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451.
452.
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453.
  • Mataix-Cols, David, et al. (författare)
  • Familial Risks of Tourette Syndrome and Chronic Tic Disorders A Population-Based Cohort Study
  • 2015
  • Ingår i: JAMA psychiatry. - Chicago, USA : American Medical Association. - 2168-6238. ; 72:8, s. 787-793
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Tic disorders, including Tourette syndrome (TS) and chronic tic disorders (CTDs), are assumed to be strongly familial and heritable. Although gene-searching efforts are well under way, precise estimates of familial risk and heritability are lacking. Previous controlled family studies were small and typically conducted within specialist clinics, resulting in potential ascertainment biases. They were also underpowered to disentangle genetic from environmental factors that contribute to the observed familiality. Twin studies have been either very small or based on parent-reported tics in population-based (nonclinical) twin samples.Objective: To provide unbiased estimates of familial risk and heritability of tic disorders at the population level.Design, setting, and participants: In this population cohort, multigenerational family study, we used a validated algorithm to identify 4826 individuals diagnosed as having TS or CTDs (76.2% male) in the Swedish National Patient Register from January 1, 1969, through December 31, 2009.Main outcomes and measures: We studied risks for TS or CTDs in all biological relatives of probands compared with relatives of unaffected individuals (matched on a 1:10 ratio) from the general population. Structural equation modeling was used to estimate the heritability of tic disorders.Results: The risk for tic disorders among relatives of probands with tic disorders increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives (odds ratio [OR], 18.69; 95% CI, 14.53-24.05) were significantly higher than for second-degree relatives (OR, 4.58; 95% CI, 3.22-6.52) and third-degree relatives (OR, 3.07; 95% CI, 2.08-4.51). First-degree relatives at similar genetic distances (eg, parents, siblings, and offspring) had similar risks for tic disorders despite different degrees of shared environment. The risks for full siblings (50% genetic similarity; OR, 17.68; 95% CI, 12.90-24.23) were significantly higher than those for maternal half siblings (25% genetic similarity; OR, 4.41; 95% CI, 2.24-8.67) despite similar environmental exposures. The heritability of tic disorders was estimated to be 0.77 (95% CI, 0.70-0.85). There were no differences in familial risk or heritability between male and female patients.Conclusions and relevance: Tic disorders, including TS and CTDs, cluster in families primarily because of genetic factors and appear to be among the most heritable neuropsychiatric conditions.
454.
  • McArdle, Patrick F., et al. (författare)
  • Agreement between TOAST and CCS ischemic stroke classification The NINDS SiGN Study
  • 2014
  • Ingår i: Neurology. - American Academy of Neurology. - 1526-632X. ; 83:18, s. 1653-1660
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The objective of this study was to assess the level of agreement between stroke subtype classifications made using the Trial of Org 10172 Acute Stroke Treatment (TOAST) and Causative Classification of Stroke (CCS) systems. Methods: Study subjects included 13,596 adult men and women accrued from 20 US and European genetic research centers participating in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN). All cases had independently classified TOAST and CCS stroke subtypes. Kappa statistics were calculated for the 5 major ischemic stroke subtypes common to both systems. Results: The overall agreement between TOAST and CCS was moderate (agreement rate, 70%; kappa = 0.59, 95% confidence interval [CI] 0.58-0.60). Agreement varied widely across study sites, ranging from 28% to 90%. Agreement on specific subtypes was highest for large-artery atherosclerosis (kappa = 0.71, 95% CI 0.69-0.73) and lowest for small-artery occlusion (kappa = 0.56, 95% CI 0.54-0.58). Conclusion: Agreement between TOAST and CCS diagnoses was moderate. Caution is warranted when comparing or combining results based on the 2 systems. Replication of study results, for example, genome-wide association studies, should utilize phenotypes determined by the same classification system, ideally applied in the same manner.
455.
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456.
