Demographic and attitudinal antecedents of consumers' use and self-investment trajectories over time in an online TV content platform

Purpose: To investigate if online TV content platforms create value for consumers (and increase use) by offering its users the possibility to self-invest in the service (by giving personal content preferences). We link demographic and attitudinal antecedents to the relation between self-investment and use. Design/methodology/approach: Data were collected together with a Belgian media company (N = 4,136). To test the effects a latent growth model was composed in a multigroup setting with gender as the grouping variable. The model is analyzed through structural equation modeling in Mplus 8.0. Findings: In general, strong relations between self-investment and increased use were found, although the effect of self-investment on use was stronger for female consumers. Furthermore, we established strong hedonic effects on using and investing in the service. For men, easy to use platforms lead to less self-investment. Research limitations/implications: Our findings are restricted to free services. Furthermore, attitudinal variables are antecedents of behaviors. However, a more complex interplay between behavioral and attitudinal variables is possible. Further research could use repeatedly measured attitudinal measures and link these to behaviors over time. Practical implications: Service developers could offer different platform interactions to different segments to create consumer value. Women seem more receptive for extra functionalities, such as the possibility to indicate preferences. Men mainly focus on the content offered. Originality/value: This study focuses on a new form of media distribution, online TV content platforms, where we investigate two related behaviors of users over time (self-investment and use) instead of a general approximation of use. Multi-source data were used

The land management tool: Developing a climate service in Southwest UK

Seasonal climate forecasts (SCFs) have significant potential to support shorter-term agricultural decisions and longer-term climate adaptation plans, but uptake in Europe has to date been low. Under the European Union funded project, European Provision Of Regional Impacts Assessments on Seasonal and Decadal Timescales (EUPORIAS) we have developed the Land Management Tool (LMTool), a prototype seasonal climate service for land managers, working closely in collaboration with two stakeholder organizations, Clinton Devon Estates (CDE) and the National Farmers Union (NFU). LMTool was one of several prototype climate services selected for development within EUPORIAS, including those for the UK transport network, food security in Ethiopia, renewable energy production, hydroelectric energy production in Sweden, and river management in two French basins. The LMTool provides SCFs (1–3 months ahead) to farmers in the Southwest UK, alongside 14-day site specific weather forecasts during the winter months when the skill of seasonal forecasts is greatest. We describe the processes through which the LMTool was co-designed and developed with the farmers, its technical development and key features; critically examine the lessons learned and their implications for providing future climate services for land managers; and finally assess the feasibility of delivering an operational winter seasonal climate service for UK land managers. A number of key learning points from developing the prototype may benefit future work in climate services for the land management and agriculture sector; many of these points are also valid for climate services in other sectors. Prototype development strongly benefitted from; working with intermediaries to identify representative, engaged land managers; an iterative and flexible process of co-design with the farmer group; and from an interdisciplinary project team. Further work is needed to develop a better understanding of the role of forecast skill in land management decision making, the potential benefits of downscaling and how seasonal forecasts can help support land managers decision-making processes. The prototype would require considerable work to implement a robust operational forecast system, and a longer period to demonstrate the value of the services provided. Finally, the potential for such services to be applied more widely in Europe is not well understood and would require further stakeholder engagement and forecast development

Stable X chromosome reactivation in female human induced pluripotent stem cells

In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs) leads to reactivation of the inactive X chromosome (Xi), we have generated iPSC lines from fibroblasts heterozygous for large X-chromosomal deletions. These fibroblasts show completely skewed XCI of the mutated X chromosome, enabling monitoring of X chromosome reactivation (XCR) and XCI using allele-specific single-cell expression analysis. This approach revealed that XCR is robust under standard culture conditions, but does not prevent reinitiation of XCI, resulting in a mixed population of cells with either two active X chromosomes (Xas) or one Xa and one Xi. This mixed population of XaXa and XaXi cells is stabilized in naive human stem cell medium, allowing expansion of clones with two Xas

Heterozygosity for bisphosphoglycerate mutase deficiency expressing clinically as congenital erythrocytosis: A case series and literature review

Erythrocytosis is associated with increased red blood cell mass and can be either congenital or acquired. Congenital secondary causes are rare and include germline variants increasing haemoglobin (Hb)-oxygen affinity (e.g., Hb or bisphosphoglycerate mutase (BPGM) variants) or affecting oxygen-sensing pathway proteins. Here, we describe five adults from three kindreds with erythrocytosis associated with heterozygosity for BPGM variants, including one novel. Functional analyses showed partial BPGM deficiency, reduced 2,3-bisphosphoglycerate levels and/or increased Hb-oxygen affinity. We also review currently known BPGM variants. This study contributes to raising awareness of BPGM variants, and in particular that heterozygosity for BPGM deficiency may already manifest clinically

