| 121. |
- Hivert, Marie-France, et al.
(författare)
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Updated Genetic Score Based on 34 Confirmed Type 2 Diabetes Loci Is Associated With Diabetes Incidence and Regression to Normoglycemia in the Diabetes Prevention Program
- 2011
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 60:4, s. 1340-1348
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Over 30 loci have been associated with risk of type 2 diabetes at genome-wide statistical significance. Genetic risk scores (GRSs) developed from these loci predict diabetes in the general population. We tested if a GRS based on an updated list of 34 type 2 diabetes-associated loci predicted progression to diabetes or regression toward normal glucose regulation (NGR) in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS We genotyped 34 type 2 diabetes-associated variants in 2,843 DPP participants at high risk of type 2 diabetes from five ethnic groups representative of the U.S. population, who had been randomized to placebo, metformin, or lifestyle intervention. We built a GRS by weighting each risk allele by its reported effect size on type 2 diabetes risk and summing these values. We tested its ability to predict diabetes incidence or regression to NGR in models adjusted for age, sex, ethnicity, waist circumference, and treatment assignment. RESULTS lit multivariate-adjusted models, the GRS was significantly associated with increased risk of progression to diabetes (hazard ratio [HR] = 1.02 per risk allele [95% CI 1.00-1.05]; P = 0.03) and a lower probability of regression to NGR (HR = 0.95 per risk allele [95% CI 0.93-0.981; P < 0.0001). At baseline, a higher GRS was associated with a lower insulinogenic index (P < 0.001), confirming an impairment in beta-cell function. We detected no significant interaction between GRS and treatment, but the lifestyle intervention was effective in the highest quartile of ORS (P < 0.0001). CONCLUSIONS A high GRS is associated with increased risk of developing diabetes and lower probability of returning to NGR in high-risk individuals, but a lifestyle intervention attenuates this risk. Diabetes 60:1340-1348, 2011
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| 122. |
- Jakobsson, Martin, et al.
(författare)
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The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0
- 2012
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 39
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Tidskriftsartikel (refereegranskat)abstract
- The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arctic science activities, for example, by providing constraint for ocean circulation models and the means to define and formulate hypotheses about the geologic origin of Arctic undersea features. IBCAO Version 3.0 represents the largest improvement since 1999 taking advantage of new data sets collected by the circum-Arctic nations, opportunistic data collected from fishing vessels, data acquired from US Navy submarines and from research ships of various nations. Built using an improved gridding algorithm, this new grid is on a 500 meter spacing, revealing much greater details of the Arctic seafloor than IBCAO Version 1.0 (2.5 km) and Version 2.0 (2.0 km). The area covered by multibeam surveys has increased from similar to 6% in Version 2.0 to similar to 11% in Version 3.0. Citation: Jakobsson, M., et al. (2012), The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0, Geophys. Res. Lett., 39, L12609, doi:10.1029/2012GL052219.
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| 123. |
- Kõljalg, Urmas, et al.
(författare)
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Towards a unified paradigm for sequence-based identification of fungi.
- 2013
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Ingår i: Molecular ecology. - : Wiley. - 1365-294X .- 0962-1083. ; 22:21, s. 5271-7
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear ribosomal internal transcribed spacer (ITS) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database (http://unite.ut.ee) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. Hymenoscyphus pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third-party annotation effort. We introduce the term 'species hypothesis' (SH) for the taxa discovered in clustering on different similarity thresholds (97-99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released (http://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web-based sequence management system in UNITE.
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| 124. |
- Mee, Paul, et al.
(författare)
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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
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Ingår i: Global Health Action. - : Taylor & Francis. - 1654-9716 .- 1654-9880. ; 7
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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.
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| 125. |
- Navarese, Eliano Pio, et al.
(författare)
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Drug-coated balloons in treatment of in-stent restenosis : a meta-analysis of randomised controlled trials
- 2013
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Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 102:4, s. 279-287
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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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| 126. |
- Nazarian, Arpi, et al.
(författare)
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Inhibition of Circulating Dipeptidyl Peptidase 4 Activity in Patients with Metastatic Prostate Cancer
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 13:11, s. 3082-3096
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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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| 127. |
- Papadopoulos, Nikolaos G, et al.
(författare)
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Research needs in allergy: an EAACI position paper, in collaboration with EFA.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.
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| 128. |
- Park, Yikyung, et al.
(författare)
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Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer : a pooled analysis of prospective cohort studies
- 2010
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 21:11, s. 1745-1757
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer. Using the primary data from 13 cohort studies, we estimated study- and sex-specific relative risks (RR) with Cox proportional hazards models and subsequently pooled RRs using a random effects model. Among 676,141 men and women, 5,454 colon cancer cases were identified (7-20 years of follow-up across studies). Vitamin A, C, and E intakes from food only were not associated with colon cancer risk. For intakes from food and supplements (total), the pooled multivariate RRs (95% CI) were 0.88 (0.76-1.02, > 4,000 vs. a parts per thousand currency sign1,000 mu g/day) for vitamin A, 0.81 (0.71-0.92, > 600 vs. a parts per thousand currency sign100 mg/day) for vitamin C, and 0.78 (0.66-0.92, > 200 vs. a parts per thousand currency sign6 mg/day) for vitamin E. Adjustment for total folate intake attenuated these associations, but the inverse associations with vitamins C and E remained significant. Multivitamin use was significantly inversely associated with colon cancer risk (RR = 0.88, 95% CI: 0.81-0.96). Modest inverse associations with vitamin C and E intakes may be due to high correlations with folate intake, which had a similar inverse association with colon cancer. An inverse association with multivitamin use, a major source of folate and other vitamins, deserves further study.
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| 129. |
- Paul, James A
(författare)
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Civil society and the United Nations
- 2012
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Ingår i: Global Civil Society. - Uppsala : Uppsala universitet. - 9789197574181 ; , s. 63-82
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 130. |
- Ryvlin, Philippe, et al.
(författare)
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Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS) : a retrospective study
- 2013
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 12:10, s. 966-977
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Tidskriftsartikel (refereegranskat)abstract
- Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. Methods Between Jan 1,2008, and Dec 29,2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. Findings 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5.1 (95% CI 2.6-9.2) per 1000 patient-years, with a risk of 1.2 (0.6-2.1) per 10 000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. Interpretation SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time.
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