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Within the temporal psychology literature, evidence has been presented for a relationship between a variety of health indicators, including alcohol-related problems, as well as symptoms of anxiety and depression, and a variety of temporal constructs. Recently, it was claimed that the two factors of the Consideration of Future Consequences (CFC) Scale-14 (CFCS-14) were both practically and conceptually useful in understanding the relationship between CFC and various criterion variables. The present study examined the relationship between these two factors (consideration of immediate and consideration of future consequences) and symptoms of anxiety and depression, as well as problematic alcohol use. Participants were recruited from a University in the North West of England, and completed the CFCS-14, the Alcohol Use Disorders Identification Test, and the Hospital Anxiety and Depression Scale. Results offer support for the psychometric validity and internal consistency of the CFCS-14, and further reveal a modest relationship between its factors and criterion variables. Compared to temporal psychology measures focussing on time attitudes or time perspective, the clinical or practical utility of the CFCS-14 in understanding these health domains may be limited., Author(s): Andrew Percy [sup.1], Michael T. McKay [sup.2], John L. Perry [sup.3], Jon C. Cole [sup.2] Author Affiliations: (1) grid.4777.3, 0000 0004 0374 7521, School of Social Sciences, Education, & [...]

Two papers in this issue, by Bruns et al. and Zhao et al., show that megakaryocytes constitute a niche for hematopoietic stem cells in the mouse bone marrow and produce factors that regulate hematopoietic stem cell quiescence and proliferation. Multiple bone marrow stromal cell types have been identified as hematopoietic stem cell (HSC)-regulating niche cells.sup.1,2,3,4,5,6,7. However, whether HSC progeny can serve directly as HSC niche cells has not previously been shown. Here we report a dichotomous role of megakaryocytes (MKs) in both maintaining HSC quiescence during homeostasis and promoting HSC regeneration after chemotherapeutic stress. We show that MKs are physically associated with HSCs in the bone marrow of mice and that MK ablation led to activation of quiescent HSCs and increased HSC proliferation. RNA sequencing (RNA-seq) analysis revealed that transforming growth factor [beta]1 (encoded by Tgfb1) is expressed at higher levels in MKs as compared to other stromal niche cells. MK ablation led to reduced levels of biologically active TGF-[beta]1 protein in the bone marrow and nuclear-localized phosphorylated SMAD2/3 (pSMAD2/3) in HSCs, suggesting that MKs maintain HSC quiescence through TGF-[beta]-SMAD signaling.sup.8,9. Indeed, TGF-[beta]1 injection into mice in which MKs had been ablated restored HSC quiescence, and conditional deletion of Tgfb1 in MKs increased HSC activation and proliferation. These data demonstrate that TGF-[beta]1 is a dominant signal emanating from MKs that maintains HSC quiescence. However, under conditions of chemotherapeutic challenge, MK ablation resulted in a severe defect in HSC expansion. In response to stress, fibroblast growth factor 1 (FGF1) signaling from MKs transiently dominates over TGF-[beta] inhibitory signaling to stimulate HSC expansion.sup.10,11. Overall, these observations demonstrate that MKs serve as HSC-derived niche cells to dynamically regulate HSC function., Author(s): Meng Zhao [sup.1] , John M Perry [sup.1] , Heather Marshall [sup.1] , Aparna Venkatraman [sup.1] [sup.2] , Pengxu Qian [sup.1] , Xi C He [sup.1] , Jasimuddin Ahamed [...]

