the genome-wide distribution of deleterious alleles across natural populations of the model tree black cottonwood (Populus trichocarpa). Although deleterious alleles were on average present at low frequency suggesting purifying selection, they were preferentially enriched both within genomic regions of low-recombination and in regions showing evidence of positive selection. The demographic history of this species also appeared to play a role in the distribution of deleterious alleles among populations, with peripheral populations having higher rates of deleterious homozygosity. This be due to less efficient selection arising from smaller effective population sizes at the edges of the range, and possibly also due to recent bottlenecks associated with postglacial recolonization. Finally, correlations between deleterious homozygosity and plant growth suggest a significant effect of deleterious load on fitness. Our results show that both genomic context and historical demography play a role in shaping the distribution of deleterious alleles across the genome and range of P. trichocarpa.

Exome capture from the spruce and pine giga-genomes.

Sequence capture is a flexible tool for generating reduced representation libraries, particularly in species with massive genomes. We used an exome capture approach to sequence the gene space of two of the dominant species in Canadian boreal and montane forests - interior spruce (Picea glauca x engelmanii) and lodgepole pine (Pinus contorta). Transcriptome data generated with RNA-seq were coupled with draft genome sequences to design baits corresponding to 26 824 genes from pine and 28 649 genes from spruce. A total of 579 samples for spruce and 631 samples for pine were included, as well as two pine congeners and six spruce congeners. More than 50% of targeted regions were sequenced at >10× depth in each species, while ~12% captured near-target regions within 500 bp of a bait position were sequenced to a depth >10×. Much of our read data arose from off-target regions, which was likely due to the fragmented and incomplete nature of the draft genome assemblies. Capture in general was successful for the related species, suggesting that baits designed for a single species are likely to successfully capture sequences from congeners. From these data, we called approximately 10 million SNPs and INDELs in each species from coding regions, introns, untranslated and flanking regions, as well as from the intergenic space. Our study demonstrates the utility of sequence capture for resequencing in complex conifer genomes, suggests guidelines for improving capture efficiency and provides a rich resource of genetic variants for studies of selection and local adaptation in these species.

Use of a direct-fed microbial product as a supplement during the transition period in dairy cattle.

Two studies were conducted. The objective of the first study was to assess the effects of a direct-fed microbial (DFM) product on dry matter intake, milk yield, milk components, disease incidence, and blood metabolites in dairy cattle. The objective of the second study was to assess the effects of DFM on apparent total-tract nutrient digestibility (ATTD). One hundred twenty primiparous and multiparous Holstein cows housed in a tiestall facility at the University of Guelph were used in study 1, and a subset (21) of the same cows participated in study 2. Cows were blocked by anticipated calving date (6 blocks) and then randomly assigned within parity to receive either a DFM supplement (Chr. Hansen Ltd., Milwaukee, WI) or placebo (control). The DFM supplement provided cows with 5.0 × 10(9) cfu/d of 3 strains of Enterococcus faecium and 2.0 × 10(9) cfu/d of Saccharomyces cerevisiae. The DFM supplement was mixed with 0.5 kg of ground dry corn and top-dressed during the morning feeding. The placebo supplement contained the corn only. Individual feed intakes and milk yields were recorded daily. The experiment commenced 3 wk before calving and ended 10 wk postcalving. Milk samples for component analysis were collected on 3 d per week and pooled by week. Body weights and body condition scores were assessed 1 d before enrollment in the study (wk -3), postcalving (wk 1), and at the end of wk 3, 6, and 9. Blood samples were collected before calving (wk -3) and the end of wk 1 and 3. Study 1 showed that treatment had no effect on average dry matter intake or milk yield (kg/d) over the duration of the experiment. The changes in body weights and body condition scores and net energy balance over the duration of the experiment did not differ due to treatment. Treatment had no effect on plasma concentrations of ß-hydroxybutyrate, nonesterified fatty acids, glucose, or haptoglobin. Study 2 investigated the effects of DFM on ATTD of starch and neutral detergent fiber (NDF) using insoluble NDF and lignin as internal markers. Study 2 used 21 cows (block 6) from the cows that participated in study 1 while the cows were between 60 and 70 d in milk. Cows receiving DFM had lower fecal starch content (0.88 ± 0.10 vs. 1.39 ± 0.25) and greater ATTD for starch (98.76% ± 0.28 vs. 97.87% ± 0.24) compared with those receiving placebo, and the AATD of NDF did not differ. Additionally, we detected no difference between internal markers for the measurement of ATTD. In conclusion, we were unable to detect a change in overall dry matter intake, milk yield, or milk and blood parameters with DFM supplementation. However, our results demonstrated that DFM can have a positive effect on total-tract starch digestibility. More studies are needed to investigate the effects of DFM and their modes of action under multiple management conditions.

