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2.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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4.
  • Treat, Claire C., et al. (författare)
  • Widespread global peatland establishment and persistence over the last 130,000 y
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:11, s. 4822-4827
  • Tidskriftsartikel (refereegranskat)abstract
    • Glacial-interglacial variations in CO2 and methane in polar ice cores have been attributed, in part, to changes in global wetland extent, but the wetland distribution before the Last Glacial Maximum (LGM, 21 ka to 18 ka) remains virtually unknown. We present a study of global peatland extent and carbon (C) stocks through the last glacial cycle (130 ka to present) using a newly compiled database of 1,063 detailed stratigraphic records of peat deposits buried by mineral sediments, as well as a global peatland model. Quantitative agreement between modeling and observations shows extensive peat accumulation before the LGM in northern latitudes (> 40 degrees N), particularly during warmer periods including the last interglacial (130 ka to 116 ka, MIS 5e) and the interstadial (57 ka to 29 ka, MIS 3). During cooling periods of glacial advance and permafrost formation, the burial of northern peatlands by glaciers and mineral sediments decreased active peatland extent, thickness, and modeled C stocks by 70 to 90% from warmer times. Tropical peatland extent and C stocks show little temporal variation throughout the study period. While the increased burial of northern peats was correlated with cooling periods, the burial of tropical peat was predominately driven by changes in sea level and regional hydrology. Peat burial by mineral sediments represents a mechanism for long-term terrestrial C storage in the Earth system. These results show that northern peatlands accumulate significant C stocks during warmer times, indicating their potential for C sequestration during the warming Anthropocene.
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6.
  • Blom, Elin Susanne, et al. (författare)
  • Does APOE explain the linkage of Alzheimer’s disease to chromosome 19q13?
  • 2008
  • Ingår i: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-485X. ; 147B:6, s. 778-83
  • Tidskriftsartikel (refereegranskat)abstract
    • We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multi-point linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon 4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.
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7.
  • Blom, Elin Susanne, et al. (författare)
  • Further analysis of previously implicated linkage regions for Alzheimer’s disease in affected relative pairs
  • 2009
  • Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 10, s. 122-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Genome-wide linkage studies for Alzheimer's disease have implicated several chromosomal regions as potential loci for susceptibility genes. Methods: In the present study, we have combined a selection of affected relative pairs (ARPs) from the UK and the USA included in a previous linkage study by Myers et al. (Am J Med Genet, 2002), with ARPs from Sweden and Washington University. In this total sample collection of 397 ARPs, we have analyzed linkage to chromosomes 1, 9, 10, 12, 19 and 21, implicated in the previous scan. Results: The analysis revealed that linkage to chromosome 19q13 close to the APOE locus increased considerably as compared to the earlier scan. However, linkage to chromosome 10q21, which provided the strongest linkage in the previous scan could not be detected. Conclusion: The present investigation provides yet further evidence that 19q13 is the only chromosomal region consistently linked to Alzheimer's disease.
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8.
  • Byles, Julie E, et al. (författare)
  • Women's uptake of Medicare Benefits Schedule mental health items for general practitioners, psychologists and other allied mental health professionals.
  • 2011
  • Ingår i: The Medical journal of Australia. - 1326-5377. ; 194:4, s. 175-179
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To quantify women's uptake of Medicare Benefits Schedule mental health items, compare characteristics of women by mental health service use, and investigate the impact on Medicare costs.DESIGN, SETTING AND PARTICIPANTS: Analysis of linked survey data and Medicare records (November 2006 - December 2007) of 14 911 consenting participants of the Australian Longitudinal Study on Women's Health (ALSWH) across three birth cohorts (1921-1926 ["older cohort"], 1946-1951 ["mid-age cohort"], and 1973-1978 ["younger cohort"]).MAIN OUTCOME MEASURES: Uptake of mental health items; 36-Item Short Form Health Survey (SF-36) Mental Health Index scores from ALSWH surveys; and patient (out-of-pocket) and benefit (government) costs from Medicare data.RESULTS: A large proportion of women who reported mental health problems made no mental health claims (on the most recent survey, 88%, 90% and 99% of the younger, mid-age and older cohorts, respectively). Socioeconomically disadvantaged women were less likely to use the services. SF-36 Mental Health Index scores among women in the younger and mid-age cohorts were lowest for women who had accessed mental health items or self-reported a recent mental health condition. Mental health items are associated with higher costs to women and government.CONCLUSION: Although there has been rapid uptake of mental health items, uptake by women with mental health needs is low and there is potential socioeconomic inequity.
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9.
  • Chaney, Aisling M., et al. (författare)
  • Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD : a collaborative multi-modal study
  • 2021
  • Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:14, s. 6644-6667
  • Tidskriftsartikel (refereegranskat)abstract
    • Mouse models of Alzheimer's disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary tangles, despite only expressing APP and PSEN1 mutations, suggesting an improved modelling of AD hallmarks. Alterations in neuronal networks as well as learning performance and cognition tasks have been reported in this model, but none have combined a longitudinal, multimodal approach across multiple centres, which mimics the approaches commonly taken in clinical studies. We therefore aimed to further characterise the progression of AD-like pathology and cognition in the TgF344-AD rat from young-adults (6 months (m)) to mid- (12 m) and advanced-stage (18 m, 25 m) of the disease.Methods: TgF344-AD rats and wild-type (WT) littermates were imaged at 6 m, 12 m and 18 m with [18F]DPA-714 (TSPO, neuroinflammation), [18F]Florbetaben (Aβ) and [18F]ASEM (α7-nicotinic acetylcholine receptor) and with magnetic resonance spectroscopy (MRS) and with (S)-[18F]THK5117 (Tau) at 15 and 25 m. Behaviour tests were also performed at 6 m, 12 m and 18 m. Immunohistochemistry (CD11b, GFAP, Aβ, NeuN, NeuroChrom) and Tau (S)-[18F]THK5117 autoradiography, immunohistochemistry and Western blot were also performed.Results: [18F]DPA-714 positron emission tomography (PET) showed an increase in neuroinflammation in TG vs wildtype animals from 12 m in the hippocampus (+11%), and at the advanced-stage AD in the hippocampus (+12%), the thalamus (+11%) and frontal cortex (+14%). This finding coincided with strong increases in brain microgliosis (CD11b) and astrogliosis (GFAP) at these time-points as assessed by immunohistochemistry. In vivo [18F]ASEM PET revealed an age-dependent increase uptake in the striatum and pallidum/nucleus basalis of Meynert in WT only, similar to that observed with this tracer in humans, resulting in TG being significantly lower than WT by 18 m. In vivo [18F]Florbetaben PET scanning detected Aβ accumulation at 18 m, and (S)-[18F]THK5117 PET revealed subsequent Tau accumulation at 25m in hippocampal and cortical regions. Aβ plaques were low but detectable by immunohistochemistry from 6 m, increasing further at 12 and 18 m with Tau-positive neurons adjacent to Aβ plaques at 18 m. NeuroChrom (a pan neuronal marker) immunohistochemistry revealed a loss of neuronal staining at the Aβ plaques locations, while NeuN labelling revealed an age-dependent decrease in hippocampal neuron number in both genotypes. Behavioural assessment using the novel object recognition task revealed that both WT & TgF344-AD animals discriminated the novel from familiar object at 3 m and 6 m of age. However, low levels of exploration observed in both genotypes at later time-points resulted in neither genotype successfully completing the task. Deficits in social interaction were only observed at 3 m in the TgF344-AD animals. By in vivo MRS, we showed a decrease in neuronal marker N-acetyl-aspartate in the hippocampus at 18 m (-18% vs age-matched WT, and -31% vs 6 m TG) and increased Taurine in the cortex of TG (+35% vs age-matched WT, and +55% vs 6 m TG).Conclusions: This multi-centre multi-modal study demonstrates, for the first time, alterations in brain metabolites, cholinergic receptors and neuroinflammation in vivo in this model, validated by robust ex vivo approaches. Our data confirm that, unlike mouse models, the TgF344-AD express Tau pathology that can be detected via PET, albeit later than by ex vivo techniques, and is a useful model to assess and longitudinally monitor early neurotransmission dysfunction and neuroinflammation in AD.