Multiple bone marrow stromal cell types have been identified as hematopoietic stem cell (HSC)-regulating niche cells (1-7). However, whether HSC progeny can serve directly as HSC niche cells has not previously been shown. Here we report a dichotomous role of megakaryocytes (MKs) in both maintaining HSC quiescence during homeostasis and promoting HSC regeneration after chemotherapeutic stress. We show that MKs are physically associated with HSCs in the bone marrow of mice and that MK ablation led to activation of quiescent HSCs and increased HSC proliferation. RNA sequencing (RNA-seq) analysis revealed that transforming growth factor β1 (encoded by Tgfb1) is expressed at higher levels in MKs as compared to other stromal niche cells. MK ablation led to reduced levels of biologically active TGF-β1 protein in the bone marrow and nuclear-localized phosphorylated SMAD2/3 (pSMAD2/3) in HSCs, suggesting that MKs maintain HSC quiescence through TGF-β-SMAD signaling (89). Indeed, TGF-β1 injection into mice in which MKs had been ablated restored HSC quiescence, and conditional deletion of Tgfb1 in MKs increased HSC activation and proliferation. These data demonstrate that TGF-β1 is a dominant signal emanating from MKs that maintains HSC quiescence. However, under conditions of chemotherapeutic challenge, MK ablation resulted in a severe defect in HSC expansion. In response to stress, fibroblast growth factor 1 (FGF1) signaling from MKs transiently dominates over TGF-β inhibitory signaling to stimulate HSC expansion (10,11). Overall, these observations demonstrate that MKs serve as HSC-derived niche cells to dynamically regulate HSC function., Although feedback from differentiated hematopoietic cells has been proposed as a mechanism to influence HSCs (12), genetic evidence for a role of HSC progeny cells in serving directly as HSC [...]

Robert Mayer White, the first administrator of NOAA, passed away on October 15, 2015. In his long and diverse career, he provided visionary leadership in the National Weather Service, the [...]

Maternal genomic imprinting is crucial for the maintenance of adult stem cells, which is accomplished by maintaining long-term haematopoietic stem cell quiescence. Epigenetic control of adult stem cells A new study by Linheng Li and colleagues investigates the effect of deletion of the H19 differentially methylated region (H19-DMR) in haematopoietic stem cells. The DMR is known to control expression of the imprinted H19 and Igf2 genes from the H19-Igf2 locus, restricting H19 expression to the maternal allele and Igf2 to the paternal allele. The authors report the predominant expression of a list of maternally expressed growth-restricting imprinted genes in long-term haematopoietic stem cells (LT-HSCs), but not in proliferating short-term HSCs, suggesting a crucial role for genomic imprinting in maintaining quiescent LT-HSCs. The epigenetic regulation of imprinted genes by monoallelic DNA methylation of either maternal or paternal alleles is critical for embryonic growth and development.sup.1. Imprinted genes were recently shown to be expressed in mammalian adult stem cells to support self-renewal of neural and lung stem cells.sup.2,3,4; however, a role for imprinting per se in adult stem cells remains elusive. Here we show upregulation of growth-restricting imprinted genes, including in the H19-Igf2 locus.sup.5, in long-term haematopoietic stem cells and their downregulation upon haematopoietic stem cell activation and proliferation. A differentially methylated region upstream of H19 (H19-DMR), serving as the imprinting control region, determines the reciprocal expression of H19 from the maternal allele and Igf2 from the paternal allele.sup.1. In addition, H19 serves as a source of miR-675, which restricts Igf1r expression.sup.6. We demonstrate that conditional deletion of the maternal but not the paternal H19-DMR reduces adult haematopoietic stem cell quiescence, a state required for long-term maintenance of haematopoietic stem cells, and compromises haematopoietic stem cell function. Maternal-specific H19-DMR deletion results in activation of the Igf2-Igfr1 pathway, as shown by the translocation of phosphorylated FoxO3 (an inactive form) from nucleus to cytoplasm and the release of FoxO3-mediated cell cycle arrest, thus leading to increased activation, proliferation and eventual exhaustion of haematopoietic stem cells. Mechanistically, maternal-specific H19-DMR deletion leads to Igf2 upregulation and increased translation of Igf1r, which is normally suppressed by H19-derived miR-675. Similarly, genetic inactivation of Igf1r partly rescues the H19-DMR deletion phenotype. Our work establishes a new role for this unique form of epigenetic control at the H19-Igf2 locus in maintaining adult stem cells., Author(s): Aparna Venkatraman [sup.1] [sup.2] , Xi C. He [sup.1] , Joanne L. Thorvaldsen [sup.3] , Ryohichi Sugimura [sup.1] , John M. Perry [sup.1] , Fang Tao [sup.1] , Meng [...]