Exome resequencing reveals signatures of demographic and adaptive processes across the genome and range of black cottonwood (Populus trichocarpa).

Extant variation in temperate and boreal plant species has been influenced by both demographic histories associated with Pleistocene glacial cycles and adaptation to local climate. We used sequence capture to investigate the role of these neutral and adaptive processes in shaping diversity in black cottonwood (Populus trichocarpa). Nucleotide diversity and Tajima's D were lowest at replacement sites and highest at intergenic sites, while LD showed the opposite pattern. With samples grouped into three populations arrayed latitudinally, effective population size was highest in the north, followed by south and centre, and LD was highest in the south followed by the north and centre, suggesting a possible northern glacial refuge. FST outlier analysis revealed that promoter, 5'-UTR and intronic sites were enriched for outliers compared with coding regions, while no outliers were found among intergenic sites. Codon usage bias was evident, and genes with synonymous outliers had 30% higher average expression compared with genes containing replacement outliers. These results suggest divergent selection related to regulation of gene expression is important to local adaptation in P. trichocarpa. Finally, within-population selective sweeps were much more pronounced in the central population than in putative northern and southern refugia, which may reflect the different demographic histories of the populations and concomitant effects on signatures of genetic hitchhiking from standing variation.

A Novel Spore Collection Device for Sampling Exposure Pathways: A Case Study of Puccinia psidii.

A device comprising a filter attached to a vacuum cleaner was purpose-built to sample rust spores from three potentially high-risk pathways in Australia: passengers, fresh flowers, and sea cargo. The proportion of spores recovered from eight surfaces comparable with those on each pathway (cotton, denim, roses, carnations, chrysanthemums, wood, plastic, and metal) was estimated in the laboratory. Spore recovery percentages were highest for denim clothing (61% Puccinia triticina Erikss. and 62% Uromycladium tepperianum) and lowest for carnations (4% P. triticina Erikss. and 5% U. tepperianum). Subsequently, the device was tested at several locations on the Central Coast of New South Wales, Australia, recently affected by a "myrtle rust" outbreak. Symptomatic and asymptomatic myrtle rust hosts, myrtle rust nonhosts, and inanimate objects (e.g., clothing and vehicles) were sampled in conjunction with the emergency response to the outbreak. A polymerase chain reaction (PCR) assay developed for P. psidii established the presence of myrtle rust, and visual inspections provided spore count estimations. All samples from symptomatic myrtle rust hosts produced positive PCR results and spore count estimations were generally much greater. Several samples from asymptomatic myrtle rust hosts, myrtle rust nonhosts, and inanimate objects also produced positive PCR results; however, there were discrepancies between PCR results and spore count estimations in some of these samples, all of which had <100 spores. This study highlights the utility of the device and analytical methodology, especially during the early stages of a disease outbreak when infection symptoms on plants and contamination on objects is not visible upon gross examination.

Postglacial history of a widespread conifer produces inverse clines in selective neutrality tests.

Deviations of the site frequency spectrum of mutations (SFS) from neutral expectations may be caused by natural selection or by demographic processes such as population subdivision or temporal changes in population size. As most widespread temperate and boreal tree species have expanded from glacial refugia in the past 13,000 years, colonization bottlenecks associated with this migration may have left variable demographic signatures among geographic populations corresponding to distance from the refugia. To determine whether the signature of postglacial re-colonization has skewed the SFS in the widely distributed conifer Sitka spruce (Picea sitchensis (Bong.) Carr.), we re-sequenced 153 nuclear genes in six populations from across the species range. We found that while the SFS for the pooled sample produced negative values for Tajima's D and Fay and Wu's H, these statistics exhibited strong clinal variation when populations were analysed separately (R(2) = 0.84, P = 0.007 for Tajima's D and R(2) = 0.65, P = 0.033 for Fay and Wu's H). When historical bottlenecks of varying age were simulated using approximate Bayesian computation, distance of populations from the southern range limit explained most of the variation in bottleneck timing among populations (R(2) = 0.89, P = 0.003). These data suggest that sequential population bottlenecks during postglacial re-colonization have resulted in diverse among-population signatures within the contemporary SFS in Sitka spruce, with rare variants more common in the south, and medium-frequency variants more common in the north. Our results also emphasize the need to consider sampling strategy and to explore population-specific null demographic models in surveys of nucleotide variation in widely distributed species.

