| 1. |
- Bernal, Ximena E., et al.
(författare)
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Empowering Latina scientists
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Adams, Charleen, et al.
(författare)
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Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:1, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
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| 3. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 4. |
- Currow, David, et al.
(författare)
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A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-Arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness : Breathlessness, Exertion and Morphine Sulfate (BEAMS) study protocol
- 2017
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended-release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-Arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. Trial registration number NCT02720822; Pre-results.
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| 5. |
- Currow, David C., et al.
(författare)
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Missed opportunity? Worsening breathlessness as a harbinger of death : A cohort study
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 52:3
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to explore trajectories of breathlessness intensity by function and life-limiting illness diagnosis in the last 3 weeks of life in palliative care patients. A prospective, consecutive cohort study obtained point-of-care data of patients of Silver Chain Hospice Care Service (Perth, Australia) over the period 2011–2014 (n=6801; 51494 data-points). Breathlessness intensity (0–10 numerical rating scale) and physical function (Australia-modified Karnofsky Performance Status (AKPS)) were measured at each visit. Time was anchored at death. Breathlessness trajectory was analysed by physical function and diagnosis using mixed effects regression. Mean±SD age was 71.5±15.1 years and 55.2% were male, most with cancer. The last recorded AKPS was >40 for 26.8%. Breathlessness was worst in people with cardiorespiratory disease and AKPS >40, and breathlessness in the last week of life increased most in this group (adjusted mean 2.92 versus all others 1.51; p=0.0001). The only significant interaction was with diagnosis and function in the last week of life (p<0.0001). Breathlessness is more intense and increases more in people with better function and cardiorespiratory disease immediately before death. Whether there are reversible causes for these people should be explored prospectively. Omitting function from previous population estimates may have overestimated breathlessness intensity for many patients in the days preceding death.
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| 6. |
- Ekström, Magnus, et al.
(författare)
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Breathlessness and sexual activity in older adults : The Australian Longitudinal Study of Ageing
- 2018
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Ingår i: npj Primary Care Respiratory Medicine. - : Springer Science and Business Media LLC. - 2055-1010. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- Sexual activity is important to older adults (65 +). Breathlessness affects about 25% of older adults but impact on sexual activity is unknown. We evaluated the relationships between breathlessness and sexual inactivity and self-reported health among older community-dwelling adults in the Australian Longitudinal Study of Ageing. Associations between self-reported breathlessness (hurrying on level ground or walking up a slight hill) at baseline, self-reported sexual activity, overall health and health compared to people of the same age were explored using logistic regression at baseline and 2 years, adjusted for potential confounders (age, sex, marital status, smoking status and co-morbidities). Of 798 participants (mean age 76.4 years [SD, 5.8] 65 to 103; 53% men, 73% married), 688 (86.2%) had 2-year follow-up data. People with breathlessness had higher prevalence and duration of sexual inactivity (77.7% vs. 65.6%; p < 0.001; 12 [IQR, 5-17] vs. 9.5 [IQR, 5-16] years; p = 0.043). Breathlessness was associated with more sexual inactivity, (adjusted OR 1.75; [95% CI] 1.24-2.45), worse health (adjusted OR 2.02; 1.53-2.67) and worse health compared to peers (adjusted OR 1.72; 1.25-2.38). Baseline breathlessness did not predict more sexual inactivity at 2 years. In conclusion, breathlessness contributes to sexual inactivity and worse perceived health in older adults, which calls for improved assessment and management.
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| 7. |
- Ferreira, Diana H., et al.
(författare)
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Extended-Release Morphine for Chronic Breathlessness in Pulmonary Arterial Hypertension—A Randomized, Double-Blind, Placebo-Controlled, Crossover Study
- 2018
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Ingår i: Journal of Pain and Symptom Management. - : Elsevier BV. - 0885-3924. ; 56:4, s. 483-492
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Tidskriftsartikel (refereegranskat)abstract
- Context: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH. Objectives: This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness. Methods: Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness “right now”—morning and evening—measured with a Visual Analogue Scale. Secondary end points included additional breathlessness measures, quality of life, function, harms, and blinded treatment preference (ACTRN12609000209291). Results: Within a period of seven years, 50 patients were assessed in detail and 23 (46%) were randomized (despite broad eligibility criteria). Four participants withdrew while taking morphine. Nineteen participants completed the study. Breathlessness “right now” was higher on morphine compared with placebo both for morning [mean (M) ± SD 31.7 ± 25 mm vs. 26.9 ± 22 mm; effect size (80% CI) = −0.22 (−0.6 to 0.2)] and evening [(M ± SD 33.5 ± 28 mm vs. 25.6 ± 21 mm; effect size (80% CI) = −0.33 (−0.8 to 0.1)]. All secondary measures of breathlessness were higher with morphine as were nausea and constipation. Conclusion: This study does not support a Phase III study of ER morphine for people with PAH-associated chronic breathlessness. Recruiting to the target sample size was difficult, the direction of effect in every measure of breathlessness favored placebo and morphine generated more harms.
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| 8. |
- Hawkins, Stephen J., et al.
(författare)
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The Intertidal Zone of the North-East Atlantic Region
- 2019
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Ingår i: Interactions in the Marine Benthos: Global Patterns and Processes (Systematics Association Special Volume Series, pp. 7-46). - : Cambridge university press. - 9781108416085
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Bokkapitel (refereegranskat)abstract
- The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
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| 9. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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