Effectuation represents a paradigmatic shift in the way that we understand entrepreneurship. Since its introduction, however, few researchers have attempted to empirically test effectuation. Our purpose is to encourage effectuation [...]

This paper uses national data on individual physicians and two control groups to provide evidence on the extent to which each of five medical malpractice reforms impacts the decision to [...]

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1467-9795.2009.00418.x Byline: John Perry (1) Keywords: analogy; moral reasoning; homosexuality; gentiles; early church; Acts 10-15; Jerusalem Council; Anglican Communion; Episcopal Church; Windsor Report Abstract: ABSTRACT This paper examines the argument that moral approval of homosexuality is analogous to the early church's inclusion of gentiles. The analogy has a long but often overlooked history, dating back to the start of the modern gay-rights movement. It has recently gained greater prominence because of its importance to the Episcopal Church's debate with the wider Anglican Communion. Beginning with the Episcopal Church argument, we see that there are five specific areas most in need of further clarification. In this essay I examine significant uses of the analogy from the prior 25 years to see how effectively they address these five areas. I conclude that the conversation surrounding the Gentile Analogy is the current, best hope for mutual understanding among Christians about homosexuality. However, if the analogy is to advance the Christian conversation, much greater care and precision is needed in its application from traditionalists and revisionists alike. Author Affiliation: (1)Christ ChurchUniversity of OxfordSt. AldatesOxford OX1 1DP44.1865.286.855john.perry@chch.ox.ac.uk

There has been a dramatic increase in the authority granted to nurse practitioners (NP) and physician assistants (PA). This 'expanded' authority has changed who can provide health-care services and has weakened the control physicians have traditionally held over the provision of medical services. These changes in regulation have varied by occupation, state, and year and provide variation that can be exploited to empirically measure the individual and collective impacts of changes in NP authority and PA authority on practitioner incomes. It is found that changes in NP and PA regulatory authority do impact the labor markets of all three practitioner categories. NPs having greater practice authority brings physician incomes down, has differential impacts on PA incomes, and improves their own earnings, other factors held constant. PAs having increased authority has a downward effect on NP earnings, a positive impact on physician income, and little impact on their own incomes. (JEL I18, J18, J44, H75), I. INTRODUCTION A. Motivation Health care is a large, dynamic, and growing segment of the economy. Of its many interesting facets is the fact that its occupations are nearly universally [...]

The United Kingdom Labour party's focus on council homes is seen as an opportunity for reforms in the housing finance system. The government expects to build 3,000 new council houses over the next two years. Housing minister John Healey has initiated the 'dismantling' of the housing finance system.

A genome-wide association study is conducted for the identification of the novel common variants that are associated with the circulating carotenoid levels and known lipid variants associated with [alpha]-tocopherol levels. The common variation taking place in the [beta]-carotene 15,15'-monooxygenase 1 gene is shown to affect the circulating levels of carotenoids.

The article discusses the results obtained from several different population-based genome-wide association studies of the plasma liver-enzyme levels in three different populations. The analysis reveals six loci that influence the plasma levels, hence providing candidate genes for several liver diseases.

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.14.8%) and effects of up to 2centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 12centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways., Author(s): Eirini Marouli [1]; Mariaelisa Graff [2]; Carolina Medina-Gomez [3, 4]; Ken Sin Lo [5]; Andrew R. Wood [6]; Troels R. Kjaer [7]; Rebecca S. Fine [8, 9, 10]; Yingchang [...]

A natural experiment on casino style gambling in 20 Kentucky counties since 1993 showed that gambling affects the number of bankruptcy filings. It was observed that bankruptcy increased in areas that are near gambling facilities. The influence of access to gambling on personal bankruptcies is discussed.

Author(s): The Wellcome Trust Case Control Consortium; Management Committee; Paul R. Burton [1]; David G. Clayton [2]; Lon R. Cardon [3]; Nick Craddock [4]; Panos Deloukas [5]; Audrey Duncanson [6]; [...]