  • McMillan, Paul J., et al. (författare)
  • Improved distances and ages for stars common to TGAS and RAVE
  • 2018
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - Oxford University Press. - 0035-8711. ; 477:4, s. 5279-5300
  • Tidskriftsartikel (refereegranskat)abstract
    • We combine parallaxes from the first Gaia data release with the spectrophotometric distance estimation framework for stars in the fifth RAVE survey data release. The combined distance estimates aremore accurate than either determination in isolation - uncertainties are on average two times smaller than for RAVE-only distances (three times smaller for dwarfs), and 1.4 times smaller than TGAS parallax uncertainties (two times smaller for giants). We are also able to compare the estimates from spectrophotometry to those from Gaia, and use this to assess the reliability of both catalogues and improve our distance estimates. We find that the distances to the lowest log g stars are, on average, overestimated and caution that they may not be reliable. We also find that it is likely that the Gaia random uncertainties are smaller than the reported values. As a by-product we derive ages for the RAVE stars, many with relative uncertainties less than 20 per cent. These results for 219 566 RAVE sources have been made publicly available, and we encourage their use for studies that combine the radial velocities provided by RAVE with the proper motions provided by Gaia. A sample that we believe to be reliable can be found by taking only the stars with the flag notification 'flag_any=0'.
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457.
  • Mee, Paul, et al. (författare)
  • Determinants of the risk of dying of HIV/AIDS in a rural South African community over the period of the decentralised roll-out of antiretroviral therapy a longitudinal study
  • 2014
  • Ingår i: Global Health Action. - Taylor & Francis. - 1654-9716. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Antiretroviral treatment (ART) has significantly reduced HIV mortality in South Africa. The benefits have not been experienced by all groups. Here we investigate the factors associated with these inequities.DESIGN: This study was located in a rural South African setting and used data collected from 2007 to 2010, the period when decentralised ART became available. Approximately one-third of the population were of Mozambican origin. There was a pattern of repeated circular migration between urban areas and this community. Survival analysis models were developed to identify demographic, socioeconomic, and spatial risk factors for HIV mortality.RESULTS: Among the study population of 105,149 individuals, there were 2,890 deaths. The HIV/TB mortality rate decreased by 27% between 2007-2008 and 2009-2010. For other causes of death, the reduction was 10%. Bivariate analysis found that the HIV/TB mortality risk was lower for: those living within 5 km of the Bhubezi Community Health Centre; women; young adults; in-migrants with a longer period of residence; permanent residents; and members of households owning motorised transport, holding higher socioeconomic positions, and with higher levels of education. Multivariate modelling showed, in addition, that those with South Africa as their country of origin had an increased risk of HIV/TB mortality compared to those with Mozambican origins. For males, those of South African origin, and recent in-migrants, the risk of death associated with HIV/TB was significantly greater than that due to other causes.CONCLUSIONS: In this community, a combination of factors was associated with an increased risk of dying of HIV/TB over the period of the roll-out of ART. There is evidence for the presence of barriers to successful treatment for particular sub-groups in the population, which must be addressed if the recent improvements in population-level mortality are to be maintained.
458.
  • Moore, Paul A., et al. (författare)
  • Assessing the peatland hummock-hollow classification framework using high-resolution elevation models implications for appropriate complexity ecosystem modeling
  • 2019
  • Ingår i: Biogeosciences. - COPERNICUS GESELLSCHAFT MBH. - 1726-4170 .- 1726-4189. ; 16:18, s. 3491-3506
  • Tidskriftsartikel (refereegranskat)abstract
    • The hummock-hollow classification framework used to categorize peatland ecosystem microtopography is pervasive throughout peatland experimental designs and current peatland ecosystem modeling approaches. However, identifying what constitutes a representative hummock-hollow pair within a site and characterizing hummock-hollow variability within or between peatlands remains largely unassessed. Using structure from motion (SfM), high-resolution digital elevation models (DEMs) of hummock-hollow microtopography were used to (1) examine how much area needs to be sampled to characterize site-level microtopographic variation; and (2) examine the potential role of microtopographic shape/structure on biogeochemical fluxes using plot-level data from nine northern peatlands. To capture 95% of site-level microtopographic variability, on average, an aggregate sampling area of 32 m(2) composed of 10 randomly located plots was required. Both site(i.e. transect data) and plot-level (i.e. SfM-derived DEM) results show that microtopographic variability can be described as a fractal at the submeter scale, where contributions to total variance are very small below a 0.5 m length scale. Microtopography at the plot level was often found to be non-bimodal, as assessed using a Gaussian mixture model (GMM). Our findings suggest that the non-bimodal distribution of microtopography at the plot level may result in an undersampling of intermediate topographic positions. Extended to the modeling domain, an underrepresentation of intermediate microtopographic positions is shown to lead to potentially large flux biases over a wide range of water table positions for ecosystem processes which are non-linearly related to water and energy availability at the moss surface. Moreover, our simple modeling results suggest that much of the bias can be eliminated by representing microtopography with several classes rather than the traditional two (i.e. hummock/hollow). A range of tools examined herein can be used to easily parameterize peatland models, from GMMs used as simple transfer functions to spatially explicit fractal landscapes based on simple power-law relations between microtopographic variability and scale.
