| 1. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 2. |
- Downey, Harriet, et al.
(författare)
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Training future generations to deliver evidence-based conservation and ecosystem management
- 2021
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Ingår i: Ecological Solutions and Evidence. - : Wiley. - 2688-8319. ; 2:1
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Forskningsöversikt (refereegranskat)abstract
- 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis.2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice.3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses.4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.
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| 3. |
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| 4. |
- Butler, P. A., et al.
(författare)
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The observation of vibrating pear-shapes in radon nuclei
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.
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| 5. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 6. |
- Butler, P. A., et al.
(författare)
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Evolution of Octupole Deformation in Radium Nuclei from Coulomb Excitation of Radioactive ^{222}Ra and ^{228}Ra Beams
- 2020
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Ingår i: Physical Review Letters. - 1079-7114. ; 124:4
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Tidskriftsartikel (refereegranskat)abstract
- There is sparse direct experimental evidence that atomic nuclei can exhibit stable "pear" shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole (E3) matrix elements have been determined for transitions in ^{222,228}Ra nuclei using the method of sub-barrier, multistep Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of E3 matrix elements for different nuclear transitions is explained by describing ^{222}Ra as pear shaped with stable octupole deformation, while ^{228}Ra behaves like an octupole vibrator.
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| 7. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 8. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 9. |
- Spagnoletti, P., et al.
(författare)
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Coulomb excitation of Rn 222
- 2022
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Ingår i: Physical Review C. - 2469-9985. ; 105:2
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Tidskriftsartikel (refereegranskat)abstract
- The nature of quadrupole and octupole collectivity in Rn222 was investigated by determining the electric-quadrupole (E2) and octupole (E3) matrix elements using subbarrier, multistep Coulomb excitation. The radioactive Rn222 beam, accelerated to 4.23 MeV/u, was provided by the HIE-ISOLDE facility at CERN. Data were collected in the Miniball γ-ray spectrometer following the bombardment of two targets, Sn120 and Ni60. Transition E2 matrix elements within the ground-state and octupole bands were measured up to 10ℏ and the results were consistent with a constant intrinsic electric-quadrupole moment, 518(11)efm2. The values of the intrinsic electric-octupole moment for the 0+→3- and 2+→5- transitions were found to be respectively 2360-210+300efm3 and 2300-500+300efm3 while a smaller value, 1200-900+500efm3, was found for the 2+→1- transition. In addition, four excited non-yrast states were identified in this work via γ-γ coincidences.
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| 10. |
- Devries, K., et al.
(författare)
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Who perpetrates violence against children? A systematic analysis of age-specific and sex-specific data
- 2018
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Ingår i: BMJ Paediatr Open. - : BMJ. - 2399-9772. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The epidemiology of violence against children is likely to differ substantially by sex and age of the victim and the perpetrator. Thus far, investment in effective prevention strategies has been hindered by lack of clarity in the burden of childhood violence across these dimensions. We produced the first age-specific and sex-specific prevalence estimates by perpetrator type for physical, sexual and emotional violence against children globally. Design: We used random effects meta-regression to estimate prevalence. Estimates were adjusted for relevant quality covariates, variation in definitions of violence and weighted by region-specific, age-specific and sex-specific population data to ensure estimates reflect country population structures. Data sources: Secondary data from 600 population or school-based representative datasets and 43 publications obtained via systematic literature review, representing 13 830 estimates from 171 countries. Eligibility criteria for selecting studies: Estimates for recent violence against children aged 0-19 were included. Results: The most common perpetrators of physical and emotional violence for both boys and girls across a range of ages are household members, with prevalence often surpassing 50%, followed by student peers. Children reported experiencing more emotional than physical violence from both household members and students. The most common perpetrators of sexual violence against girls aged 15-19 years are intimate partners; however, few data on other perpetrators of sexual violence against children are systematically collected internationally. Few age-specific and sex-specific data are available on violence perpetration by schoolteachers; however, existing data indicate high prevalence of physical violence from teachers towards students. Data from other authority figures, strangers, siblings and other adults are limited, as are data on neglect of children. Conclusions: Without further investment in data generation on violence exposure from multiple perpetrators for boys and girls of all ages, progress towards Sustainable Development Goals 4, 5 and 16 may be slow. Despite data gaps, evidence shows violence from household members, peers in school and for girls, from intimate partners, should be prioritised for prevention. Trial registration number: PROSPERO 2015: CRD42015024315.
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| 11. |
- Wade, Alisha N., et al.
