100 research outputs found
Better the donor you know?:A qualitative study of renal patients' views on ‘altruistic’ live-donor kidney transplantation
AbstractBackgroundIn the UK there is a short-fall between individuals requiring a renal transplant and kidneys available for transplantation. Non-directed ‘altruistic’ living kidney donation has emerged as a strategy for bridging this gap between supply and demand, with the number increasing each year.ObjectiveThis study aimed to explore the views of potential recipients towards non-directed ‘altruistic’ live-donor kidney transplantation.MethodsSemi-structured interviews with 32 UK deceased-donor kidney transplant recipients were performed. Interviews explored willingness to consider directed and non-directed live-donor kidney transplants (LDKTs). Interviews were recorded, transcribed verbatim and transcripts were analysed using the constant comparison method described in Grounded Theory.ResultsFor those not willing to accept a non-directed ‘altruistic’ LDKT, the following themes were identified: i) Prioritising other recipients above self; ii) Fear of acquiring an unknown donor's characteristics, and iii) Concern for the donor – unnecessary risk. For those willing to accept a non-directed ‘altruistic’ LDKT the following themes were identified: iv) Prioritising known above unknown persons, v) Belief that they are as deserving as other potential recipients, and vi) Advantages of a LDKT.ConclusionsDrawing on ‘gift exchange theory’, this study contributes to our understanding of the experience of the intended recipient of a gift. The anonymity of the donor-recipient appears to be seen as a benefit of non-directed ‘altruistic’ live-donor transplants, freeing recipients from the obligations of the gift. However, those who feel unworthy of the ‘gifted transplant’ are concerned about the donor and by the lack of opportunity for direct reciprocity. Highlighting the ‘reciprocal benefits’ reported by donors may allow individuals whose preference is a live-donor transplant to accept one if offered. These insights provide the transplant community with targets for intervention, through which the concerns of potential recipients might be addressed
Real-Time Detection and Rapid Multiwavelength Follow-up Observations of a Highly Subluminous Type II-P Supernova from the Palomar Transient Factory Survey
The Palomar Transient Factory (PTF) is an optical wide-field variability
survey carried out using a camera with a 7.8 square degree field of view
mounted on the 48-in Oschin Schmidt telescope at Palomar Observatory. One of
the key goals of this survey is to conduct high-cadence monitoring of the sky
in order to detect optical transient sources shortly after they occur. Here, we
describe the real-time capabilities of the PTF and our related rapid
multiwavelength follow-up programs, extending from the radio to the gamma-ray
bands. We present as a case study observations of the optical transient
PTF10vdl (SN 2010id), revealed to be a very young core-collapse (Type II-P)
supernova having a remarkably low luminosity. Our results demonstrate that the
PTF now provides for optical transients the real-time discovery and
rapid-response follow-up capabilities previously reserved only for high-energy
transients like gamma-ray bursts.Comment: ApJ, in press; all spectroscopic data available from the Weizmann
Institute of Science Experimental Astrophysics Spectroscopy System (WISEASS;
http://www.weizmann.ac.il/astrophysics/wiseass/
Metabolic Profiling of Adiponectin Levels in Adults
Background - Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile.
Methods and Results - We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population.