Author(s): The Wellcome Trust Case Control Consortium; Management Committee; Paul R. Burton [1]; David G. Clayton [2]; Lon R. Cardon [3]; Nick Craddock [4]; Panos Deloukas [5]; Audrey Duncanson [6]; [...]

Background Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Methods and Findings Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 x 10.sup.-8). The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 x 10.sup.-25 ), encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 x 10.sup.-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 x 10.sup.-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 x 10.sup.-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Conclusions Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes., Author(s): Luca A. Lotta 1, Robert A. Scott 1, Stephen J. Sharp 1, Stephen Burgess 2, Jian'an Luan 1, Therese Tillin 3, Amand F. Schmidt 3, Fumiaki Imamura 1, Isobel [...]

Author(s): Momoko Horikoshi [1, 2]; Robin N. Beaumont [3]; Felix R. Day [4]; Nicole M. Warrington [5, 6]; Marjolein N. Kooijman [7, 8, 9]; Juan Fernandez-Tajes [1]; Bjarke Feenstra [10]; [...]

I. INTRODUCTION Despite the obviously theological nature of much of John Locke's writings, until recently that aspect of his work was largely ignored. His Christianity has often been seen as [...]

The government's plans to introduce a swathe of measures to reshape the housing finance system for local councils are discussed. Restructuring of debt will be available only to councils who set up management organizations and get a three-star rating from the Audit Commission.

Thomas F. Malone--former AMS president, recipient of the Losey Award in 1960 and the Charles Franklin Brooks Award in 1964, and Honorary AMS Member--passed away at his home in West [...]

The following article is both a reminder to those interested in the development of the doctrine of universal salvation that it has a long history, and an exercise in historiography of Karl Rahner's relationship to a seventeenth century Spanish Jesuit theologian, Juan Martinez de Ripalda. Rahner's thesis known as the 'supernatural existential' has Jesuit antecedents in the thought of Ripalda and his magnum opus entitled De ente supernaturali. After some historical contextualization of Ripalda we will focus on Rahner and offer possible reasons why the 'Molinist' thought of Ripalda with respect to the possibility of salvation for non-Christian persons was so important for his own work. The article will then provide a critical study of Rahner's reading of Ripalda and point out some key areas of difference in theological approach between the two Jesuits who, almost four hundred years ago, asked similar questions and came to the same answers using very different methodologies.

THE 'IRANIAN AREA' IS geographically cohesive, though its exact boundaries are rendered fuzzy by history and ethnology; conceptually, the term is vaguer, yet better merited. The highlands stretching across the [...]

Svante Arrhenius was considered the forerunner of modern climate research programs with his studies on carbon dioxide and glacial cycles. The Swede, who united the two issues in 1894, preceded the 1970s national climate research programs in terms of insight and quantitative findings. A book on Arrhenius' life, entitled 'The Legacy of Svante Arrhenius - Understanding the Greenhouse Effect', serves as a fitting monument to the accomplishments of the Swede in the field of interdisciplinary research on the climate system.