An informal school-based peer-led intervention for smoking prevention in adolescence (ASSIST): a cluster randomised trial.

BACKGROUND: Schools in many countries undertake programmes for smoking prevention, but systematic reviews have shown mixed evidence of their effectiveness. Most peer-led approaches have been classroom-based, and rigorous assessments are scarce. We assessed the effectiveness of a peer-led intervention that aimed to prevent smoking uptake in secondary schools. METHODS: We undertook a cluster randomised controlled trial of 10 730 students aged 12-13 years in 59 schools in England and Wales. 29 schools (5372 students) were randomly assigned by stratified block randomisation to the control group to continue their usual smoking education and 30 (5358 students) to the intervention group. The intervention (ASSIST [A Stop Smoking In Schools Trial] programme) consisted of training influential students to act as peer supporters during informal interactions outside the classroom to encourage their peers not to smoke. Follow-up was immediately after the intervention and at 1 and 2 years. Primary outcomes were smoking in the past week in both the school year group and in a group at high risk of regular smoking uptake, which was identified at baseline as occasional, experimental, or ex-smokers. Analysis was by intention to treat. This study is registered, number ISRCTN55572965. FINDINGS: The odds ratio of being a smoker in intervention compared with control schools was 0.75 (95% CI 0.55-1.01) immediately after the intervention (n=9349 students), 0.77 (0.59-0.99) at 1-year follow-up (n=9147), and 0.85 (0.72-1.01) at 2-year follow-up (n=8756). The corresponding odds ratios for the high-risk group were 0.79 (0.55-1.13 [n=3561]), 0.75 (0.56-0.99 [n=3483]), and 0.85 (0.70-1.02 [n=3294]), respectively. In a three-tier multilevel model with data from all three follow-ups, the odds of being a smoker in intervention compared with control schools was 0.78 (0.64-0.96). INTERPRETATION: The results suggest that, if implemented on a population basis, the ASSIST intervention could lead to a reduction in adolescent smoking prevalence of public-health importance.

Ergodicity in natural earthquake fault networks.

Numerical simulations have shown that certain driven nonlinear systems can be characterized by mean-field statistical properties often associated with ergodic dynamics [C. D. Ferguson, W. Klein, and J. B. Rundle, Phys. Rev. E 60, 1359 (1999); D. Egolf, Science 287, 101 (2000)]. These driven mean-field threshold systems feature long-range interactions and can be treated as equilibriumlike systems with statistically stationary dynamics over long time intervals. Recently the equilibrium property of ergodicity was identified in an earthquake fault system, a natural driven threshold system, by means of the Thirumalai-Mountain (TM) fluctuation metric developed in the study of diffusive systems [K. F. Tiampo, J. B. Rundle, W. Klein, J. S. Sá Martins, and C. D. Ferguson, Phys. Rev. Lett. 91, 238501 (2003)]. We analyze the seismicity of three naturally occurring earthquake fault networks from a variety of tectonic settings in an attempt to investigate the range of applicability of effective ergodicity, using the TM metric and other related statistics. Results suggest that, once variations in the catalog data resulting from technical and network issues are accounted for, all of these natural earthquake systems display stationary periods of metastable equilibrium and effective ergodicity that are disrupted by large events. We conclude that a constant rate of events is an important prerequisite for these periods of punctuated ergodicity and that, while the level of temporal variability in the spatial statistics is the controlling factor in the ergodic behavior of seismic networks, no single statistic is sufficient to ensure quantification of ergodicity. Ergodicity in this application not only requires that the system be stationary for these networks at the applicable spatial and temporal scales, but also implies that they are in a state of metastable equilibrium, one in which the ensemble averages can be substituted for temporal averages in studying their spatiotemporal evolution.

Childhood eating and weight in eating disorders: a multi-centre European study of affected women and their unaffected sisters.