Epigenome-wide association study of plasma lipids in West Africans: the RODAM study

BACKGROUND: DNA-methylation has been associated with plasma lipid concentration in populations of diverse ethnic backgrounds, but epigenome-wide association studies (EWAS) in West-Africans are lacking. The aim of this study was to identify DNA-methylation loci associated with plasma lipids in Ghanaians. METHODS: We conducted an EWAS using Illumina 450k DNA-methylation array profiles of extracted DNA from 663 Ghanaian participants. Differentially methylated positions (DMPs) were examined for association with plasma total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, and triglycerides concentrations using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, and technical covariates. Findings were replicated in independent cohorts of different ethnicities. FINDINGS: We identified one significantly associated DMP with triglycerides (cg19693031 annotated to TXNIP, regression coefficient beta -0.26, false discovery rate adjusted p-value 0.001), which replicated in-silico in South African Batswana, African American, and European populations. From the top five DMPs with the lowest nominal p-values, two additional DMPs for triglycerides (CPT1A, ABCG1), two DMPs for LDL-cholesterol (EPSTI1, cg13781819), and one for TC (TXNIP) replicated. With the exception of EPSTI1, these loci are involved in lipid transport/metabolism or are known GWAS-associated loci. The top 5 DMPs per lipid trait explained 9.5% in the variance of TC, 8.3% in LDL-cholesterol, 6.1% in HDL-cholesterol, and 11.0% in triglycerides. INTERPRETATION: The top DMPs identified in this study are in loci that play a role in lipid metabolism across populations, including West-Africans. Future studies including larger sample size, longitudinal study design and translational research is needed to increase our understanding on the epigenetic regulation of lipid metabolism among West-African populations. FUNDING: European Commission under the Framework Programme (grant number: 278901)

Polyethylene thickness is a risk factor for wear necessitating insert exchange

PURPOSE: The aim of this observational study was to investigate the optimal minimal polyethylene (PE) thickness in total knee arthroplasty (TKA) and identify other risk factors associated with revision of the insert due to wear. METHODS: A total of 84 TKA were followed for 11-16 years. All patients received the same prosthesis design (Interax; Howmedica/ Stryker) with halfbearings: separate PE-inserts medially and laterally. Statistical analysis comprised Cox-regression to correct for confounding. RESULTS: Eight knees (9.5%) had been revised due to thinning inserts and an additional patient is scheduled for revision. PE thickness, diagnosis, BMI and weight are risk factors for insert exchange. For each millimetre decrease in PE thickness, the risk of insert exchange increases 3.0 times, which remains after correction for age, gender, weight, diagnosis and femoral-tibial angle. Insert exchange was 4.73 times more likely in OA-patients compared to RA-patients. For every unit increase in BMI and weight the risk for insert exchange increases 1.40 times and 1.14 times, respectively. CONCLUSIONS: In conclusion we therefore advise against the use of thin PE inserts in modular TKA and recommend PE inserts with a minimal 8-mm thickness.Optimising joint reconstruction management in arthritis and bone tumour patient

Evidence for Significant Overlap between Common Risk Variants for Crohn's Disease and Ankylosing Spondylitis

BACKGROUND: A multicenter genome-wide association scan for Crohn's Disease (CD) has recently reported 40 CD susceptibility loci, including 29 novel ones (19 significant and 10 putative). To gain insight into the genetic overlap between CD and ankylosing spondylitis (AS), these markers were tested for association in AS patients. PRINCIPAL FINDINGS: Two previously established associations, namely with the MHC and IL23R loci, were confirmed. In addition, rs2872507, which maps to a locus associated with asthma and influences the expression of the ORMDL3 gene in lymphoblastoid cells, showed a significant association with AS (p = 0.03). In gut biopsies of AS and CD patients, ORMDL3 expression was not significantly different from controls and no correlation was found with the rs2872507 genotype (Spearman's rho: -0.067). The distribution of p-values for the remaining 36 SNPs was significantly skewed towards low p-values unless the top 5 ranked SNPs (ORMDL3, NKX2-3, PTPN2, ICOSLG and MST1) were excluded from the analysis. CONCLUSIONS: Association analysis using risk variants for CD led to the identification of a new risk variant associated with AS (ORMDL3), underscoring a role for ER stress in AS. In addition, two known and five potentially relevant associations were detected, contributing to common susceptibility of CD and AS

Epigenetics and developmental programming of welfare and production traits in farm animals

The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the ‘developmental origins of health and disease’ or ‘DOHaD’ hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems