131 research outputs found
'What she told us made the world of difference': Carers perspectives of a hospice at home service
No full textCopyright @ 2013 Institut universitaire de gériatrie de Montréal. Posted with publisher's permission.This paper explores the expectations and needs of current and bereaved carers whose relatives
received care at home from a palliative care team. Aim: A hospice at home service was established in
2006 to provide patients with care in their own homes. We examined whether this model of care was helpful in
mitigating carers’ burden and in enabling terminally ill patients to be cared for and die at home. Methods: This
study utilized a survey and interviews. Participants were carers in the midwest of Ireland. Survey responses from 122 carers were analyzed using SPSS 18.0 (SPSS Inc., 2009); interviews with 15 carers were also conducted. Results: Carers’ expectations of the service were often exceeded, and quality of care dimensions were rated highly. Future improvements could include facilitating discussions on place of death and offering bereavement support. Conclusion: The service is supporting carers in facilitating their relatives’ choice to die at home.Atlantic Philanthropies and the Health Service Executiv
Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts
No full textBackground: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m 2 higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52610227 ). The BMI allele score was associated both with BMI (p = 6.30610262 ) and 25(OH)D (20.06% [95% CI 20.10 to 20.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p#8.07610257 for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: 24.2 [95% CI 27.1 to 21.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p$0.57 for both vitamin D scores).Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency
Polyphony and the anxiety of influence in the fiction of Henry James
No full textJames's fiction, especially in the Middle Phase, centres
on the figure of the artist and is characterized by, the two
interrelated aspects which previous criticism has largely
overlooked: the Bakhtinian 'polyphonic' -creation of
'author-thinkers'; and the conflict between ephebes and
precursors, for which Harold-Bloom's concept of 'the-anxiety of
influence' is the most illuminating model. Polyphony is the
narrative mode, and influence is the intra-artistic, theme.
These, as the Introduction to the thesis makes clear, are
rehearsed in James's inaugural novel, Roderick Hudson. Rowland
Mallet is an author-thinker, and his failure is caused by
authorial limitations. His monologism -is impaired by his
mistaking empathy for the authorial sympathy. Likewise,
Hudson's failure does not arise from a mercurial temperament,
but from a polyphonic shortcoming: not possessing the power of
fiction to contain the fiction of power in, his mentor. And the
relationships among the three artists - Gloriani, Hudson and
Singleton - perfectly exemplify the Bloomian-theme. It is these
two concepts, polyphony and influence, which are the major
preoccupation in the Middle Phase; as, the works chosen
demonstrate. These are a novella, a novel, and a number of
short stories all of which have been unjustifiably neglected.
Chapter One, on The Aspern Papers, argues that Tina Bordereau,
far from being, the artless victim seen by many critics,
actually challenges and defeats the narrator by the very form
of her narrative. Her 'realist' discourse undermines his
language of 'romance', and shows up its internal unstability.
Chapter Two is an extensive study of the critical reception of
The Tragic Muse. The most common areas of critical attention
have been its contemporary topicality, its relation to previous
novels on similar themes, and the possible genealogy of Gabriel
Nash. Those have all missed the core of the work. - Chapter Three
demonstrates how polyphony and the anxiety of influence make
the novel what it really is. Influence arises from the
juxtaposition of, and the wrestling between, artistic ephebes
and their precursors (Nick and Nash,, Miriam and Madame Carre).
The dialogic quality defined by Bakhtin is crucial to the
proper, and even-handed, characterization of all, the conflicts
in the novel. And since most of James's tales in the eighties
and nineties -are about 'masters - and acolytes, the anxiety of
influence remains central. Chapter Four is a study of 'The
Author of Beltraffiol' and 'The Lesson of the Master'. Again the
characters' manipulations are a crucial focus in a way that
G6rard Genette's terminology helps to illuminate. The fact that
the ephebe is the author-thinker emphasizes the inextricability
of the Bakhtinian and the Bloomian in James. Just as
polyphony offers a different focus for explicating the poetics
of James's fiction; so the ephebal conflict provides the basis
for a fresh perception of James's own artistic struggle
First in the Nation in Education : Final Report,1984.
No full textThis report is one step in an ongoing process of change and is a plea for commitment for high standards in education in Iowa. Contains the final reports of the six subcommittees as adopted by the Excellence in Education Task Force, and the five recommendations made by the Task Force
Prevalence, incidence and risk factors of epilepsy in older children in rural Kenya.