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10.
  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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11.
  • Fogh, Isabella, et al. (författare)
  • A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis
  • 2014
  • Ingår i: Human Molecular Genetics. - Oxford : Oxford University Press. - 0964-6906 .- 1460-2083. ; 23:8, s. 2220-2231
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of mutations at familial loci for amyotrophic lateral sclerosis (ALS) has provided novel insights into the aetiology of this rapidly progressing fatal neurodegenerative disease. However, genome-wide association studies (GWAS) of the more common (90) sporadic form have been less successful with the exception of the replicated locus at 9p21.2. To identify new loci associated with disease susceptibility, we have established the largest association study in ALS to date and undertaken a GWAS meta-analytical study combining 3959 newly genotyped Italian individuals (1982 cases and 1977 controls) collected by SLAGEN (Italian Consortium for the Genetics of ALS) together with samples from Netherlands, USA, UK, Sweden, Belgium, France, Ireland and Italy collected by ALSGEN (the International Consortium on Amyotrophic Lateral Sclerosis Genetics). We analysed a total of 13 225 individuals, 6100 cases and 7125 controls for almost 7 million single-nucleotide polymorphisms (SNPs). We identified a novel locus with genome-wide significance at 17q11.2 (rs34517613 with P 1.11 10(8); OR 0.82) that was validated when combined with genotype data from a replication cohort (P 8.62 10(9); OR 0.833) of 4656 individuals. Furthermore, we confirmed the previously reported association at 9p21.2 (rs3849943 with P 7.69 10(9); OR 1.16). Finally, we estimated the contribution of common variation to heritability of sporadic ALS as 12 using a linear mixed model accounting for all SNPs. Our results provide an insight into the genetic structure of sporadic ALS, confirming that common variation contributes to risk and that sufficiently powered studies can identify novel susceptibility loci.
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12.
  • Fuller, Beth G, et al. (författare)
  • Active living--the perception of older people with chronic conditions
  • 2010
  • Ingår i: Chronic Illness. - : Sage Publications. - 1742-3953 .- 1745-9206. ; 6:4, s. 294-305
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To describe and understand factors which enhance and impede participation in physical activity for older adults with and without chronic illness and develop a framework of health behaviours for 'active living'.METHODS: A contrasting group framework was used to compare discussions in two sets of focus groups with relatively healthy and less healthy older adults. The thematic analysis was informed by the Transtheoretical Model, the Health Belief Model and Social Cognitive Theory.RESULTS: All participants affirmed the health benefits of physical activity and there was broad agreement that social support and conductive environments contributed to the promotion of opportunities for physical activity. However, perceptions of specific factors needed to maintain and promote good health differed between healthy and less healthy participants. Connection to community, sense of place and 'walkability' of neighbourhoods were identified as motivators for undertaking physical activity, whilst barriers were associated with health, the environment, family and attitudes to physical activity. DISCUSSIONs: The focus groups highlighted the importance of social, behavioural and contextual factors in promoting opportunities for physical activity in older adults with and without chronic illness. The findings were used to propose an Active Living Framework which is the subject of ongoing research.
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13.
  • Garcia-Rios, Antonio, et al. (författare)
  • Genetic variations at the lipoprotein lipase gene influence plasma lipid concentrations and interact with plasma n-6 polyunsaturated fatty acids to modulate lipid metabolism
  • 2011
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 218:2, s. 416-422
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate whether seven common single nucleotide polymorphisms (SNPs) at the lipoprotein lipase (LPL) locus interact with total plasma fatty acids to modulate plasma lipid metabolism in metabolic syndrome (MetS) patients. Methods: Plasma fatty acid composition, plasma lipid concentrations and LPL SNPs were determined in 452 subjects with the MetS in the European LIPGENE human study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX Study. Results: Triglycerides (TG) were lower, and HDL higher in the carriers of rs328 and rs1059611 in the SUVIMAX cohort (all P < 0.001), and these findings showed a similar, non-significant trend in LIPGENE cohort. In this last cohort, we found a gene-fatty acids interaction, as the carriers of the minor allele displayed a lower fasting TG and triglyceride rich lipoproteins-TG (TRL-TG) concentrations only when they had n-6 polyunsaturated fatty acids below the median (all P < 0.05). Moreover, subjects carrying the minor allele for rs328 SNP and with a low level of n-6 PUFA displayed higher nonesterified fatty acid (NEFA) plasma concentrations as compared with homozygous for the major allele (P = 0.034). Interestingly, the n-6 PUFA-dependent associations between those SNPs and TG metabolism were also replicated in subjects without MetS from the SU.VI.MAX cohort. Conclusion: Two genetic variations at the LPL gene (rs328 and rs1059611) influence plasma lipid concentrations and interact with plasma n-6 PUFA to modulate lipid metabolism. The knowledge of new genetic factors together with the understanding of these gene-nutrient interactions could help to a better knowledge of the pathogenesis in the MetS. 