(författare)
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Concordance between fasting plasma glucose and HbA1c in the diagnosis of diabetes in black South African adults: A cross-sectional study
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We investigated concordance between haemoglobin A1c (HbA1c)-defined diabetes and fasting plasma glucose (FPG)-defined diabetes in a black South African population with a high prevalence of obesity.Design: Cross-sectional study.Setting: Rural South African population-based cohort.Participants: 765 black individuals aged 40–70 years and with no history of diabetes.Primary and secondary outcome measures: The primary outcome measure was concordance between HbA1c-defined diabetes and FPG-defined diabetes. Secondary outcome measures were differences in anthropometric characteristics, fat distribution and insulin resistance (measured using Homoeostatic Model Assessment of Insulin Resistance (HOMA-IR)) between those with concordant and discordant HbA1c/FPG classifications and predictors of HbA1c variance.Results: The prevalence of HbA1c-defined diabetes was four times the prevalence of FPG-defined diabetes (17.5% vs 4.2%). Classification was discordant in 15.7% of participants, with 111 individuals (14.5%) having HbA1c-only diabetes (kappa 0.23; 95% CI 0.14 to 0.31). Median body mass index, waist and hip circumference, waist-to-hip ratio, subcutaneous adipose tissue and HOMA-IR in participants with HbA1c-only diabetes were similar to those in participants who were normoglycaemic by both biomarkers and significantly lower than in participants with diabetes by both biomarkers (p<0.05). HOMA-IR and fat distribution explained additional HbA1c variance beyond glucose and age only in women.Conclusions: Concordance was poor between HbA1c and FPG in diagnosis of diabetes in black South Africans, and participants with HbA1c-only diabetes phenotypically resembled normoglycaemic participants. Further work is necessary to determine which of these parameters better predicts diabetes-related morbidities in this population and whether a population-specific HbA1c threshold is necessary.
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| 12. |
- Buffart, L. M., et al.
(författare)
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Effects and moderators of coping skills training on symptoms of depression and anxiety in patients with cancer : Aggregate data and individual patient data meta-analyses
- 2020
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Ingår i: Clinical Psychology Review. - : Elsevier BV. - 0272-7358 .- 1873-7811. ; 80
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: This study evaluated the effects of coping skills training (CST) on symptoms of depression and anxiety in cancer patients, and investigated moderators of the effects.METHODS: Overall effects and intervention-related moderators were studied in meta-analyses of pooled aggregate data from 38 randomized controlled trials (RCTs). Patient-related moderators were examined using linear mixed-effect models with interaction tests on pooled individual patient data (n = 1953) from 15 of the RCTs.RESULTS: CST had a statistically significant but small effect on depression (g = -0.31,95% confidence interval (CI) = -0.40;-0.22) and anxiety (g = -0.32,95%CI = -0.41;-0.24) symptoms. Effects on depression symptoms were significantly larger for interventions delivered face-to-face (p = .003), led by a psychologist (p = .02) and targeted to patients with psychological distress (p = .002). Significantly larger reductions in anxiety symptoms were found in younger patients (pinteraction < 0.025), with the largest reductions in patients <50 years (β = -0.31,95%CI = -0.44;-0.18) and no significant effects in patients ≥70 years. Effects of CST on depression (β = -0.16,95%CI = -0.25;-0.07) and anxiety (β = -0.24,95%CI = -0.33;-0.14) symptoms were significant in patients who received chemotherapy but not in patients who did not (pinteraction < 0.05).CONCLUSIONS: CST significantly reduced symptoms of depression and anxiety in cancer patients, and particularly when delivered face-to-face, provided by a psychologist, targeted to patients with psychological distress, and given to patients who were younger and received chemotherapy.
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| 13. |
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| 14. |
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| 15. |
- Lu, J., et al.