BACKGROUND: Previous studies have suggested that childhood eating and weight problems may be risk factors for eating disorders. Robust evidence is still lacking. AIMS: To investigate whether childhood eating and weight problems increase the risk of eating disorders in affected women compared to their unaffected sisters. METHODS: Women (150) with anorexia (AN) or bulimia nervosa (BN) recruited from clinical and community samples were compared to their unaffected sister closest in age on maternal reports of childhood eating and weight. RESULTS: Women with BN were significantly more overweight at the ages of 5 and 10 (both OR = 2.8, p < 0.01), ate a lot (OR = 1.3, p < 0.01), were less picky (OR = 0.6, p < 0.05) and ate quickly (OR = 2.3, p < 0.05) between the ages of 6 and 10 compared to their healthy sisters. Significantly more women with AN were described as having a higher weight at 6 months (OR = 0.8, p < 0.01) and 1 year (OR = 0.6, p < 0.01) compared to their healthy sisters. Childhood eating was comparable in the women with AN and their unaffected sisters. CONCLUSIONS: Traits of childhood overeating were more common in bulimic women compared to their unaffected siblings. Subjects with AN did not differ from their sisters on eating variables. The increased risk of BN due to childhood overweight suggests that prevention strategies for childhood obesity and overweight may therefore be applicable in BN.

Combined family trio and case-control analysis of the COMT Val158Met polymorphism in European patients with anorexia nervosa.

The high activity Val158 (H) allele of the dopamine-metabolizing enzyme catechol-O-methyltransferase (COMT) was associated with anorexia nervosa (AN) in a recent family trio-based study of patients from Israel. In an attempt to replicate this finding, we performed a combined family trio and case-control study in an European population from seven centers in six different countries (Austria, Germany, Great Britain, Italy [Milan], Italy [Florence], Slovenia, and Spain), together contributing a total of 372 family trios, 684 controls and 266 cases. TDT analyses of high (H) and low (L) alleles in family trios showed that H allele and L allele were each transmitted 101 times (chi(2) = 0, ns). Allele-wise case-control analysis using separate samples simply combined from the centers was also not significant, with the frequencies of the H allele 50% in cases and same in controls. Stratified analysis of data from all centers gave an odds ratio of 0.98 (Cornfield 95% confidence limits 0.78-1.24). Analysis by genotype was likewise not significant (overall chi(2) = 0.42). Because we were not able to support the primary hypothesis that Val158Met is a risk factor for AN, we did not perform secondary analysis of minimum body mass index (mBMI), age at onset or illness subtype (restricting or binge purging anorexia). Overall we found no support for the hypothesis that the Val158 allele of COMT gene is associated with AN in our combined European sample.

Grouping of coefficients for the calculation of inter-molecular similarity and dissimilarity using 2D fragment bit-strings.

This paper compares 22 different similarity coefficients when they are used for searching databases of 2D fragment bit-strings. Experiments with the National Cancer Institute s AIDS and IDAlert databases show that the coefficients fall into several well-marked clusters, in which the members of a cluster will produce comparable rankings of a set of molecules. These clusters provide a basis for selecting combinations of coefficients for use in data fusion experiments. The results of these experiments provide a simple way of increasing the effectiveness of fragment-based similarity searching systems.

Reducing risk for cardiovascular disease in uninsured women: combined results from two WISEWOMAN projects.

OBJECTIVE: to evaluate the effectiveness of a cardiovascular disease (CVD) risk factor reduction program for financially disadvantaged women. The program included cholesterol and blood pressure assessments and tailored physical activity and nutrition interventions. METHODS: Women who attended selected National Breast and Cervical Cancer Early Detection Program sites in North Carolina and Massachusetts received either enhanced physical activity and nutrition interventions (EI) or minimum interventions (MI). The effectiveness of EI was assessed by pooling data from the North Carolina and Massachusetts projects after 1 year, and a mixed models analysis of covariance was used to compare changes in CVD risk factors across groups. RESULTS: The blood pressure, total cholesterol, and high-density lipoprotein cholesterol profiles of both groups improved, body weight was maintained, and smoking declined. The 10-year estimated coronary heart disease death rate (per 1,000 women) at baseline was 64.8 for the El group and 61.9 for the MI group. The rate declined by 3.5 deaths per 1,000 for the EI and 0.7 per 1,000 for the MI. Although the decline was statistically significant for the EI group, the difference between groups was not significant. CONCLUSION: Further lifestyle intervention research targeting financially disadvantaged women is needed.

