Whole-genome SNP association analysis of reproduction traits in the Finnish Landrace pig breed

<p>Abstract</p> <p>Background</p> <p>Good genetic progress for pig reproduction traits has been achieved using a quantitative genetics-based multi-trait BLUP evaluation system. At present, whole-genome single nucleotide polymorphisms (SNP) panels provide a new tool for pig selection. The purpose of this study was to identify SNP associated with reproduction traits in the Finnish Landrace pig breed using the Illumina PorcineSNP60 BeadChip.</p> <p>Methods</p> <p>Association of each SNP with different traits was tested with a weighted linear model, using SNP genotype as a covariate and animal as a random variable. Deregressed estimated breeding values of the progeny tested boars were used as the dependent variable and weights were based on their reliabilities. Statistical significance of the associations was based on Bonferroni-corrected <it>P</it>-values.</p> <p>Results</p> <p>Deregressed estimated breeding values were available for 328 genotyped boars. Of the 62 163 SNP in the chip, 57 868 SNP had a call rate > 0.9 and 7 632 SNP were monomorphic. Statistically significant results (<it>P</it>-value < 2.0E-06) were obtained for total number of piglets born in first and later parities and piglet mortality between birth and weaning in later parity, and suggestive associations (<it>P</it>-value < 4.0E-06) for piglet mortality between birth and weaning in first parity, number of stillborn piglets in later parity, first farrowing interval and second farrowing interval. Two of the statistically significant regions for total number of piglets born in first and later parities are located on chromosome 9 around 95 and 79 Mb. The estimated SNP effect in these regions was approximately one piglet between the two homozygote classes. By combining the two most significant SNP in these regions, favourable double homozygote animals are expected to have 1.3 piglets (<it>P</it>-value = 1.69E-08) more than unfavourable double homozygote animals. A region on chromosome 9 (66 Mb) was statistically significant for piglet mortality between birth and weaning in later parity (0.44 piglets between homozygotes, <it>P</it>-value = 6.94E-08).</p> <p>Conclusions</p> <p>Three separate regions on chromosome 9 gave significant results for litter size and pig mortality. The frequencies of favourable alleles of the significant SNP are moderate in the Finnish Landrace population and these SNP are thus valuable candidates for possible marker-assisted selection.</p

Study protocol: Evaluating the impact of a rural Australian primary health care service on rural health

BACKGROUND: Rural communities throughout Australia are experiencing demographic ageing, increasing burden of chronic diseases, and de-population. Many are struggling to maintain viable health care services due to lack of infrastructure and workforce shortages. Hence, they face significant health disadvantages compared with urban regions. Primary health care yields the best health outcomes in situations characterised by limited resources. However, few rigorous longitudinal evaluations have been conducted to systematise them; assess their transferability; or assess sustainability amidst dynamic health policy environments. This paper describes the study protocol of a comprehensive longitudinal evaluation of a successful primary health care service in a small rural Australian community to assess its performance, sustainability, and responsiveness to changing community needs and health system requirements. METHODS/DESIGN: The evaluation framework aims to examine the health service over a six-year period in terms of: (a) Structural domains (health service performance; sustainability; and quality of care); (b) Process domains (health service utilisation and satisfaction); and (c) Outcome domains (health behaviours, health outcomes and community viability). Significant international research guided the development of unambiguous reliable indicators for each domain that can be routinely and unobtrusively collected. Data are to be collected and analysed for trends from a range of sources: audits, community surveys, interviews and focus group discussions. DISCUSSION: This iterative evaluation framework and methodology aims to ensure the ongoing monitoring of service activity and health outcomes that allows researchers, providers and administrators to assess the extent to which health service objectives are met; the factors that helped or hindered achievements; what worked or did not work well and why; what aspects of the service could be improved and how; what benefits have been realised and for whom; the level of community satisfaction with the service; and the impact of a health service on community viability. While the need to reduce the rural-urban health service disparity in Australia is pressing, the evidence regarding how to move forward is inadequate. This comprehensive evaluation will add significant new knowledge regarding the characteristics associated with a sustainable rural primary health care service

Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial

Background Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. Methods/design A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. Discussion The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. Trial registration Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015

Exploring the role of external experts in supporting staff to implement psychosocial interventions in care home settings: results from the process evaluation of a randomized controlled trial