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14.
  • Heywood, I., et al. (författare)
  • Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event
  • 2019
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 573:7773, s. 235-237
  • Tidskriftsartikel (refereegranskat)abstract
    • The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.
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15.
  • Hofherr, Alexis, et al. (författare)
  • Targeting inflammation for the treatment of Diabetic Kidney Disease: a five-compartment mechanistic model.
  • 2022
  • Ingår i: BMC nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide. Mortality and morbidity associated with DKD are increasing with the global prevalence of type 2 diabetes. Chronic, sub-clinical, non-resolving inflammation contributes to the pathophysiology of renal and cardiovascular disease associated with diabetes. Inflammatory biomarkers correlate with poor renal outcomes and mortality in patients with DKD. Targeting chronic inflammation may therefore offer a route to novel therapeutics for DKD. However, the DKD patient population is highly heterogeneous, with varying etiology, presentation and disease progression. This heterogeneity is a challenge for clinical trials of novel anti-inflammatory therapies. Here, we present a conceptual model of how chronic inflammation affects kidney function in five compartments: immune cell recruitment and activation; filtration; resorption and secretion; extracellular matrix regulation; and perfusion. We believe that the rigorous alignment of pathophysiological insights, appropriate animal models and pathology-specific biomarkers may facilitate a mechanism-based shift from recruiting 'all comers' with DKD to stratification of patients based on the principal compartments of inflammatory disease activity.
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16.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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17.
  • Hudson, Lawrence N., et al. (författare)
  • The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
  • 2014
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
  • Tidskriftsartikel (refereegranskat)abstract
    • Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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18.
  • Hummel, Kevin, et al. (författare)
  • Development of an international standard set of clinical and patient-reported outcomes for children and adults with congenital heart disease : a report from the International Consortium for Health Outcomes Measurement Congenital Heart Disease Working Group.
  • 2021
  • Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press (OUP). - 2058-5225 .- 2058-1742. ; 7:4, s. 354-365
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Congenital heart disease (CHD) is the most common congenital malformation. Despite the worldwide burden to patient wellbeing and health system resource utilization, tracking of long-term outcomes is lacking, limiting the delivery and measurement of high-value care. To begin transitioning to value-based healthcare in CHD, the International Consortium for Health Outcomes Measurement aligned an international collaborative of CHD experts, patient representatives, and other stakeholders to construct a standard set of outcomes and risk-adjustment variables that are meaningful to patients.METHODS AND RESULTS: The primary aim was to identify a minimum standard set of outcomes to be used by health systems worldwide. The methodological process included four key steps: (i) develop a working group representative of all CHD stakeholders; (ii) conduct extensive literature reviews to identify scope, outcomes of interest, tools used to measure outcomes, and case-mix adjustment variables; (iii) create the outcome set using a series of multi-round Delphi processes; and (iv) disseminate set worldwide. The Working Group established a 15-item outcome set, incorporating physical, mental, social, and overall health outcomes accompanied by tools for measurement and case-mix adjustment variables. Patients with any CHD diagnoses of all ages are included. Following an open review process, over 80% of patients and providers surveyed agreed with the set in its final form.CONCLUSION: This is the first international development of a stakeholder-informed standard set of outcomes for CHD. It can serve as a first step for a lifespan outcomes measurement approach to guide benchmarking and improvement among health systems.
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19.
  • Inabnet, William B., 3rd, et al. (författare)
  • Correlating the Bethesda System for Reporting Thyroid Cytopathology with Histology and Extent of Surgery : A Review of 21,746 Patients from Four Endocrine Surgery Registries Across Two Continents
  • 2020
  • Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 44:2, s. 426-435
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category.METHODS: Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed.RESULTS: Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31-35 years (52.1%, 95% confidence interval (CI) 37.9-66.2%), aged 36-40 years (55.9%, 95% CI 39.2-72.6%) and aged 41-45 years (46.9%, 95% CI 33-60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males.CONCLUSIONS: These data demonstrate that Bethesda categories 1-4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.
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20.
  • Jakobsdottir, Johanna, et al. (författare)
  • Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease
  • 2016
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.
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21.
  • Jallow, Muminatou, et al. (författare)
  • Genome-wide and fine-resolution association analysis of malaria in West Africa.
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; , s. 657-665
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 x 10(-7) to P = 4 x 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
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22.
  • Jones, Lesley, et al. (författare)
  • Convergent genetic and expression data implicate immunity in Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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23.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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24.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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25.
  • Kavanagh, Janine L., et al. (författare)
  • Volcanologists-who are we and where are we going?
  • 2022
  • Ingår i: Bulletin of Volcanology. - : Springer Nature. - 0258-8900 .- 1432-0819. ; 84:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Equity, diversity and inclusivity (EDI) are principles all scientific groups and organisations should strive to achieve as they secure working conditions, policies and practices that not only promote high-quality scientific output but also well-being in their communities. In this article, we reflect on the progress of EDI in volcanology by presenting data related to memberships of international volcanology organisations, positions on volcanology committees, volcanology awards and lead-authorship on volcanology papers. The sparse demographic data available means our analysis focuses mainly on gender identity discrimination, but we show that discrimination related to ethnicity, sexual orientation, religion, physical ability and socio-economic background is also occurring, with the intersection of these discriminations further exacerbating marginalisation within the volcanology community. We share suggestions and recommendations from other disciplines on how individuals, research groups and organisations can promote, develop and implement new initiatives to call out and tackle discrimination and advance EDI in the volcanological community. There is a lot of potential for improvement if we all see our role in creating a more equitable, diverse and inclusive volcanology community. This requires (1) awareness: acknowledgement of the problem, (2) commitment: through the statement of EDI core values and the development of action plans, codes of conducts and guidelines, (3) action: aiming for representation of all groups, and (4) reflection: development through critical self-reflection and a willingness to address shortcomings.
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26.
  • Kelly, Adrian B., et al. (författare)
  • Polydrug use in Australian 12-14 year olds from 2006 to 2017 : an examination of drug use profiles, emotional control problems, and family relationship characteristics
  • 2023
  • Ingår i: Australian journal of psychology. - : Taylor & Francis. - 0004-9530 .- 1742-9536. ; 75:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This study examined the nature and prevalence of polydrug use in 12–14 year old Australians.Method: Three Australian school surveys (2006, n=4091; 2009, n=5635; 2017, n=1539; age 12–14 years) spanning 11 years were used. Substances included alcohol, tobacco, cannabis, inhalant, and other illicit substances. Risk factors included depressed mood, low emotional control, poor family management and conflict, and academic performance. Latent class analysis was used to discern classes. Regression analyses were used to test the association of risk factors with classes.Results: Consistent across surveys, there was a class of adolescents who engaged in wide-ranging polydrug use, with prevalences ranging from 0.44% (2006) to 1.78% (2017). Emotional control problems, low academic performance, and poor family management were elevated in the polydrug class.Conclusion: A small proportion of 12–14-year-old adolescents engage in polydrug use. Interventions focusing on family risks and emotional control problems may be beneficial.
