Comparison of the HUI3 with the SF-36 Preference Based SF-6D in a Clinical Trial Setting

AbstractObjectiveTo test the hypothesis that the Health Utilities Index Mark III (HUI3) and the SF-6D, based on the SF-36, generate similar health state values, and to test and compare their discriminant validity and responsiveness.MethodsThe HUI3 and SF-36 were administered to 331 patients enrolled in a double-blind, multinational phase III clinical trial in patients undergoing percutaneous coronary intervention before hospital discharge and 6 months thereafter.ResultsThe mean SF-6D baseline health state score was 0.67 compared to the HUI3 of 0.63 with r of 0.616 and intraclass correlation coefficient of 0.40. The relationship was nonlinear with greatest divergence found at the lower levels of health. Both measures were found to agree with known differences in health and to be responsive to changes over time. Nevertheless, disagreement resulted in different estimates of change from baseline (0.08 vs. 0.154).ConclusionBoth measures deployed in the present study were found to have discriminant validity, and to be responsive to changes over time in coronary artery disease conditions. Nevertheless, the measures generated different estimates of health state values for this patient population. These differences might in part be the consequence of the health status descriptive system for the HUI that may have been more in line with the hospitalized state than that for the SF-6D. These findings seemed to indicate that measures deployed are not interchangeable for use in cost-utility analysis. More head-to-head comparisons between these two measures are needed to further define and compare relationships in different patient populations

Human Resources and the Resource Based View of the Firm

The resource-based view (RBV) of the firm has influenced the field of strategic human resource management (SHRM) in a number of ways. This paper explores the impact of the RBV on the theoretical and empirical development of SHRM. It explores how the fields of strategy and SHRM are beginning to converge around a number of issues, and proposes a number of implications of this convergence

Smoking, self-regulation and moral positioning: a focus group study with British smokers from a disadvantaged community

Smoking in many Western societies has become a both moral aand health issue in recent years, but little is known about how smokers position themselves and regulate their behaviour in this context. In this article, we report the findings from a study investigating how smokers from an economically disadvantaged community in the East Midlands (UK) respond to concerns about the health impact of smoking on others. We conducted ten focus group (FG) discussions with mixed groups (by smoking status and gender; N = 58 participants) covering a range of topics, including smoking norms, self-regulation, and smoking in diverse contexts. We transcribed all FG discussions before analysing the data using techniques from discourse anlysis. Smokers in general positioned themselves as socially responsible smokers and morally upstanding citizens. This position was bolstered in two main ways: ‘everyday accommodation', whereby everyday efforts to accommodate the needs of non-smokers were referenced, and ‘taking a stand', whereby proactive interventions to prevent smoking in (young) others were cited. We suggest that smoking cessation campaigns could usefully be informed by this ethic of care for others

Distinguishing Family from Friends

Kinship and friendship are key human relationships. Increasingly, data suggest that people are not less altruistic toward friends than close kin. Some accounts suggest that psychologically we do not distinguish between them; countering this is evidence that kinship provides a unique explanatory factor. Using the Implicit Association Test, we examined how people implicitly think about close friends versus close kin in three contexts. In Experiment 1, we examined generic attitudinal dispositions toward friends and family. In Experiment 2, attitude similarity as a marker of family and friends was examined, and in Experiments 3 and 4, strength of in-group membership for family and friends was examined. Findings show that differences exist in implicit cognitive associations toward family and friends. There is some evidence that people hold more positive general dispositions toward friends, associate attitude similarity more with friends, consider family as more representative of the in-group than friends, but see friends as more in-group than distant kin

Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi

Depression affects 10-15% of pregnant women and has been associated with preterm delivery and later developmental, behavioural and learning disabilities. We tested the hypothesis that maternal depression is associated with DNA methylation alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes isolated from 38 antepartum maternal and 44 neonatal cord blood samples were analyzed using Illumina Methylation 450 K microarrays. Previously obtained methylation data sets using methylated DNA immunoprecipitation and array-hybridization of 62 postmortem hippocampal samples of adult males were re-analyzed to test associations with history of maternal depression. We found 145 (false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially methylated CG-sites in cord blood T lymphocytes of neonates from the maternal depression group as compared with the control group. However, no significant DNA methylation differences were detected in the antepartum maternal T lymphocytes of our preliminary data set. We also detected 294 differentially methylated probes (FDR q<0.1) in hippocampal samples associated with history of maternal depression. We observed a significant overlap (P=0.002) of 33 genes with changes in DNA methylation in T lymphocytes of neonates and brains of adult offspring. Many of these genes are involved in immune system functions. Our results show that DNA methylation changes in offspring associated with maternal depression are detectable at birth in the immune system and persist to adulthood in the brain. This is consistent with the hypothesis that system-wide epigenetic changes are involved in life-long responses to maternal depression in the offspring. © 2015 Translational Psychiatry

Activation of NK Cells by an Endocytosed Receptor for Soluble HLA-G

Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct from those generated at the plasma membrane. The activity of natural killer (NK) cells, which are important effectors of innate immunity and regulators of adaptive immunity, is controlled primarily by receptors that are at the cell surface. Here we show that cytokine secretion by resting human NK cells is induced by soluble, but not solid-phase, antibodies to the killer cell immunoglobulin-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen (HLA)-G. KIR2DL4 was constitutively internalized into Rab5-positive compartments via a dynamin-dependent process. Soluble HLA-G was endocytosed into KIR2DL4–containing compartments in NK cells and in 293T cells transfected with KIR2DL4. Chemokine secretion induced by KIR2DL4 transfection into 293T cells occurred only with recombinant forms of KIR2DL4 that trafficked to endosomes. The profile of genes up-regulated by KIR2DL4 engagement on resting NK cells revealed a proinflammatory/proangiogenic response. Soluble HLA-G induced secretion of a similar set of cytokines and chemokines. This unique stimulation of resting NK cells by soluble HLA-G, which is endocytosed by KIR2DL4, implies that NK cells may provide useful functions at sites of HLA-G expression, such as promotion of vascularization in maternal decidua during early pregnancy

Intracellular SERS nanoprobes for distinction of different neuronal cell types.

Distinction between closely related and morphologically similar cells is difficult by conventional methods especially without labeling. Using nuclear-targeted gold nanoparticles (AuNPs) as intracellular probes we demonstrate the ability to distinguish between progenitor and differentiated cell types in a human neuroblastoma cell line using surface-enhanced Raman spectroscopy (SERS). SERS spectra from the whole cell area as well as only the nucleus were analyzed using principal component analysis that allowed unambiguous distinction of the different cell types. SERS spectra from the nuclear region showed the developments during cellular differentiation by identifying an increase in DNA/RNA ratio and proteins transcribed. Our approach using nuclear-targeted AuNPs and SERS imaging provides label-free and noninvasive characterization that can play a vital role in identifying cell types in biomedical stem cell research

Whole genome sequence analysis of the TALLYHO/Jng mouse

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes. Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing runs. Genome-wide, we found approximately 4.31 million homozygous single nucleotide polymorphisms (SNPs) and 1.10 million homozygous small insertions and deletions (indels) of which 98,899 SNPs and 163,720 indels were unique to the TH strain compared to 28 previously sequenced inbred mouse strains. In order to identify potentially clinically-relevant genes, we intersected our list of SNP and indel variants with human orthologous genes in which variants were associated in GWAS studies with obesity, diabetes, and metabolic syndrome, and with genes previously shown to confer a monogenic obesity phenotype in humans, and found several candidate variants that could be functionally tested using TH mice. Further, we filtered our list of variants to those occurring in an obesity quantitative trait locus, tabw2, identified in TH mice and found a missense polymorphism in the Cidec gene and characterized this variant’s effect on protein function. Conclusions: We generated a complete catalog of variants in TH mice using the data from whole genome sequencing. Our findings will facilitate the identification of causal variants that underlie metabolic diseases in TH mice and will enable identification of candidate susceptibility genes for complex human obesity and type 2 diabetes