(författare)
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Structural, Spectroscopic, and Electrochemical Characterization of Semi-Conducting, Solvated [Pt(NH 3 ) 4 ](TCNQ) 2 ·(DMF) 2 and Non-Solvated [Pt(NH 3 ) 4 ](TCNQ) 2
- 2017
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Ingår i: Australian Journal of Chemistry. - 1445-0038 .- 0004-9425. ; 70:9, s. 997-1005
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Tidskriftsartikel (refereegranskat)abstract
- The demand for catalysts that are highly active and stable for electron-transfer reactions has been boosted by the discovery that [Pt(NH3)4](TCNQF4)2 (TCNQF4≤2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane) is an efficient catalyst. In this work, we prepare and characterize the two related [Pt(NH3)4] 2+ complexes, [Pt(NH3)4](TCNQ)2·(DMF)2 (1) and [Pt(NH3)4] (TCNQ)2 (2). Reaction of [Pt(NH3)4](NO3)2 with LiTCNQ in a mixed solvent (methanol/dimethylformamide, 4:1v/v) gives [Pt(NH3)4] (TCNQ)2·(DMF)2 (1), whereas the same reaction in water affords [Pt(NH3)4](TCNQ)2 (2). 2 has been previously reported. Both 1 and 2 have now been characterized by single-crystal X-ray crystallography, Fourier-transform (FT)IR, Raman and UV-vis spectroscopy, and electrochemistry. Structurally, in 1, the TCNQ1-anions form infinite stacks with a separation between adjacent anions within the stack alternating between 3.12 and 3.42Å. The solvated structure 1 differs from the non-solvated form 2 in that pairs of TCNQ1-anions are clearly displaced from each other. The conductivities of pressed pellets of 1 and 2 are both in the semi-conducting range at room temperature. 2 can be electrochemically synthesized by reduction of a TCNQ-modified electrode in contact with an aqueous solution of [Pt(NH3)4] (NO3)2 via a nucleation growth mechanism. Interestingly, we discovered that 1 and 2 are not catalysts for the ferricyanide and thiosulfate reaction. Li+ and tetraalkylammonium salts of TCNQ1-/2-and TCNQF41-/2-were tested for potential catalytic activity towards ferricyanide and thiosulfate. Only TCNQF41-/2-salts were active, suggesting that the dianion redox level needs to be accessible for efficient catalytic activity and explaining why 1 and 2 are not good catalysts. Importantly, the origin of the catalytic activity of the highly active [Pt(NH3)4](TCNQF4)2 catalyst is now understood, enabling other families of catalysts to be developed for important electron-transfer reactions.
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| 16. |
- Lundstrom, UH, et al.
(författare)
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Barriers and opportunities to increase PD incidence and prevalence: Lessons from a European Survey
- 2021
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 41:6, s. 542-551
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Tidskriftsartikel (refereegranskat)abstract
- Peritoneal dialysis (PD) remains underutilised and unplanned start of dialysis further diminishes the likelihood of patients starting on PD, although outcomes are equal to haemodialysis (HD). Methods: A survey was sent to members of EuroPD and regional societies presenting a case vignette of a 48-year-old woman not previously known to the nephrology department and who arrives at the emergency department with established end-stage kidney disease (unplanned start), asking which dialysis modality would most likely be chosen at their respective centre. We assessed associations between the modality choices for this case vignette and centre characteristics and PD-related practices. Results: Of 575 respondents, 32.8%, 32.2% and 35.0% indicated they would start unplanned PD, unplanned HD or unplanned HD with intention to educate patient on PD later, respectively. Likelihood for unplanned start of PD was only associated with quality of structure of the pre-dialysis program. Structure of pre-dialysis education program, PD program in general, likelihood to provide education on PD to unplanned starters, good collaboration with the PD access team and taking initiatives to enhance home-based therapies increased the likelihood unplanned patients would end up on PD. Conclusions: Well-structured pre-dialysis education on PD as a modality, good connections to dedicated PD catheter placement teams and additional initiatives to enhance home-based therapies are key to grow PD programs. Centres motivated to grow their PD programs seem to find solutions to do so.
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| 17. |
- Shangguan, Siyi, et al.
(författare)
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Health Impact and Cost-Effectiveness of Achieving the National Salt and Sugar Reduction Initiative Voluntary Sugar Reduction Targets in the United States : A Microsimulation Study.
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:17, s. 1362-1376
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative proposed government-supported voluntary national sugar reduction targets. This intervention's potential effects and cost-effectiveness are unclear.METHODS: A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), coded in C++, was used to estimate incremental changes in type 2 diabetes, cardiovascular disease (CVD), quality-adjusted life-years (QALYs), costs, and cost-effectiveness of the US National Salt and Sugar Reduction Initiative policy. The model was run at the individual level, incorporating the annual probability of each person's transition between health statuses on the basis of risk factors. The model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across 3 cycles (2011 through 2016), added sugar-related diseases from meta-analyses, and policy costs and health-related costs from established sources. A simulated nationally representative US population was created and followed until age 100 years or death, with 2019 as the year of intervention start. Findings were evaluated over 10 years and a lifetime from health care and societal perspectives. Uncertainty was evaluated in a 1-way analysis by assuming 50% industry compliance and probabilistic sensitivity analyses through a second-order Monte Carlo approach. Model outputs included averted diabetes cases, CVD events and CVD deaths, QALYs gained, and formal health care cost savings, stratified by age, race, income, and education.RESULTS: Achieving the US National Salt and Sugar Reduction Initiative sugar reduction targets could prevent 2.48 million CVD events, 0.49 million CVD deaths, and 0.75 million diabetes cases; gain 6.67 million QALYs; and save $160.88 billion net costs from a societal perspective over a lifetime. The policy became cost-effective (<150 000/QALYs) at 6 years, highly cost-effective (<50 000/QALYs) at 7 years, and cost-saving at 9 years. Results were robust from a health care perspective, with lower (50%) industry compliance, and in probabilistic sensitivity analyses. The policy could also reduce disparities, with greatest estimated health gains per million adults among Black or Hispanic individuals, lower income, and less educated Americans.CONCLUSIONS: Implementing and achieving the US National Salt and Sugar Reduction Initiative sugar reformation targets could generate substantial health gains, equity gains, and cost savings.