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27.
  • Le Guen, Yann, et al. (författare)
  • Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
  • Tidskriftsartikel (refereegranskat)abstract
    • Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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28.
  • Lessard, Christopher J., et al. (författare)
  • Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study
  • 2012
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:4, s. 648-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p(meta-Euro) = 2.08 x 10(-10)), transmembrane protein 39A (TMEM39A; rs1132200; p(meta-all) 8.62 x 10(-9)), and 17q21 (rs1453560; p(meta-all) = 3.48 x 10(-10)) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 x 10(-8) < p(meta-Euro) < 9.99 x 10(-5)) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4 FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation.
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29.
  • Luo, Jiao, et al. (författare)
  • Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease
  • 2023
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:5
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022.EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
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30.
  • Markovitz, Amanda R, et al. (författare)
  • Does pregnancy complication history improve cardiovascular disease risk prediction? : Findings from the HUNT study in Norway
  • 2019
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 40:14, s. 1113-1120
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To evaluate whether history of pregnancy complications [pre-eclampsia, gestational hypertension, preterm delivery, or small for gestational age (SGA)] improves risk prediction for cardiovascular disease (CVD).Methods and results: This population-based, prospective cohort study linked data from the HUNT Study, Medical Birth Registry of Norway, validated hospital records, and Norwegian Cause of Death Registry. Using an established CVD risk prediction model (NORRISK 2), we predicted 10-year risk of CVD (non-fatal myocardial infarction, fatal coronary heart disease, and non-fatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and HDL-cholesterol, smoking, anti-hypertensives, and family history of myocardial infarction). We evaluated whether adding pregnancy complication history improved model fit, calibration, discrimination, and reclassification. Among 18 231 women who were parous, ≥40 years of age, and CVD-free at start of follow-up, 39% had any pregnancy complication history and 5% experienced a CVD event during a median follow-up of 8.2 years. While pre-eclampsia and SGA were associated with CVD in unadjusted models (HR 1.96, 95% CI 1.44-2.65 for pre-eclampsia and HR 1.46, 95% CI 1.18-1.81 for SGA), only pre-eclampsia remained associated with CVD after adjusting for established risk factors (HR 1.60, 95% CI 1.16-2.17). Adding pregnancy complication history to the established prediction model led to small improvements in discrimination (C-index difference 0.004, 95% CI 0.002-0.006) and reclassification (net reclassification improvement 0.02, 95% CI 0.002-0.05).Conclusion: Pre-eclampsia independently predicted CVD after controlling for established risk factors; however, adding pre-eclampsia, gestational hypertension, preterm delivery, and SGA made only small improvements to CVD prediction among this representative sample of parous Norwegian women.
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31.
  • McCallum, Fiona J., et al. (författare)
  • Differing rates of antibody acquisition to merozoite antigens in malaria : Implications for immunity and surveillance
  • 2017
  • Ingår i: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 101:4, s. 913-925
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibodies play a key role in acquired human immunity to Plasmodium falciparum (Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity. We examined responses to a range of merozoite antigens in 2 different cohorts of children and adults with different age structures and levels of malaria exposure. Overall, antibodies were associated with age, exposure, and active infection, and the repertoire of responses increased with age and active infection. However, rates of antibody acquisition varied between antigens and different regions within an antigen following exposure to malaria, supporting our hypothesis. Antigen-specific responses could be broadly classified into early response types in which antibodies were acquired early in childhood exposure and late response types that appear to require substantially more exposure for the development of substantial levels. We identified antigen-specific responses that were effectively boosted after recent infection, whereas other responses were not. These findings advance our understanding of the acquisition of human immunity to malaria and are relevant to the development of malaria vaccines targeting merozoite antigens and the selection of antigens for use in malaria surveillance.
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32.
  • Mychaleckyj, Josyf C., et al. (författare)
  • HLA genotyping in the international Type 1 Diabetes Genetics Consortium
  • 2010
  • Ingår i: Clinical Trials. - : SAGE Publications. - 1740-7753 .- 1740-7745. ; 7:1 suppl., s. 75-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers. Purpose In this article, we present the operational strategy of training, classification, reporting, and quality control of HLA genotyping in four laboratories on three continents over nearly 5 years. Methods Methods to standardize HLA genotyping at eight loci included: central training and initial certification testing; the use of uniform reagents, protocols, instrumentation, and software versions; an automated data transfer; and the use of standardized nomenclature and allele databases. We implemented a rigorous and consistent quality control process, reinforced by repeated workshops, yearly meetings, and telephone conferences. Results A total of 15,246 samples have been HLA genotyped at eight loci to four-digit resolution; an additional 6797 samples have been HLA genotyped at two loci. The genotyping repeat rate decreased significantly over time, with an estimated unresolved Mendelian inconsistency rate of 0.21%. Annual quality control exercises tested 2192 genotypes (4384 alleles) and achieved 99.82% intra-laboratory and 99.68% inter-laboratory concordances. Limitations The chosen genotyping platform was unable to distinguish many allele combinations, which would require further multiple stepwise testing to resolve. For these combinations, a standard allele assignment was agreed upon, allowing further analysis if required. Conclusions High-resolution HLA genotyping can be performed in multiple laboratories using standard equipment, reagents, protocols, software, and communication to produce consistent and reproducible data with minimal systematic error. Many of the strategies used in this study are generally applicable to other large multi-center studies. Clinical Trials 2010; 7: S75-S87. http://ctj.sagepub.com.
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33.