Conclusions - Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant
The Association of C-Reactive Protein and CRP Genotype with Coronary Heart Disease: Findings from Five Studies with 4,610 Cases amongst 18,637 Participants
Background: It is unclear whether C-reactive protein (CRP) is causally related to coronary heart disease (CHD). Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864) and CHD risk in the largest study to date of this association.Methods and Results: We estimated the association of CRP genetic variant +1444C>T (rs1130864) with CRP levels and with CHD in five studies and then pooled these analyses (N= 18,637 participants amongst whom there were 4,610 cases). CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass) whereas genotype (rs1130864) was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95% CI: 1.06, 1.21), and after further adjustment for confounding factors it was 1.07 (95% CI: 1.02, 1.13). Genotype (rs1130864) was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95% CI: 1.15, 1.28) and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95% CI: 1.11, 1.18), with no strong evidence in either analyses of between study heterogeneity (I-2 = 0%, p>0.9 for both analyses). There was no association of genotype (rs1130864) with CHD: pooled odds ratio 1.01 (95% CI: 0.88, 1.16) comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95% CI: 0.90, 1.03) per additional T allele (I-2<7.5%, p. 0.6 for both meta-analyses). An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD) suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95% CI: 0.61, 1.80).Conclusions: We found no association of a genetic variant, which is known to be related to CRP levels, (rs1130864) and having CHD. These findings do not support a causal association between circulating CRP and CHD risk, but very large, extended, genetic association studies would be required to rule this out
PTF10iya: A short-lived, luminous flare from the nuclear region of a star-forming galaxy
We present the discovery and characterisation of PTF10iya, a short-lived (dt
~ 10 d, with an optical decay rate of ~ 0.3 mag per d), luminous (M_g ~ -21
mag) transient source found by the Palomar Transient Factory. The
ultraviolet/optical spectral energy distribution is reasonably well fit by a
blackbody with T ~ 1-2 x 10^4 K and peak bolometric luminosity L_BB ~ 1-5 x
10^44 erg per s (depending on the details of the extinction correction). A
comparable amount of energy is radiated in the X-ray band that appears to
result from a distinct physical process. The location of PTF10iya is consistent
with the nucleus of a star-forming galaxy (z = 0.22405 +/- 0.00006) to within
350 mas (99.7 per cent confidence radius), or a projected distance of less than
1.2 kpc. At first glance, these properties appear reminiscent of the
characteristic "big blue bump" seen in the near-ultraviolet spectra of many
active galactic nuclei (AGNs). However, emission-line diagnostics of the host
galaxy, along with a historical light curve extending back to 2007, show no
evidence for AGN-like activity. We therefore consider whether the tidal
disruption of a star by an otherwise quiescent supermassive black hole may
account for our observations. Though with limited temporal information,
PTF10iya appears broadly consistent with the predictions for the early
"super-Eddington" phase of a solar-type star disrupted by a ~ 10^7 M_sun black
hole. Regardless of the precise physical origin of the accreting material, the
large luminosity and short duration suggest that otherwise quiescent galaxies
can transition extremely rapidly to radiate near the Eddington limit; many such
outbursts may have been missed by previous surveys lacking sufficient cadence.Comment: 18 pages, 8 figures; revised following referee's comment
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
Association of the Type 2 Diabetes Mellitus Susceptibility Gene, TCF7L2, with Schizophrenia in an Arab-Israeli Family Sample
Many reports in different populations have demonstrated linkage of the 10q24–q26 region to schizophrenia, thus encouraging further analysis of this locus for detection of specific schizophrenia genes. Our group previously reported linkage of the 10q24–q26 region to schizophrenia in a unique, homogeneous sample of Arab-Israeli families with multiple schizophrenia-affected individuals, under a dominant model of inheritance. To further explore this candidate region and identify specific susceptibility variants within it, we performed re-analysis of the 10q24-26 genotype data, taken from our previous genome-wide association study (GWAS) (Alkelai et al, 2011). We analyzed 2089 SNPs in an extended sample of 57 Arab Israeli families (189 genotyped individuals), under the dominant model of inheritance, which best fits this locus according to previously performed MOD score analysis. We found significant association with schizophrenia of the TCF7L2 gene intronic SNP, rs12573128, (p = 7.01×10−6) and of the nearby intergenic SNP, rs1033772, (p = 6.59×10−6) which is positioned between TCF7L2 and HABP2. TCF7L2 is one of the best confirmed susceptibility genes for type 2 diabetes (T2D) among different ethnic groups, has a role in pancreatic beta cell function and may contribute to the comorbidity of schizophrenia and T2D. These preliminary results independently support previous findings regarding a possible role of TCF7L2 in susceptibility to schizophrenia, and strengthen the importance of integrating linkage analysis models of inheritance while performing association analyses in regions of interest. Further validation studies in additional populations are required
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Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors
Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors.
METHODS:
The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country.
RESULTS:
There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10- 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10- 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10- 6 and P = 3 × 10- 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10- 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes.
CONCLUSION:
In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts
The Polygenic and Monogenic Basis of Blood Traits and Diseases
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases
Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study
INTRODUCTION:
Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2.
METHODS:
We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI.
RESULTS:
Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging.
DISCUSSION:
The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration
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