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| 18. |
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| 19. |
- Abrahams-Gessel, Shafika, et al.
(författare)
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Improvements in Hypertension Control in the Rural Longitudinal HAALSI Cohort of South African Adults Aged 40 and Older, From 2014 to 2019
- 2023
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Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 36:6, s. 324-332
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Over half of the South African adults aged 45 years and older have hypertension but its effective management along the treatment cascade (awareness, treatment, and control) remains poorly understood.METHODS: We compared the prevalence of all stages of the hypertension treatment cascade in the rural HAALSI cohort of older adults at baseline and after four years of follow-up using household surveys and blood pressure data. Hypertension was a mean systolic blood pressure >140 mm Hg or diastolic pressure >90 mm Hg, or current use of anti-hypertension medication. Control was a mean blood pressure <140/90 mm Hg. The effects of sex and age on the treatment cascade at follow-up were assessed. Multivariate Poisson regression models were used to estimate prevalence ratios along the treatment cascade at follow-up.RESULTS: Prevalence along the treatment cascade increased from baseline (B) to follow-up (F): awareness (64.4% vs. 83.6%), treatment (49.7% vs. 73.9%), and control (22.8% vs. 41.3%). At both time points, women had higher levels of awareness (B: 70.5% vs. 56.3%; F: 88.1% vs. 76.7%), treatment (B: 55.9% vs. 41.55; F: 79.9% vs. 64.7%), and control (B: 26.5% vs. 17.9%; F: 44.8% vs. 35.7%). Prevalence along the cascade increased linearly with age for everyone. Predictors of awareness included being female, elderly, or visiting a primary health clinic three times in the previous 3 months, and the latter two also predicted hypertension control.CONCLUSIONS: There were significant improvements in awareness, treatment, and control of hypertension from baseline to follow-up and women fared better at all stages, at both time points.
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| 20. |
- Abrahams, Harriët J. G., et al.
(författare)
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Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer : Individual patient data meta-analyses
- 2020
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Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 29:11, s. 1772-1785
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Forskningsöversikt (refereegranskat)abstract
- ObjectivePsychosocial interventions can reduce cancer‐related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta‐analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention‐related characteristics on the effect of psychosocial interventions on cancer‐related fatigue in patients with non‐metastatic breast and prostate cancer.MethodsData were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta‐analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed‐effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008).ResultsStatistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = −0.19 [95% confidence interval (95%CI) = −0.30; −0.08]; prostate cancer: β = −0.11 [95%CI = −0.21; −0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention‐related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = −0.27 [95%CI = −0.40; −0.15]), fatigue‐specific interventions (β = −0.48 [95%CI = −0.79; −0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = −0.85 [95%CI = −1.40; −0.30]).ConclusionsOur findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue.
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| 21. |
- Abrahams, I., et al.
(författare)
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A Combined Total Scattering and Simulation Approach to Analyzing Defect Structure in Bi3YO6
- 2010
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 1520-5002 .- 0897-4756. ; 22:15, s. 4435-4445
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Tidskriftsartikel (refereegranskat)abstract
- The defect structure and electrical properties of the fast oxide ion-conducting solid electrolyte delta-Bi3YO6 have been studied using a combination of total neutron scattering analysis, energy minimization methods, and AC impedance spectroscopy. Conventional structural analysis using the Rietveld method reveals the oxide ions to be distributed over three crystallographic sites at room temperature, with a small change in this distribution at 800 degrees C. Analysis of short-range correlations using a total neutron scattering approach yields information on Bi and Y coordination environments. Careful analysis of the angular distribution functions derived from reverse Monte Carlo modeling of the total scattering data reveals physical evidence for a predominance of vacancy ordering in this system. This ordering is confirmed as the lowest energy configuration in parallel energy minimization simulations.
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| 22. |
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| 23. |
- Benatar, Michael, et al.