459.
  • Navarese, Eliano Pio, et al. (författare)
  • Drug-coated balloons in treatment of in-stent restenosis : a meta-analysis of randomised controlled trials
  • 2013
  • Ingår i: Clinical Research in Cardiology. - 1861-0684 .- 1861-0692. ; 102:4, s. 279-287
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Drug-coated balloons (DCBs) have been developed for the percutaneous treatment of coronary artery disease. An initial focus has been the management of in-stent restenosis (ISR) but randomised controlled trials (RCTs) have been small and powered only for angiographic endpoints.OBJECTIVE:The aim of the work was to assess the clinical and angiographic outcomes of patients treated for ISR with DCB versus control (balloon angioplasty or drug-eluting stents) by a meta-analysis of RCTs.METHODS: A comprehensive search was performed of RCTs where patients with ISR were randomly assigned to either DCB or alternative coronary intervention. Outcome measurements were death, myocardial infarction (MI), target lesion revascularisation (TLR), binary definition of restenosis and in-lesion late luminal loss (LLL).RESULTS: Four studies were identified that fulfilled the inclusion criteria. Pooled odds ratios (ORs) were calculated for patients treated for ISR (n = 399). Mean follow-up duration was 14.5 months. DCBs were associated with lower rates of TLR [8.8 vs. 29.7 % OR (95 % confidence interval, CI) 0.20 (0.11-0.36), p < 0.0001], binary restenosis [10.3 vs. 41.3 % OR (95 % CI) 0.13 (0.07-0.24), p < 0.00001] and MI [0.5 vs. 3.8 %, OR (95 % CI) 0.21 (0.04-1.00), p = 0.05]. No significant heterogeneity was identified.CONCLUSION: Drug-coated balloons appear to be effective versus control in reducing TLR and possibly MI versus balloon angioplasty or drug-eluting stents in the management of ISR.
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460.
  • Nazarian, Arpi, et al. (författare)
  • Inhibition of Circulating Dipeptidyl Peptidase 4 Activity in Patients with Metastatic Prostate Cancer
  • 2014
  • Ingår i: Molecular & Cellular Proteomics. - American Society for Biochemistry and Molecular Biology. - 1535-9484. ; 13:11, s. 3082-3096
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer is responsible for many deaths and is a major source of healthcare expenditures. The identification of new, non-invasive biomarkers might allow improvement of the direct diagnostic or prognostic ability of already available tools. Here, we took the innovative approach of interrogating the activity of exopeptidases in the serum of cancer patients with the aim of establishing a distinction based on enzymatic function, instead of simple protein levels, as a means to biomarker discovery. We first analyzed two well-characterized mouse models of prostate cancer, each with a distinct genetic lesion, and established that broad exopeptidase and targeted aminopeptidase activity tests reveal proteolytic changes associated with tumor development. We also describe new peptide-based freeze-frame reagents uniquely suited to probe the altered balance of selected aminopeptidases, as opposed to the full array of exopeptidases, and/or their modulators in patient serum or plasma. One particular proteolytic activity was impaired in animals with aggressive disease relative to cancer-free littermates. We identified the protease in question as dipeptidyl peptidase 4 (DPP4) by analyzing selected knockout mice and evaluating the effect of specific inhibitors. DPP4 activity was also reduced in the sera of patients with metastatic prostate cancer relative to patients with localized disease or healthy controls. However, no significant differences in DPP4 serum levels were observed, which established the loss of activity as the result of impaired enzymatic function. Biochemical analysis indicated that reduced activity was the result not of post-translational modifications or allosteric changes, but instead of a low-molecular-weight inhibitor. After we adjusted for age and total prostate-specific antigen, reduced DPP4 activity remained a significant predictor of cancer status. The results of this proof-of-principle study suggest that DPP4 activity might be a potential blood-based indicator of the presence of metastatic cancer of prostatic origin, either by itself or, more likely, as a means to improve the sensitivity and specificity of existing markers.
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