  • Navin Cristina, Tina J, et al. (författare)
  • Identification of diabetes, heart disease, hypertension and stroke in mid- and older-aged women : Comparing self-report and administrative hospital data records
  • 2016
  • Ingår i: Geriatrics & Gerontology International. - : Wiley. - 1444-1586 .- 1447-0594. ; 16:1, s. 95-102
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To estimate the prevalence of diabetes, heart disease, hypertension and stroke in self-report and hospital data in two cohorts of women; measure sensitivity and agreement between data sources; and compare between cohorts.METHODS: Women born between 1946-1951 and 1921-1926 who participated in the Australian Longitudinal Study on Women's Health (ALSWH); were New South Wales residents; and admitted to hospital (2004-2008) were included in the present study. The prevalence of diabetes, heart disease, hypertension and stroke was estimated using self-report (case 1 at latest survey, case 2 across multiple surveys) and hospital records. Agreement (kappa) and sensitivity (%) were calculated. Logistic regression measured the association between patient characteristics and agreement.RESULTS: Hypertension had the highest prevalence and estimates were higher for older women: 32.5% case 1, 45.4% case 2, 12.8% in hospital data (1946-1951 cohort); 57.8% case 1, 73.2% case 2, 38.2% in hospital data (1921-1926 cohort). Agreement was substantial for diabetes: κ = 0.75 case 1, κ = 0.70 case 2 (1946-1951 cohort); κ = 0.77 case 1, κ = 0.80 case 2 (1921-1926 cohort), and lower for other conditions. The 1946-1951 cohort had 2.08 times the odds of agreement for hypertension (95% CI 1.56 to 2.78; P < 0.0001), and 6.25 times the odds of agreement for heart disease (95% CI 4.35 to 10.0; P < 0.0001), compared with the 1921-1926 cohort.CONCLUSION: Substantial agreement was found for diabetes, indicating accuracy of ascertainment using self-report or hospital data. Self-report data appears to be less accurate for heart disease and stroke. Hypertension was underestimated in hospital data. These findings have implications for epidemiological studies relying on self-report or administrative data. Geriatr Gerontol Int 2015
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34.
  • O'Neil, Adrienne, et al. (författare)
  • The impact of statins on psychological wellbeing: a systematic review and meta-analysis
  • 2012
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 10
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Cholesterol-lowering medications such as statins have anti-inflammatory and antioxidant properties, which may be beneficial for treating depression and improving mood. However, evidence regarding their effects remains inconsistent, with some studies reporting links to mood disturbances. We aimed to conduct a meta-analysis to determine the impact of statins on psychological wellbeing of individuals with or without hypercholesterolemia. Methods: Articles were identified using medical, health, psychiatric and social science databases, evaluated for quality, and data were synthesized and analyzed in RevMan-5 software using a random effects model. Results: The 7 randomized controlled trials included in the analysis represented 2,105 participants. A test for overall effect demonstrated no statistically significant differences in psychological wellbeing between participants receiving statins or a placebo (standardized mean difference (SMD) = -0.08, 95% CI -0.29 to 0.12; P = 0.42). Sensitivity analyses were conducted to separately analyze depression (n = 5) and mood (n = 2) outcomes; statins were associated with statistically significant improvements in mood scores (SMD = -0.43, 95% CI -0.61 to -0.24). Conclusions: Our findings refute evidence of negative effects of statins on psychological outcomes, providing some support for mood-related benefits. Future studies could examine the effects of statins in depressed populations.
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35.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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36.
  • Parkinson, Lynne, et al. (författare)
  • An observational study of the discrediting of COX-2 NSAIDs in Australia : Vioxx or class effect?
  • 2011
  • Ingår i: BMC Public Health. - : Springer. - 1471-2458. ; 11, s. 892-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: When a medicine such as rofecoxib (Vioxx) is withdrawn, or a whole class of medicines discredited such as the selective COX-2 inhibitors (COX-2s), follow-up of impacts at consumer level can be difficult and costly. The Australian Longitudinal Study on Women's Health provides a rare opportunity to examine individual consumer medicine use following a major discrediting event, the withdrawal of rofecoxib and issuing of safety warnings on the COX-2 class of medicines. The overall objective of this paper was to examine the impact of this discrediting event on dispensing of the COX-2 class of medicines, by describing medicine switching behaviours of older Australian women using rofecoxib in September 2004; the uptake of other COX-2s; and the characteristics of women who continued using a COX-2.METHODS: Participants were concessional beneficiary status women from the Older cohort (born 1921-26) of the Australian Longitudinal Study on Women's Health who consented to linkage to Pharmaceutical Benefits Scheme data, with at least one rofecoxib prescription dispensed in the 12 months before rofecoxib withdrawal. A prescription was defined as one dispensing occasion. Women were grouped by rofecoxib pattern of use: continuous (nine or more prescriptions dispensed in the 12 months prior to rofecoxib withdrawal) or non-continuous (eight or less prescriptions dispensed in the 12 months prior to rofecoxib withdrawal) users. Incidence rate per 100,000 person days and incidence risk ratio described uptake of alternate medicines, following rofecoxib withdrawal. Kaplan-Meier curves described differences in uptake patterns by medicine and pattern of rofecoxib use. Patterns of use of COX-2s in the next 100 days after first COX-2 uptake were described.RESULTS: Medicine switches and pattern of medicines uptake differed significantly depending upon whether a woman was a continuous or non-continuous rofecoxib user prior to rofecoxib discrediting. Continuous rofecoxib users overwhelmingly switched to another COX-2 and remained continuing COX-2 users for at least 100 days post-switch.CONCLUSIONS: The typical switching behaviour of this group of women suggests that the issues leading to the discrediting of rofecoxib were not seen as a COX-2 class effect by prescribers to this high use group of consumers.
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37.
  • Perez-Martinez, Pablo, et al. (författare)
  • Calpain-10 interacts with plasma saturated fatty acid concentrations to influence insulin resistance in individuals with the metabolic syndrome
  • 2011
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 93:5, s. 1136-1141
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Calpain-10 protein (intracellular Ca2+-dependent cysteine protease) may play a role in glucose metabolism, pancreatic beta cell function, and regulation of thermogenesis. Several CAPN10 polymorphic sites have been studied for their potential use as risk markers for type 2 diabetes and the metabolic syndrome (MetS). Fatty acids are key metabolic regulators that may interact with genetic factors and influence glucose metabolism. Objective: The objective was to examine whether the genetic variability at the CAPN10 gene locus is associated with the degree of insulin resistance and plasma fatty acid concentrations in subjects with MetS. Design: The insulin sensitivity index, glucose effectiveness, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], insulin secretion (disposition index, acute insulin response, and HOMA of beta cell function), plasma fatty acid composition, and 5 CAPN10 single nucleotide polymorphisms (SNPs) were determined in a cross-sectional analysis of 452 subjects with MetS participating in the LIPGENE dietary intervention cohort. Results: The rs2953171 SNP interacted with plasma total saturated fatty acid (SFA) concentrations, which were significantly associated with insulin sensitivity (P < 0.031 for fasting insulin, P < 0.028 for HOMA-IR, and P < 0.012 for glucose effectiveness). The G/G genotype was associated with lower fasting insulin concentrations, lower HOMA-IR, and higher glucose effectiveness in subjects with low SFA concentrations (below the median) than in subjects with the minor A allele (G/A and A/A). In contrast, subjects with the G/G allele with the highest SFA concentrations (above the median) had higher fasting insulin and HOMA-IR values and lower glucose effectiveness than did subjects with the A allele. Conclusion: The rs2953171 polymorphism at the CAPN10 gene locus may influence insulin sensitivity by interacting with the plasma fatty acid composition in subjects with MetS. This trial was registered at clinicaltrials. gov as NCT00429195.