(författare)
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Preventing amyotrophic lateral sclerosis : insights from pre-symptomatic neurodegenerative diseases
- 2022
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 145:1, s. 27-44
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Forskningsöversikt (refereegranskat)abstract
- Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. While much is still unknown, advances in other neurodegenerative diseases offer valuable insights. Indeed, it is increasingly clear that the well-recognized clinical syndromes of Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy and frontotemporal dementia are also each preceded by a pre-symptomatic or prodromal period of varying duration, during which the underlying disease process unfolds, with associated compensatory changes and loss of inherent system redundancy. Key insights from these diseases highlight opportunities for discovery in amyotrophic lateral sclerosis. The development of biomarkers reflecting amyloid and tau has led to a shift in defining Alzheimer's disease based on inferred underlying histopathology. Parkinson's disease is unique among neurodegenerative diseases in the number and diversity of non-genetic biomarkers of pre-symptomatic disease, most notably REM sleep behaviour disorder. Huntington's disease benefits from an ability to predict the likely timing of clinically manifest disease based on age and CAG-repeat length alongside reliable neuroimaging markers of atrophy. Spinal muscular atrophy clinical trials have highlighted the transformational value of early therapeutic intervention, and studies in frontotemporal dementia illustrate the differential role of biomarkers based on genotype. Similar advances in amyotrophic lateral sclerosis would transform our understanding of key events in pathogenesis, thereby dramatically accelerating progress towards disease prevention. Deciphering the biology of pre-symptomatic amyotrophic lateral sclerosis relies on a clear conceptual framework for defining the earliest stages of disease. Clinically manifest amyotrophic lateral sclerosis may emerge abruptly, especially among those who harbour genetic mutations associated with rapidly progressive amyotrophic lateral sclerosis. However, the disease may also evolve more gradually, revealing a prodromal period of mild motor impairment preceding phenoconversion to clinically manifest disease. Similarly, cognitive and behavioural impairment, when present, may emerge gradually, evolving through a prodromal period of mild cognitive impairment or mild behavioural impairment before progression to amyotrophic lateral sclerosis. Biomarkers are critically important to studying pre-symptomatic amyotrophic lateral sclerosis and essential to efforts to intervene therapeutically before clinically manifest disease emerges. The use of non-genetic biomarkers, however, presents challenges related to counselling, informed consent, communication of results and limited protections afforded by existing legislation. Experiences from pre-symptomatic genetic testing and counselling, and the legal protections against discrimination based on genetic data, may serve as a guide. Building on what we have learned - more broadly from other pre-symptomatic neurodegenerative diseases and specifically from amyotrophic lateral sclerosis gene mutation carriers - we present a road map to early intervention, and perhaps even disease prevention, for all forms of amyotrophic lateral sclerosis.
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| 24. |
- Chatterjee, S., et al.
(författare)
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Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers
- 2019
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:21-22
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Tidskriftsartikel (refereegranskat)abstract
- While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.
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| 25. |
- Du Toit, Jacques D., et al.
(författare)
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Estimating population level 24-h sodium excretion using spot urine samples in older adults in rural South Africa
- 2023
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Ingår i: Journal of Hypertension. - : Wolters Kluwer. - 0263-6352 .- 1473-5598. ; 41:2, s. 280-287
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: South Africa has introduced regulations to reduce sodium in processed foods. Assessing salt consumption with 24-h urine collection is logistically challenging and expensive. We assess the accuracy of using spot urine samples to estimate 24-h urine sodium (24hrUNa) excretion at the population level in a cohort of older adults in rural South Africa.METHODS: 24hrUNa excretion was measured and compared to that estimated from matched spot urine samples in 399 individuals, aged 40-75 years, from rural Mpumalanga, South Africa. We used the Tanaka, Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT), and Population Mean Volume (PMV) method to predict 24hrUNa at the individual and population level.RESULTS: The population median 24hrUNa excretion from our samples collected in 2017 was 2.6 g (interquartile range: 1.53-4.21) equal to an average daily salt intake of 6.6 g, whereas 65.4% of participants had a salt excretion above the WHO recommended 5 g/day. Estimated population median 24hrUNa derived from the INTERSALT, both with and without potassium, showed a nonsignificant difference of 0.25 g (P = 0.59) and 0.21 g (P = 0.67), respectively. In contrast, the Tanaka, Kawasaki, and PMV formulas were markedly higher than the measured 24hrUNa, with a median difference of 0.51 g (P = 0.004), 0.99 g (P = 0.00), and 1.05 g (P = 0.00) respectively. All formulas however performed poorly when predicting an individual's 24hrUNa.CONCLUSION: In this population, the INTERSALT formulas are a well suited and cost-effective alternative to 24-h urine collection for the evaluation of population median 24hrUNa excretion. This could play an important role for governments and public health agencies in evaluating local salt regulations and identifying at-risk populations.
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| 26. |
- Ferro, Enrico G., et al.