Background: Psychosocial interventions offer opportunities to improve care for people with dementia in care homes. However, implementation is often led by staff who are not well prepared for the role. Some interventions use external experts to support staff. However little is known about external expert, care home staff and manager perceptions of such support. This paper addresses this gap. Methods: Multi-methods study within a process evaluation of a cluster randomised controlled trial of Dementia Care MappingTM (DCM). Interviews were conducted with six external experts who also completed questionnaires, 17 care home managers and 25 care home staff responsible for DCM implementation. Data were analysed using descriptive statistics and template analysis. Results: Three themes were identified: the need for expert support, practicalities of support and broader impacts of providing support. Expert support was vital for successful DCM implementation, although the five-days provided was felt to be insufficient. Some homes felt the support was inflexible and did not consider their individual needs. Practical challenges of experts being located at a geographical distance from the care homes, limited when and how support was available. Experts gained knowledge they were able to then apply in delivering DCM training. Experts were not able to accurately predict which homes would be able to implement DCM independently in future cycles. Conclusions: An external expert may form a key component of successful implementation of psychosocial interventions in care home settings. Future research should explore optimal use of the expert role

Sex-specific Trans-regulatory Variation on the Drosophila melanogaster X Chromosome

The X chromosome constitutes a unique genomic environment because it is present in one copy in males, but two copies in females. This simple fact has motivated several theoretical predictions with respect to how standing genetic variation on the X chromosome should differ from the autosomes. Unmasked expression of deleterious mutations in males and a lower census size are expected to reduce variation, while allelic variants with sexually antagonistic effects, and potentially those with a sex-specific effect, could accumulate on the X chromosome and contribute to increased genetic variation. In addition, incomplete dosage compensation of the X chromosome could potentially dampen the male-specific effects of random mutations, and promote the accumulation of X-linked alleles with sexually dimorphic phenotypic effects. Here we test both the amount and the type of genetic variation on the X chromosome within a population of Drosophila melanogaster, by comparing the proportion of X linked and autosomal trans-regulatory SNPs with a sexually concordant and discordant effect on gene expression. We find that the X chromosome is depleted for SNPs with a sexually concordant effect, but hosts comparatively more SNPs with a sexually discordant effect. Interestingly, the contrasting results for SNPs with sexually concordant and discordant effects are driven by SNPs with a larger influence on expression in females than expression in males. Furthermore, the distribution of these SNPs is shifted towards regions where dosage compensation is predicted to be less complete. These results suggest that intrinsic properties of dosage compensation influence either the accumulation of different types of trans-factors and/or their propensity to accumulate mutations. Our findings document a potential mechanistic basis for sex-specific genetic variation, and identify the X as a reservoir for sexually dimorphic phenotypic variation. These results have general implications for X chromosome evolution, as well as the genetic basis of sex-specific evolutionary change

C5a Enhances Dysregulated Inflammatory and Angiogenic Responses to Malaria In Vitro: Potential Implications for Placental Malaria

Placental malaria (PM) is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs) and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI) enhanced C5a receptor expression (CD88) on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10), chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta) and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function

The Economics of Dementia-Care Mapping in Nursing Homes:A Cluster-Randomised Controlled Trial

Background: Dementia-care mapping (DCM) is a cyclic intervention aiming at reducing neuropsychiatric symptoms in people with dementia in nursing homes. Alongside an 18-month cluster-randomized controlled trial in which we studied the effectiveness of DCM on residents and staff outcomes, we investigated differences in costs of care between DCM and usual care in nursing homes. Methods: Dementia special care units were randomly assigned to DCM or usual care. Nurses from the intervention care homes received DCM training, a DCM organizational briefing day and conducted the 4-months DCM-intervention twice during the study. A single DCM cycle consists of observation, feedback to the staff, and action plans for the residents. We measured costs related to health care consumption, falls and psychotropic drug use at the resident level and absenteeism at the staff level. Data were extracted from resident files and the nursing home records. Prizes were determined using the Dutch manual of health care cost and the cost prices delivered by a pharmacy and a nursing home. Total costs were evaluated by means of linear mixed-effect models for longitudinal data, with the unit as a random effect to correct for dependencies within units. Results: 34 units from 11 nursing homes, including 318 residents and 376 nursing staff members participated in the cost analyses. Analyses showed no difference in total costs. However certain changes within costs could be noticed. The intervention group showed lower costs associated with outpatient hospital appointments over time (p = 0.05) than the control group. In both groups, the number of falls, costs associated with the elderly-care physician and nurse practitioner increased equally during the study (p Conclusions: DCM is a cost-neutral intervention. It effectively reduces outpatient hospital appointments compared to usual care. Other considerations than costs, such as nursing homes' preferences, may determine whether they adopt the DCM method

Population genetics of sexual conflict in the genomic era

Sexual conflict occurs when selection acts in opposing directions on males and females. Case studies in both vertebrates and invertebrates indicate that sexual conflict maintains genetic diversity through balancing selection, which might explain why many populations show more genetic variation than expected. Recent population genomic approaches based on different measures of balancing selection have suggested that sexual conflict can arise over survival, not just reproductive fitness as previously thought. A fuller understanding of sexual conflict will provide insight into its contribution to adaptive evolution and will reveal the constraints it might impose on populations