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38.
  • Perez-Martinez, Pablo, et al. (författare)
  • Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome : Association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance
  • 2012
  • Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 56:2, s. 309-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Scope: Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects.Methods and results: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p < 0.038), higher fasting insulin concentrations (p < 0.028) and higher HOMA IR (p < 0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of omega-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p < 0.01) and HOMA-IR (p < 0.02) as compared with A/A subjects.Conclusion: The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects.
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39.
  • Salinas, Joel, et al. (författare)
  • An International Standard Set of Patient-Centered Outcome Measures After Stroke.
  • 2016
  • Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 47:1, s. 180-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Value-based health care aims to bring together patients and health systems to maximize the ratio of quality over cost. To enable assessment of healthcare value in stroke management, an international standard set of patient-centered stroke outcome measures was defined for use in a variety of healthcare settings.
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40.
  • Stevenson-Hoare, Joshua, et al. (författare)
  • Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease.
  • 2023
  • Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 146:2, s. 690-699
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma biomarkers for Alzheimer's disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation. To define Alzheimer's disease with biomarkers rather than clinical assessment, we assessed prediction of research-diagnosed disease status using these biomarkers and tested genetic variants associated with the biomarkers that may reflect more accurately the risk of biochemically defined Alzheimer's disease instead of the risk of dementia. In a cohort of Alzheimer's disease cases (N=1439, mean age 68 years [SD=8.2]) and screened controls (N=508, mean age 82 years [SD=6.8]), we measured plasma concentrations of the 40 and 42 amino acid-long amyloid β fragments (Aβ40 and Aβ42, respectively), tau phosphorylated at amino acid 181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) using state-of-the-art Single molecule array (Simoa) technology. We tested the relationships between the biomarkers and Alzheimer's disease genetic risk, age at onset, and disease duration. We also conducted a genome-wide association study for association of disease risk genes with these biomarkers. The prediction accuracy of Alzheimer's disease clinical diagnosis by the combination of all biomarkers, APOE and polygenic risk score reached AUC=0.81, with the most significant contributors being ε4, Aβ40 or Aβ42, GFAP and NfL. All biomarkers were significantly associated with age in cases and controls (p<4.3x10-5). Concentrations of the Aβ-related biomarkers in plasma were significantly lower in cases compared with controls, whereas other biomarker levels were significantly higher in cases. In the case-control genome-wide analyses, APOE-ε4 was associated with all biomarkers (p=0.011- 4.78x10-8), except NfL. No novel genome-wide significant SNPs were found in the case-control design; however, in a case-only analysis, we found two independent genome-wide significant associations between the Aβ42/Aβ40 ratio and WWOX and COPG2 genes. Disease prediction modelling by the combination of all biomarkers indicates that the variance attributed to P-tau181 is mostly captured by APOE-ε4, whereas Aβ40, Aβ42, GFAP and NfL biomarkers explain additional variation over and above APOE. We identified novel plausible genome wide-significant genes associated with Aβ42/Aβ40 ratio in a sample which is fifty times smaller than current genome-wide association studies in Alzheimer's disease.
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41.
  • Stewart Williams, Jennifer A, et al. (författare)
  • Assessing patterns of use of cardio-protective polypill component medicines in Australian women
  • 2013
  • Ingår i: Drugs & Aging. - : Springer. - 1170-229X .- 1179-1969. ; 30:3, s. 193-203
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A low-cost 'polypill' could theoretically be one way of improving medication affordability and compliance for secondary prevention of cardiovascular and cerebrovascular disease. The polypill has also been proposed as a primary prevention strategy. Yet many of the issues surrounding the polypill are still being debated and the underlying assumptions have not been proven. In this paper, we step back from the complexities of the debate and report upon the utilization of polypill component medicines in two population cohorts of Australian women who were aged 56-61 years and 81-86 years in 2007.OBJECTIVES: The aims of this study were firstly, to describe the association between the women's characteristics (health, illness, behavioural, demographic, socioeconomic) and their use of statins and antihypertensive medicines for the treatment of heart disease, and secondly, to discuss possible health and economic benefits for women with these characteristics that may be expected to result from the introduction of a cardio-protective polypill.METHODS: Survey records from the Australian Longitudinal Study on Women's Health (ALSWH) were linked to 2007 Pharmaceutical Benefits Scheme (PBS) claims for 7,116 mid-aged women and 4,526 older-aged women. Associations between women's characteristics (self-reported in ALSWH surveys) and their use of statins and antihypertensive medicines (measured through PBS claims in 2007) were analysed using Chi-square and multivariate regression techniques.RESULTS: Between 2002 and 2007, the use of statins in combination with antihypertensives by mid- and older-aged Australian women increased. A moderate yet increasing proportion of mid-aged women were taking statins without antihypertensives, and a high proportion of older-aged women were using antihypertensives without statins. A high proportion of women who were prescribed both statins and antihypertensives were in lower socioeconomic groups and reported difficulty managing on their incomes.CONCLUSION: These results suggest that a polypill may provide an easy-to-take, cheaper alternative for Australian women already taking multiple cardiovascular disease medications, with particular benefits for older women and women in lower socioeconomic groups. Future research is needed to quantify the potential social and economic benefits of the polypill.
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42.
  • Stewart Williams, Jennifer, et al. (författare)
  • Identification of higher hospital costs and more frequent admissions among mid-aged Australian women who self-report diabetes mellitus
  • 2016
  • Ingår i: Maturitas. - : Elsevier. - 0378-5122 .- 1873-4111. ; 90, s. 58-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To ascertain whether the hospital costs for mid-aged Australian women who self-reported diabetes mellitus (DM) and who had one or more hospital admission during an eight and a half year period were higher than the hospital costs for other similarly aged non-DM women. Methods: The sample comprised 2,392 mid-aged women, resident in New South Wales (NSW) Australia and participating in the Australian Longitudinal Study on Women’s Health (ALSWH), who had any NSW hospital admissions during the eight and a half year period 1 July 2000 to 31 December 2008. Analyses were conducted on linked data from ALSWH surveys and the NSW Admitted Patient Data Collection (APDC). Hospital costs were compared for the DM and non-DM cohorts of women. A generalized linear model measured the association between hospital costs and self-reported DM. Results: Eight and a half year hospital costs were 41% higher for women who self-reported DM in the ALSWH surveys (p < 0.0001). On average, women who self-reported DM had significantly (p < 0.0001) more hospital admissions (5.3) than women with no reported DM (3.4). The average hospital stay per admission was not significantly different between the two groups of women. Conclusions: Self-reported DM status in mid-aged Australian women is a predictor of higher hospital costs. This simple measure can be a useful indicator for public policy makers planning early-stage interventions that target people in the population at risk of DM.
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43.
  • Stewart Williams, Jennifer, et al. (författare)
  • The impact of socioeconomic status on changes in the general and mental health of women over time : evidence from a longitudinal study of Australian women
  • 2013
  • Ingår i: International Journal for Equity in Health. - : Springer Science and Business Media LLC. - 1475-9276. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Generally, men and women of higher socioeconomic status (SES) have better health. Little is known about how socioeconomic factors are associated with changes in health as women progress through mid-life. This study uses data from six survey waves (1996 to 2010) of the Australian Longitudinal Study on Women's Health (ALSWH) to examine associations between SES and changes in the general health and mental health of a cohort of women progressing in years from 45-50 to 59-64.METHODS: Participants were 12,709 women (born 1946-51) in the ALSWH. Outcome measures were the general health and mental health subscales of the Medical Outcomes Study Short Form 36 Questionnaire (SF-36). The measure of SES was derived from factor analysis of responses to questions in the ALSWH baseline survey (1996) on school leaving age, highest qualifications, and current or last occupation. Multi-level random coefficient models, adjusted for socio-demographic factors and health behaviors, were used to analyze repeated measures of general health and mental health. Survey year accounted for changes in factors across time. In the first set of analyses we investigated associations between the SES index, used as a "continuous" variable, and general health and mental health changes over time. To illuminate the impact of different levels of SES on health, a second analysis was conducted in which SES scores were grouped into three approximately equal sized categories or "tertiles" as reported in an earlier ALSWH study. The least square means of general and mental health scores from the longitudinal models were plotted for the three SES tertiles.RESULTS: The longitudinal analysis showed that, after adjusting for the effects of time and possible confounders, the general (mental) health of this cohort of mid-aged women declined (increased) over time. Higher SES women reported better health than lower SES women, and SES significantly modified the effects of time on both general and mental health in favor of higher SES women.CONCLUSIONS: This study contributes to our current understanding of how socioeconomic and demographic factors, health behaviors and time impact on changes in the general and mental health of women progressing in years from 45-50 to 59-64.
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44.
  • Welsh, Joshua A., et al. (författare)
  • Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
  • 2024
  • Ingår i: Journal of Extracellular Vesicles. - : John Wiley and Sons Inc. - 2001-3078. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
  •  
45.
  • Williams, C. M., et al. (författare)
  • Pelagic microbial heterotrophy in response to a highly productive bloom of Phaeocystis antarctica in the Amundsen Sea Polynya, Antarctica
  • 2016
  • Ingår i: Elementa. - : University of California Press. - 2325-1026. ; 4, s. 1-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Heterotrophic bacteria play a key role in marine carbon cycling, and understanding their activities in polar systems is important for considering climate change impacts there. One goal of the ASPIRE project was to examine the relationship between the phytoplankton bloom and bacterial heterotrophy in the Amundsen Sea Polynya (ASP). Bacterial abundance, production (BP), respiration, growth efficiency, and extracellular enzyme activity (EEA) were compared to nutrient and organic matter inventories, chlorophyll a (Chl a), viral and microzooplankton abundance, and net primary production (NPP). Bacterial production and respiration clearly responded (0.04-4.0 and 10-53 mu g C L-1 d(-1), respectively) to the buildup of a massive Phaeocystis antarctica bloom (Chl a: 0.2-22 mu g L-1), with highest rates observed in the central polynya where Chl a and particulate organic carbon (POC) were greatest. The highest BP rates exceeded those reported for the Ross Sea or any other Antarctic coastal system, yet the BP: NPP ratio (2.1-9.4%) was relatively low. Bacterial respiration was also high, and growth efficiency (2-27%; median = 10%) was similar to oligotrophic systems. Thus, the integrated bacterial carbon demand (0.8-2.8 g C m(-2) d(-1)) was a high fraction (25-128%; median = 43%) of NPP during bloom development. During peak bloom, activity was particle-associated: BP and EEA correlated well with POC, and size fractionation experiments showed that the larger size fraction (> 3 mu m) accounted for a majority (similar to 75%) of the BP. The community was psychrophilic, with a 5x reduction in BP when warmed to 20 degrees C. In deeper waters, respiration remained relatively high, likely fueled by the significant downward particle flux in the region. A highly active, particle-associated, heterotrophic microbial community clearly responded to the extraordinary phytoplankton bloom in the ASP, likely limiting biological pump efficiency during the early season.
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46.
  • Williams, David J., et al. (författare)
  • Comparability : Manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14-15 September 2015
  • 2016
  • Ingår i: Regenerative Medicine. - : Future Medicine Ltd. - 1746-0751 .- 1746-076X. ; 11:5, s. 483-492
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates.
  •  
47.
  • Williams, Jennifer A Stewart, et al. (författare)
  • Equity of access to cardiac rehabilitation : the role of system factors.
  • 2010
  • Ingår i: International journal for equity in health. - : Springer Science and Business Media LLC. - 1475-9276. ; 9, s. 2-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: When patient selection processes determine who can and cannot use healthcare there can be inequalities and inequities in individuals' opportunities to benefit. This paper evaluates the influence of a hospital selection process on opportunities to access outpatient cardiac rehabilitation (CR).METHODS: A secondary data analysis was conducted on a cohort of inpatients (n = 2,375) who were all eligible for invitation to an Australian CR program. Eligibility was determined by hospital discharge diagnosis codes. Only invited patients could attend. Logistic regression analysis tested the extent to which individual patient characteristics were statistically significantly associated with the outcome 'invitation' after adjusting for cardiac disease and other factors.RESULTS: Less than half of the eligible patients were invited to the CR program. After allowing for known factors that may have justified not being selected, there was bias towards inviting males, younger patients, married patients, and patients who nominated English as their preferred language.CONCLUSIONS: Health service managers typically monitor service utilisation patterns as indicators of access but often pay little attention to ways in which locally determined system factors influence access to care. The paper shows how a hospital selection process can unreasonably influence patients' opportunities to benefit from an evidence-based healthcare program.