(författare)
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Echocardiographic and Electrocardiographic Abnormalities Among Elderly Adults With Cardiovascular Disease in Rural South Africa
- 2021
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Ingår i: Circulation. Cardiovascular Quality and Outcomes. - : NLM (Medline). - 1941-7713 .- 1941-7705. ; 14:11, s. 1175-1186
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sub-Saharan Africa is undergoing an epidemiological transition fueled by the interaction between infectious and cardiovascular diseases. Our cross-sectional study aimed to characterize the spectrum of abnormalities suggesting end-organ damage on ECG and transthoracic echocardiograms (TTE) among older adults with cardiovascular diseases in rural South Africa.METHODS: The prevalence of ECG and TTE abnormalities was estimated; χ2 analyses and multivariable logistic regressions were performed to test their association with sex, hypertension, and other selected comorbidities.RESULTS: Overall, 729 ECGs and 155 TTEs were completed, with 74 participants completing both. ECG evaluation showed high rates of left ventricular hypertrophy (LVH, 36.5%) and T wave abnormalities (13.6%). TTE evaluation showed high rates of concentric LVH (31.6%), with moderate-severe (56.8%) diastolic dysfunction. Participants with hypertension showed more cardiac remodeling on ECG by LVH (45.4% versus 22.1%, P<0.01), and TTE by concentric LVH (42.5% versus 8.2%, P<0.01) and increased left ventricular mass (58.5% versus 20.4%, P<0.0001). In multivariable logistic regression, systolic blood pressure remained significantly associated with LVH on ECG (adjusted odds ratio, 1.03 per mm Hg [95% CI, 1.03-1.04], P<0.0001) and increased left ventricular mass on TTE (adjusted odds ratio, 1.04 per mm Hg [95% CI, 1.01-1.06], P=0.001). Male participants (n=326, 40.2%) were more likely than females (n=484, 59.8%) to show ECG abnormalities like LVH (45% versus 30.8%, P<0.01), whereas females were more likely to show TTE abnormalities like concentric LVH (40.8% versus 13.5%, P<0.01) and increased left ventricular mass (58.4% versus 23.1%, P<0.0001). Similar results were confirmed in multivariable models.CONCLUSIONS: Our findings suggest that cardiovascular diseases are widespread in rural South Africa, with a larger burden of hypertensive heart disease than previously appreciated, and define the severity of end-organ damage that is already underway. Local health systems must adapt to face the growing burden of hypertension, as suboptimal rates of hypertension diagnosis and treatment may dramatically increase the heart failure burden.
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| 27. |
- Gaziano, Thomas A., et al.
(författare)
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Cardiometabolic risk in a population of older adults with multiple co-morbidities in rural south africa : the HAALSI (Health and Aging in Africa: longitudinal studies of INDEPTH communities) study
- 2017
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: A consequence of the widespread uptake of anti-retroviral therapy (ART) is that the older South African population will experience an increase in life expectancy, increasing their risk for cardiometabolic diseases (CMD), and its risk factors. The long-term interactions between HIV infection, treatment, and CMD remain to be elucidated in the African population. The HAALSI cohort was established to investigate the impact of these interactions on CMD morbidity and mortality among middle-aged and older adults. Methods: We recruited randomly selected adults aged 40 or older residing in the rural Agincourt sub-district in Mpumalanga Province. In-person interviews were conducted to collect baseline household and socioeconomic data, self-reported health, anthropometric measures, blood pressure, high-sensitivity C-reactive protein (hsCRP), HbA1c, HIV-status, and point-of-care glucose and lipid levels. Results: Five thousand fifty nine persons (46.4% male) were enrolled with a mean age of 61.7 +/- 13.06 years. Waist-to- hip ratio was high for men and women (0.92 +/- 0.08 vs. 0.89 +/- 0.08), with 70% of women and 44% of men being overweight or obese. Blood pressure was similar for men and women with a combined hypertension prevalence of 58.4% and statistically significant increases were observed with increasing age. High total cholesterol prevalence in women was twice that observed for men (8.5 vs. 4.1%). The prevalence of self-reported CMD conditions was higher among women, except for myocardial infarction, and women had a statistically significantly higher prevalence of angina (10.82 vs. 6.97%) using Rose Criteria. The HIV- persons were significantly more likely to have hypertension, diabetes, or be overweight or obese than HIV+ persons. Approximately 56% of the cohort had at least 2 measured or self-reported clinical co-morbidities, with HIV+ persons having a consistently lower prevalence of co-morbidities compared to those without HIV. Absolute 10-year risk cardiovascular risk scores ranged from 7.7-9.7% for women and from 12.5-15.3% for men, depending on the risk score equations used. Conclusions: This cohort has high CMD risk based on both traditional risk factors and novel markers like hsCRP. Longitudinal follow-up of the cohort will allow us to determine the long-term impact of increased lifespan in a population with both high HIV infection and CMD risk.