No full textBACKGROUND: There is little data on the burden or causes of epilepsy in developing countries, particularly in children living in sub-Saharan Africa. METHODS: We conducted two surveys to estimate the prevalence, incidence and risk factors of epilepsy in children in a rural district of Kenya. All children born between 1991 and 1995 were screened with a questionnaire in 2001 and 2003, and those with a positive response were then assessed for epilepsy by a clinician. Active epilepsy was defined as two or more unprovoked seizures with one in the last year. RESULTS: In the first survey 10,218 children were identified from a census, of whom 110 had epilepsy. The adjusted prevalence estimates of lifetime and active epilepsy were 41/1000 (95% CI: 31-51) and 11/1000 (95% CI: 5-15), respectively. Overall two-thirds of children had either generalized tonic-clonic and/or secondary generalized seizures. A positive history of febrile seizures (OR=3.01; 95% CI: 1.50-6.01) and family history of epilepsy (OR=2.55; 95% CI: 1.19-5.46) were important risk factors for active epilepsy. After the second survey, 39 children from the same birth cohort with previously undiagnosed epilepsy were identified, thus the incidence rate of active epilepsy is 187 per 100,000 per year (95% CI: 133-256) in children aged 6-12 years. CONCLUSIONS: There is a considerable burden of epilepsy in older children living in this area of rural Kenya, with a family history of seizures and a history of febrile seizures identified as risk factors for developing epilepsy
Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits
No full textNonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
No full textTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause
Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease
No full textThe polymorphism, KLF6-IVS1-27A, in the Krüppel-like factor 6 (KLF6) transcription factor gene enhances its splicing into antagonistic isoforms and is associated with delayed histological progression of nonalcoholic fatty liver disease (NAFLD). To explore a potential role for KLF6 in the development of insulin resistance, central to NAFLD pathogenesis, we genotyped KLF6-IVS1-27 in healthy subjects and assayed fasting plasma glucose (FPG) and insulin sensitivities. Furthermore, we quantified messenger RNA (mRNA) expression of KLF6 and glucokinase (GCK), as an important mediator of insulin sensitivity, in human livers and in liver tissues derived from a murine Klf6 knockdown model (DeltaKlf6). Klf6 overexpression studies in a mouse hepatocyte line were utilized to mechanistically link KLF6 with Gck promoter activity. KLF6-IVS1-27Gwt (i.e., less KLF6 splicing) was associated with stepwise increases in FPG and insulin and reduced hepatic insulin sensitivity. KLF6 binds to the liver-specific Gck promoter and activates a GCK promoter-reporter, identifying GCK as a KLF6 direct transcriptional target. Accordingly, in DeltaKlf6 hepatocytes Gck expression was reduced and stable transfection of Klf6 led to up-regulation of Gck. GCK and KLF6 mRNAs correlate directly in human NAFLD tissues and immunohistochemistry studies confirm falling levels of both KLF6 and GCK in fat-laden hepatocytes. In contrast to full-length KLF6, splice variant KLF6-SV1 increases in NAFLD hepatocytes and inversely correlates with glucokinase regulatory protein, which negatively regulates GCK activity. Conclusion: KLF6 regulation of GCK contributes to the development of hepatic insulin resistance. The KLF6-IVS1-27A polymorphism, which generates more KLF6-SV1, combats this, lowering hepatic insulin resistance and blood glucose.Lars P. Bechmann, Amalia Gastaldelli, Diana Vetter, Gillian L. Patman, Laura Pascoe, Rebekka A. Hannivoort, Ursula E. Lee, Isabel Fiel, Ursula Muñoz, Demetrio Ciociaro, Young-Min Lee, Emma Buzzigoli, Luca Miele, Kei Y. Hui, Elisabetta Bugianesi, Alastair D. Burt, Christopher P. Day, Andrea Mari, Loranne Agius, Mark Walker, Scott L. Friedman, and Helen L. Reeve
Disentangling the genetics of lean mass
No full textBackground: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass
Ultraviolet radiation suppresses obesity and symptoms of metabolic syndrome independently of vitamin d in mice fed a high-fat diet
No full textThe role of vitamin D in curtailing the development of obesity and comorbidities such as the metabolic syndrome (MetS) and type 2 diabetes has received much attention recently. However, clinical trials have failed to conclusively demonstrate the benefits of vitamin D supplementation. In most studies, serum 25-hydroxyvitamin D [25(OH)D] decreases with increasing BMI above normal weight. These low 25(OH)D levels may also be a proxy for reduced exposure to sunlight-derived ultraviolet radiation (UVR). Here we investigate whether UVR and/or vitamin D supplementation modifies the development of obesity and type 2 diabetes in a murine model of obesity. Long-term suberythemal and erythemal UVR significantly suppressed weight gain, glucose intolerance, insulin resistance, nonalcoholic fatty liver disease measures; and serum levels of fasting insulin, glucose, and cholesterol in C57BL/6 male mice fed a high-fat diet. However, many of the benefits of UVR were not reproduced by vitamin D supplementation. In further mechanistic studies, skin induction of the UVR-induced mediator nitric oxide (NO) reproduced many of the effects of UVR. These studies suggest that UVR (sunlight exposure) may be an effective means of suppressing the development of obesity and MetS, through mechanisms that are independent of vitamin D but dependent on other UVR-induced mediators such as NO.</p
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