  •  
48.
  • Yager, P. L., et al. (författare)
  • A carbon budget for the Amundsen Sea Polynya, Antarctica: Estimating net community production and export in a highly productive polar ecosystem
  • 2016
  • Ingår i: Elementa-Science of the Anthropocene. - : University of California Press. - 2325-1026. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Polynyas, or recurring areas of seasonally open water surrounded by sea ice, are foci for energy and material transfer between the atmosphere and the polar ocean. They are also climate sensitive, with both sea ice extent and glacial melt influencing their productivity. The Amundsen Sea Polynya (ASP) is the greenest polynya in the Southern Ocean, with summertime chlorophyll a concentrations exceeding 20 mu g L-1. During the Amundsen Sea Polynya International Research Expedition (ASPIRE) in austral summer 2010-11, we aimed to determine the fate of this high algal productivity. We collected water column profiles for total dissolved inorganic carbon (DIC) and nutrients, particulate and dissolved organic matter, chlorophyll a, mesozoo-plankton, and microbial biomass to make a carbon budget for this ecosystem. We also measured primary and secondary production, community respiration rates, vertical particle flux and fecal pellet production and grazing. With observations arranged along a gradient of increasing integrated dissolved inorganic nitrogen drawdown (Delta DIN; 0.027-0.74 mol N m(-2)), changes in DIC in the upper water column (ranging from 0.2 to 4.7 mol C m(-2)) and gas exchange (0-1.7 mol C m(-2)) were combined to estimate early season net community production (sNCP; 0.2-5.9 mol C m(-2)) and then compared to organic matter inventories to estimate export. From a phytoplankton bloom dominated by Phaeocystis antarctica, a high fraction (up to similar to 60%) of sNCP was exported to sub-euphotic depths. Microbial respiration remineralized much of this export in the mid waters. Comparisons to short-term (2-3 days) drifting traps and a year-long moored sediment trap capturing the downward flux confirmed that a relatively high fraction (3-6%) of the export from similar to 100 m made it through the mid waters to depth. We discuss the climate-sensitive nature of these carbon fluxes, in light of the changing sea ice cover and melting ice sheets in the region.
  •  
49.
  • Yego, Faith, et al. (författare)
  • A retrospective analysis of maternal and neonatal mortality at a teaching and referral hospital in Kenya
  • 2013
  • Ingår i: Reproductive Health. - : Springer. - 1742-4755. ; 10, s. 13-
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To measure the incidence of maternal and early neonatal mortality in women who gave birth at Moi Teaching and Referral Hospital (MTRH) in Kenya and describe clinical and other characteristics and circumstances associated with maternal and neonatal deaths following deliveries at MTRH.METHODS: A retrospective audit of maternal and neonatal records was conducted with detailed analysis of the most recent 150 maternal deaths and 200 neonatal deaths. Maternal mortality ratios and early neonatal mortality rates were calculated for each year from January 2004 to December 2011.RESULTS: Between 2004 and 2011, the overall maternal mortality ratio was 426 per 100,000 live births and the early neonatal mortality rate (<7 days) was 68 per 1000 live births. The Hospital record audit showed that half (51%) of the neonatal mortalities were for young mothers (15-24 years) and 64% of maternal deaths were in women between 25 and 45 years. Most maternal and early neonatal deaths occurred in multiparous women, in referred admissions, when the gestational age was under 37 weeks and in latent stage of labour. Indirect complications accounted for the majority of deaths. Where there were direct obstetric complications associated with the delivery, the leading cause of maternal death was eclampsia and the leading cause of early neonatal death was pre-mature rupture of membranes. Pre-term birth and asphyxia were leading causes of early neonatal deaths. In both sets of records the majority of deliveries were vaginal and performed by midwives.CONCLUSION: This study provides important information about maternal and early neonatal mortality in Kenya's second largest tertiary hospital. A range of socio demographic, clinical and health system factors are identified as possible contributors to Kenya's poor progress towards reducing maternal and early neonatal mortality.
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50.
  • Yego, Faith H, et al. (författare)
  • A case-control study of risk factors for fetal and early neonatal deaths in a tertiary hospital in Kenya
  • 2014
  • Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 14, s. 389-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIt is important to understand the risk factors for fetal and neonatal mortality which is a major contributor to high under five deaths globally. Fetal and neonatal mortality is a sensitive indicator of maternal health in society. This study aimed to examine the risk factors for fetal and early neonatal mortality at the Moi Teaching and Referral Hospital in Kenya.MethodsThis was a case-control study. Cases were fetal and early neonatal deaths (n¿=¿200). The controls were infants born alive immediately preceding and following the cases (n¿=¿400). Bivariate comparisons and multiple logistic regression analyses were undertaken.ResultsThe odds of having 0-1 antenatal visits relative to 2-3 visits were higher for cases than controls (AOR=4.5; 95% CI: 1.2-16.7; p=0.03). There were lower odds among cases of having a doctor rather than a midwife as a birth attendant (OR¿=¿0.2; 95% CI: 0.1-0.6; p¿<¿0.01). The odds of mothers having Premature Rupture of Membranes (OR¿=¿4.1; 95% CI: 1.4-12.1; p¿=¿0.01), haemorrhage (OR¿=¿4.8; 95% CI: 1.1-21.9; p¿=¿0.04) and dystocia (OR¿=¿3.6; 95% CI: 1.2-10.9; p¿=¿0.02) were higher for the cases compared with the controls. The odds of gestational age less than 37 weeks (OR¿=¿7.0; 95% CI 2.4-20.4) and above 42 weeks (OR¿=¿16.2; 95% CI 2.8-92.3) compared to 37-42 weeks, were higher for cases relative to controls (p¿<¿0.01). Cases had higher odds of being born with congenital malformations (OR¿=¿6.3; 95% CI: 1.2-31.6; p¿=¿0.04) and with Apgar scores of below six at five minutes (OR¿=¿26.4; 95% CI: 6.1-113.8; p¿<¿0.001).ConclusionInterventions that focus on educating mothers on antenatal attendance, screening, monitoring and management of maternal conditions during the antenatal period should be strengthened. Doctor attendance at each birth and for emergency admissions is important to ensure early neonatal survival and avert potential risk factors for mortality.
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