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| 28. |
- Jardim, Thiago Veiga, et al.
(författare)
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Hypertension management in a population of older adults in rural South Africa
- 2017
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 35:6, s. 1283-1289
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Assess awareness, treatment, and control of hypertension, as an indication of its management, in rural South Africa, especially regarding modifiers of these variables. Methods: A population-representative sample of adults aged at least 40 years residing in the rural Agincourt subdistrict (Mpumalanga Province) covered by a long-term health and sociodemographic surveillance system was recruited. In-person interviews, physical exams, and dried blood spots were collected. Hypertension awareness, treatment, and control rates were assessed. A regression model was built to identify predictors of those outcomes. Results: The mean age of the 2884 hypertensive participants was 64.1 +/- 12.7 years. Hypertension awareness rate was 64.4%, treatment among those aware was 89.3 and 45.8% of those treated were controlled. Considering aware and unaware hypertensives, treatment rate was 49.7% and control 22.8%. In the multivariable regression model, awareness was predicted by female sex, age at least 60 years, higher social economic status, prior cardiovascular disease (CVD), nonimmigrant status, literacy, and physical limitation. Improved control among those treated was predicted by age at least 60 years. Blood pressure control among all hypertensive study participants was predicted by female sex, being HIV-negative, age at least 60 years, nonimmigrant status, and prior CVD. Conclusion: High rates of awareness and treatment of hypertension as well as good levels of control were found in this population, probably explained by the long-term surveillance program conducted in the area. Considering the predictors of hypertension management, particular attention should be given to men, residents younger than 60 years, immigrants, and study participants without CVD as these characteristics were predictors of poor outcome.
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| 29. |
- Lee, Yujin, et al.
(författare)
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Health Impact and Cost-Effectiveness of Volume, Tiered, and Absolute Sugar Content Sugar-Sweetened Beverage Tax Policies in the United States : A Microsimulation Study.
- 2020
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 142:6, s. 523-534
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sugar-sweetened beverage taxes are a rapidly growing policy tool and can be based on absolute volume, sugar content tiers, or absolute sugar content. Yet, their comparative health and economic impacts have not been quantified, in particular, tiered or sugar content taxes that provide industry incentives for sugar reduction.METHODS: We estimated incremental changes in diabetes mellitus and cardiovascular disease, quality-adjusted life-years, costs, and cost-effectiveness of 3 sugar-sweetened beverage tax designs in the United States, on the basis of (1) volume ($0.01/oz), (2) tiers (<5 g of added sugar/8 oz: no tax; 5-20 g/8 oz: $0.01/oz; and >20 g/8 oz: $0.02/oz), and (3) absolute sugar content ($0.01 per teaspoon added sugar), each compared with a base case of modest ongoing voluntary industry reformulation. A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey, policy effects and sugar-sweetened beverage-related diseases from meta-analyses, and industry reformulation and health-related costs from established sources.RESULTS: Over a lifetime, the volume, tiered, and absolute sugar content taxes would generate $80.4 billion, $142 billion, and $41.7 billion in tax revenue, respectively. From a healthcare perspective, the volume tax would prevent 850 000 cardiovascular disease (95% CI, 836 000-864 000) and 269 000 diabetes mellitus (265 000-274 000) cases, gain 2.44 million quality-adjusted life-years (2.40-2.48), and save $53.2 billion net costs (52.3-54.1). Health gains and savings were approximately doubled for the tiered and absolute sugar content taxes. Results were robust for societal and government perspectives, at 10 years follow-up, and with lower (50%) tax pass-through. Health gains were largest in young adults, blacks and Hispanics, and lower-income Americans.CONCLUSIONS: All sugar-sweetened beverage tax designs would generate substantial health gains and savings. Tiered and absolute sugar content taxes should be considered and evaluated for maximal potential gains.
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| 30. |
- Lisacek, F., et al.
(författare)
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Databases and associated tools for glycomics and glycoproteomics
- 2017
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Ingår i: High-Throughput Glycomics and Glycoproteomics. Eds: Gordan Lauc & Manfred Wuhrer. - New York : Springer. - 1064-3745. - 9781493964932 - 9781493964918 ; , s. 235-264
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The access to biodatabases for glycomics and glycoproteomics has proven to be essential for current glycobiological research. This chapter presents available databases that are devoted to different aspects of glycobioinformatics. This includes oligosaccharide sequence databases, experimental databases, 3D structure databases (of both glycans and glycorelated proteins) and association of glycans with tissue, disease, and proteins. Specific search protocols are also provided using tools associated with experimental databases for converting primary glycoanalytical data to glycan structural information. In particular, researchers using glycoanalysis methods by U/HPLC (GlycoBase), MS (GlycoWorkbench, UniCarb-DB, GlycoDigest), and NMR (CASPER) will benefit from this chapter. In addition we also include information on how to utilize glycan structural information to query databases that associate glycans with proteins (UniCarbKB) and with interactions with pathogens (Sugar Bind). © Springer Science+Business Media New York 2017.