Background C-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal. Methods and Findings We performed Mendelian randomization (MR) analyses using two genetic risk scores (GRSs) as instrumental variables (IVs). The first GRS consisted of four single nucleotide polymorphisms (SNPs) in the CRP gene (GRS.sub.CRP ), and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study (GWAS) to date (GRS.sub.GWAS). To optimize power, we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes, with up to 123,865 participants per outcome from populations of European ancestry. We performed heterogeneity tests to disentangle the pleiotropic effect of IVs. A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant. An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association, yet to be confirmed. The strengths (F-statistics) of the IVs were 31.92-3,761.29 and 82.32-9,403.21 for GRS.sub.CRP and GRS.sub.GWAS, respectively. CRP GRS.sub.GWAS showed a statistically significant protective relationship of a 10% genetically elevated CRP level with the risk of schizophrenia (odds ratio [OR] 0.86 [95% CI 0.79-0.94]; p < 0.001). We validated this finding with individual-level genotype data from the schizophrenia GWAS (OR 0.96 [95% CI 0.94-0.98]; p < 1.72 x 10.sup.-6). Further, we found that a standardized CRP polygenic risk score (CRP.sub.PRS) at p-value thresholds of 1 x 10.sup.-4, 0.001, 0.01, 0.05, and 0.1 using individual-level data also showed a protective effect (OR < 1.00) against schizophrenia; the first CRP.sub.PRS (built of SNPs with p < 1 x 10.sup.-4) showed a statistically significant (p < 2.45 x 10.sup.-4) protective effect with an OR of 0.97 (95% CI 0.95-0.99). The CRP GRS.sub.GWAS showed that a 10% increase in genetically determined CRP level was significantly associated with coronary artery disease (OR 0.88 [95% CI 0.84-0.94]; p < 2.4 x 10.sup.-5) and was nominally associated with the risk of inflammatory bowel disease (OR 0.85 [95% CI 0.74-0.98]; p < 0.03), Crohn disease (OR 0.81 [95% CI 0.70-0.94]; p < 0.005), psoriatic arthritis (OR 1.36 [95% CI 1.00-1.84]; p < 0.049), knee osteoarthritis (OR 1.17 [95% CI 1.01-1.36]; p < 0.04), and bipolar disorder (OR 1.21 [95% CI 1.05-1.40]; p < 0.007) and with an increase of 0.72 (95% CI 0.11-1.34; p < 0.02) mm Hg in systolic blood pressure, 0.45 (95% CI 0.06-0.84; p < 0.02) mm Hg in diastolic blood pressure, 0.01 ml/min/1.73 m.sup.2 (95% CI 0.003-0.02; p < 0.005) in estimated glomerular filtration rate from serum creatinine, 0.01 g/dl (95% CI 0.0004-0.02; p < 0.04) in serum albumin level, and 0.03 g/dl (95% CI 0.008-0.05; p < 0.009) in serum protein level. However, after adjustment for heterogeneity, neither GRS showed a significant effect of CRP level (at p < 0.0016) on any of these outcomes, including coronary artery disease, nor on the other 20 complex outcomes studied. Our study has two potential limitations: the limited variance explained by our genetic instruments modeling CRP levels in blood and the unobserved bias introduced by the use of summary statistics in our MR analyses. Conclusions Genetically elevated CRP levels showed a significant potentially protective causal relationship with risk of schizophrenia. We observed nominal evidence at an observed p < 0.05 using either GRS.sub.CRP or GRS.sub.GWAS -with persistence after correction for heterogeneity-for a causal relationship of elevated CRP levels with psoriatic osteoarthritis, rheumatoid arthritis, knee osteoarthritis, systolic blood pressure, diastolic blood pressure, serum albumin, and bipolar disorder. These associations remain yet to be confirmed. We cannot verify any causal effect of CRP level on any of the other common somatic and neuropsychiatric outcomes investigated in the present study. This implies that interventions that lower CRP level are unlikely to result in decreased risk for the majority of common complex outcomes., Author(s): Bram. P. Prins 1,2,*, Ali Abbasi 1,3,4, Anson Wong 5,6, Ahmad Vaez 1,7, Ilja Nolte 1, Nora Franceschini 8, Philip E. Stuart 9, Javier Guterriez Achury 10, Vanisha Mistry [...]

[Editor's note: Some 350 years before Karl Rahner formulated his views on the supernatural existential, a Jesuit theologian from the University of Salamanca, Juan Martinez Ripalda, produced a coherent theory to provide theological support for the possibility of salvation for all. This theory rested on three core hermeneutical principles: 'active' obediential potency in the human person, the supernatural elevation of every moral act irrespective of its context, and 'wide faith.'], Since The Second Vatican Council, Catholics have committed themselves to dialogue not only with regard to other Christian churches but also with members of other living faiths. A great deal [...]

Two books on climate change and the effects of the El Nino phenomenon on society and climate have come at a most propitious time. The year 1997 highlighted news on global warming, storms, droughts and rising seas and culminated in a gathering at Kyoto, Japan. This sudden focus on the weather and climate reveals their importance on the economy and society, particularly the future generations. Thus, the books offer analyses to help people be the conscientious stewards of humanity's future.