Cardiovascular disease risk factor intervention in low-income women: the North Carolina WISEWOMAN project.

OBJECTIVES: The North Carolina WISEWOMAN project was initiated to evaluate the feasibility of expanding an existing cancer screening program to include a cardiovascular disease (CVD) screening and intervention program among low-income women. METHODS: Seventeen North Carolina county health departments were designated as minimum intervention (MI), and 14 as enhanced intervention (EI). The EI included three specially constructed counseling sessions spanning 6 months using a structured assessment and intervention program tailored to lower income women. RESULTS: Of the 2,148 women screened, 40% had elevated total cholesterol (> or = 240 mg/dL), 39% had low high-density lipoprotein cholesterol (HDL-C) levels (< 45 mg/dL), and 63% were hypertensive (systolic blood pressure 140 and/or diastolic blood pressure > or = 90 mm Hg or on hypertensive medication). The majority of women (86%) had at least one of these three risk factors. Seventy-six percent were either overweight or obese. After 6 months of follow-up in the EI health departments, changes in total cholesterol levels, HDL-C levels, diastolic blood pressure, and BMI were observed (-5.8 mg/dL, -0.9 mg/dL, -1.7 mm Hg, and -0.3 kg/m(2), respectively), but were not significantly different from MI health departments. A dietary score that summarized fat and cholesterol intake improved by 2.1 units in the EI group, compared with essentially no change in the MI group. CONCLUSIONS: Expanding existing cancer screening programs to include CVD intervention was feasible and may be an effective means for promoting healthful dietary practices among low-income women.

Has the mammography quality standards act affected the mammography quality in North Carolina?

OBJECTIVE: The United States Food and Drug Administration implemented federal regulations governing mammography under the Mammography Quality Standards Act (MQSA) of 1992. During 1995, its first year in implementation, we examined the impact of the MQSA on the quality of mammography in North Carolina. MATERIALS AND METHODS: All mammography facilities were inspected during 1993-1994, and again in 1995. Both inspections evaluated mean glandular radiation dose, phantom image evaluation, darkroom fog, and developer temperature. Two mammography health specialists employed by the North Carolina Division of Radiation Protection performed all inspections and collected and codified data. RESULTS: The percentage of facilities that met quality standards increased from the first inspection to the second inspection. Phantom scores passing rate was 31.6% versus 78.2%; darkroom fog passing rate was 74.3% versus 88.5%; and temperature difference passing rate was 62.4% versus 86.9%. CONCLUSION: In 1995, the first year that the MQSA was in effect, there was a significant improvement in the quality of mammography in North Carolina. This improvement probably resulted from facilities' compliance with federal regulations.

Calcium-induced calcium release from intracellular stores is developmentally regulated in primary cultures of cerebellar granule neurons.

The properties of depolarization-evoked calcium transients are known to change during the maturation of dissociated cerebellar granule neuron cultures. Here, we assessed the role of the calcium-induced calcium release (CICR) mechanism in granule neuron maturation. Both depletion of intracellular calcium stores and the pharmacological blockade of CICR significantly reduced depolarization stimulated calcium transients in young but not older (>/=1 week) cultures. This functional decrease in the CICR signaling component was associated with the reduction of ryanodine receptor (RyR) immunoreactivity during granule neuron maturation both in culture and in the intact cerebellum. These observations are consistent with the idea that changes in RyR expression result in functional changes in calcium signaling transients during normal neuronal development in the intact mammalian cerebellum as well as in reduced neuronal cultures. Pharmacological disruption of CICR during neuron differentiation in vitro resulted in dose-dependent changes in survival, GAP-43 expression, and the acquisition of the glutamatergic neurotransmitter phenotype. Together, these results indicate that CICR function plays a physiologically relevant role in regulating early granule neuron differentiation in vitro and is likely to play a role in cerebellar maturation.

Effectiveness of retrieval in similarity searches of chemical databases: a review of performance measures.

This article reviews measures for evaluating the effectiveness of similarity searches in chemical databases, drawing principally upon the many measures that have been described previously for evaluating the performance of text search engines. The use of the various measures is exemplified by fragment-based 2D similarity searches on several databases for which both structural and bioactivity data are available. It is concluded that the cumulative recall and G-H score measures are the most useful of those tested.