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| 31. |
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| 32. |
- Martinez, Fernando J., et al.
(författare)
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Effects of baseline symptom burden on treatment response in COPD
- 2019
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Ingår i: International journal of chronic obstructive pulmonary disease. - 1178-2005. ; 14, s. 181-194
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: In symptomatic patients with COPD, the decision whether to initiate maintenance treatment with a single agent or a combination of long-acting bronchodilators remains unclear. Objective: To investigate whether baseline symptomatic status influences response to tiotropium/olodaterol treatment. Materials and methods: Post hoc analysis of the randomized OTEMTO® studies (NCT01964352; NCT02006732), in which patients with moderate-to-severe COPD received placebo, tiotropium 5 µg, tiotropium/olodaterol 2.5/5 µg, or tiotropium/olodaterol 5/5 µg once daily for 12 weeks via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Impact of baseline symptomatic status (modified Medical Research Council [mMRC] score) on response to treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg, or placebo at Week 12 was assessed by St George's Respiratory Questionnaire (SGRQ) total score and response rate, transition dyspnea index (TDI) focal score and response rate, and trough forced expiratory volume in 1 second response. Results: Tiotropium/olodaterol improved SGRQ total scores and response rates compared with placebo and tiotropium for patients with baseline mMRC scores 0-1 and ≥2. For tiotropium/olodaterol vs tiotropium, greater improvements were observed for patients with mMRC ≥2 (SGRQ score adjusted mean treatment difference -3.44 [95% CI: -5.43, -1.46]; P=0.0007; SGRQ response rate ORs 2.09 [95% CI: 1.41, 3.10]; P=0.0002). Dyspnea, measured by TDI score, was consistently improved with tiotropium/olodaterol vs placebo for patients with mMRC scores 0-1 and ≥2 (adjusted mean treatment difference 1.63 [95% CI: 1.06, 2.20]; P<0.0001 and 1.60 [95% CI: 1.09, 2.10]; P<0.0001, respectively). In patients with mMRC scores 0-1 and ≥2, tiotropium/olodaterol consistently improved TDI response rate and lung function vs placebo and tiotropium. Conclusions: Patients with COPD with more severe baseline dyspnea appear to derive greater health status benefit with tiotropium/olodaterol compared with tiotropium alone.
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| 33. |
- van der Sluijs, AV, et al.
(författare)
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Assisted peritoneal dialysis across Europe: Practice variation and factors associated with availability
- 2021
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 41:6, s. 533-541
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Tidskriftsartikel (refereegranskat)abstract
- In Europe, the number of elderly end-stage kidney disease patients is increasing. Few of those patients receive peritoneal dialysis (PD), as many cannot perform PD autonomously. Assisted PD programmes are available in most European countries, but the percentage of patients receiving assisted PD varies considerably. Hence, we assessed which factors are associated with the availability of an assisted PD programme at a centre level and whether the availability of this programme is associated with proportion of home dialysis patients. Methods: An online survey was sent to healthcare professionals of European nephrology units. After selecting one respondent per centre, the associations were explored by χ 2 tests and (ordinal) logistic regression. Results: In total, 609 respondents completed the survey. Subsequently, 288 respondents from individual centres were identified; 58% worked in a centre with an assisted PD programme. Factors associated with availability of an assisted PD programme were Western European and Scandinavian countries (OR: 5.73; 95% CI: 3.07–10.68), non-academic centres (OR: 2.01; 95% CI: 1.09–3.72) and centres with a dedicated team for education (OR: 2.87; 95% CI: 1.35–6.11). Most Eastern & Central European respondents reported that the proportion of incident and prevalent home dialysis patients was <10% (72% and 63%), while 27% of Scandinavian respondents reported a proportion of >30% for both incident and prevalent home dialysis patients. Availability of an assisted PD programme was associated with a higher incidence (cumulative OR: 1.91; 95% CI: 1.21–3.01) and prevalence (cumulative OR: 2.81; 95% CI: 1.76–4.47) of patients on home dialysis. Conclusions: Assisted PD was more commonly offered among non-academic centres with a dedicated team for education across Europe, especially among Western European and Scandinavian countries where higher incidence and prevalence of home dialysis patients was reported.
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