| 461. |
- Beckmann, Kerri, et al.
(författare)
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Spironolactone use is associated with lower prostate cancer risk : a population-wide case-control study
- 2020
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Ingår i: Prostate Cancer and Prostatic Diseases. - : NATURE PUBLISHING GROUP. - 1365-7852 .- 1476-5608. ; 23:3, s. 527-533
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Tidskriftsartikel (refereegranskat)abstract
- Background Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties. Methods A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides. Results Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings. Conclusion PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.
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| 462. |
- Beheshti, Reza, et al.
(författare)
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Reduction of commercial hematite pellet in isothermal fixed bed-experiments and numerical modelling
- 2016
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Ingår i: Ironmaking & steelmaking. - : Taylor & Francis. - 0301-9233 .- 1743-2812. ; 43:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- In the present work, fixed bed reduction experiments were conducted at 1173 K over a range of H-2/CO ratios from 0.8 to 2.0 and subsequently modelled numerically (R). The model consists of two one-dimensional, isothermal and time dependent models. The gas-solid reactions were kinetically modelled using a modified shrinking core approach, and the equations were solved using the commercial software COMSOL Multiphysics H. The simulation results agree with thermal gravity experimental data with an average difference of 2.5%. A sensitivity analysis was conducted using the numerical model to establish the optimum operational conditions. The effects of the reducing gas ratio and flow rate, pellet radius and porosity, and the total bed height on the overall degree of reduction were also investigated.
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| 463. |
- Bentley, Phillip, et al.
(författare)
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Correction of optical aberrations in elliptic neutron guides
- 2012
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 693, s. 268-275
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Tidskriftsartikel (refereegranskat)abstract
- Modern, nonlinear ballistic neutron guides are an attractive concept in neutron beam delivery and instrumentation because they offer increased performance over straight or linearly tapered guides. However, like other ballistic geometries they have the potential to create significantly non-trivial instrumental resolution functions. We address the source of the most prominent optical aberration, namely coma, and we show that for extended sources the off-axis rays have a different focal length from on-axis rays, leading to multiple reflections in the guide system. We illustrate how the interplay between coma, sources of finite size, and mirrors with non-perfect reflectivity can therefore conspire to produce uneven distributions in the neutron beam divergence, a source of complicated resolution functions. To solve these problems, we propose a hybrid elliptic-parabolic guide geometry. Using this new kind of neutron guide shape, it is possible to condition the neutron beam and remove almost all of the aberrations, whilst providing the same performance in beam current as a standard elliptic neutron guide. We highlight the positive implications for neutron scattering instruments that this new shape can bring. (c) 2012 Elsevier B.V. All rights reserved.
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| 464. |
- Berge, Eivind, et al.
(författare)
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Methods to improve patient recruitment and retention in stroke trials
- 2016
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 11:6, s. 663-676
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Tidskriftsartikel (refereegranskat)abstract
- Background: The success of randomized-controlled stroke trials is dependent on the recruitment and retention of a sufficient number of patients, but fewer than half of all trials meet their target number of patients. Methods: We performed a search and review of the literature, and conducted a survey and workshop among 56 European stroke trialists, to identify barriers, suggest methods to improve recruitment and retention, and make a priority list of interventions that merit further evaluation. Results: The survey and workshop identified a number of barriers to patient recruitment and retention, from patients’ incapacity to consent, to handicaps that prevent patients from participation in trial-specific follow-up. Methods to improve recruitment and retention may include simple interventions with individual participants, funding of research networks, and reimbursement of new treatments by health services only when delivered within clinical trials. The literature review revealed that few methods have been formally evaluated. The top five priorities for evaluation identified in the workshop were as follows: short and illustrated patient information leaflets, nonwritten consent, reimbursement for new interventions only within a study, and monetary incentives to institutions taking part in research (for recruitment); and involvement of patient groups, remote and central follow-up, use of mobile devices, and reminders to patients about their consent to participate (for retention). Conclusions: Many interventions have been used with the aim of improving recruitment and retention of patients in stroke studies, but only a minority has been evaluated. We have identified methods that could be tested, and propose that such evaluations may be nested within on-going clinical trials.
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| 465. |
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| 466. |
- Bianchi, Matteo, et al.
(författare)
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A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds-the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10(-11)). Further characterisation of the candidate region revealed a shared similar to 167 kb risk haplotype (4,915,018-5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.
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| 467. |
- Bizzotto, Roberto, et al.
(författare)
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Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:2, s. 511-518
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. RESULTS: Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. CONCLUSIONS: Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
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| 468. |
- Bjorner, J. B., et al.
(författare)
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Hypophosphatemia attenuates improvements in vitality after intravenous iron treatment in patients with inflammatory bowel disease
- 2024
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Ingår i: Quality of Life Research. - 0962-9343. ; 33:8, s. 2285-2294
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Iron deficiency anemia is common in people with inflammatory bowel disease (IBD), causing deterioration in quality of life, which can be reversed by treatment that increases iron stores and hemoglobin levels. The present post hoc analyses estimate health state utility values for patients with IBD after treatment with ferric derisomaltose or ferric carboxymaltose and evaluate the health domains driving the changes. Methods: SF-36v2 responses were recorded at baseline and day 14, 35, 49, and 70 from 97 patients enrolled in the randomized, double-blind, PHOSPHARE-IBD trial (ClinicalTrials.gov ID: NCT03466983), in which patients with IBD across five European countries were randomly allocated to either ferric derisomaltose or ferric carboxymaltose. Changes in SF-36v2 scale scores and SF-6Dv2 health utility values were analyzed by mixed models. Results: In both treatment arms, SF-6Dv2 utility values and all SF-36v2 scale scores, except Bodily Pain, improved significantly (p = < 0.0001). The improvement in SF-6Dv2 utility values showed no significant treatment group difference. The improvement in utility values was completely explained by improvement in Vitality scores. Vitality scores showed significantly larger improvement with ferric derisomaltose versus ferric carboxymaltose (p = 0.026). Patients with the smallest decrease in phosphate had significantly larger improvements in Vitality scores at each time point (p = < 0.05 for all comparisons) and overall (p = 0.0006). Conclusions: Utility values improved significantly with intravenous iron treatment. Improvement in utility values was primarily driven by Vitality scores, which showed significantly greater improvement in the ferric derisomaltose arm. Smaller decreases in phosphate were associated with significantly higher Vitality scores, suggesting that quality of life improvement is attenuated by hypophosphatemia. The utility values can inform future cost-utility analysis.
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| 469. |
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| 470. |
- Bolton, Ruth N., et al.
(författare)
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Small details that make big differences : A radical approach to consumption experience as a firm's differentiating strategy
- 2014
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Ingår i: Journal of Service Management. - 1757-5818 .- 1757-5826. ; 25:2, s. 253-274
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - Service organizations and marketers have focussed too much of their energy on their core service's performance and too little emphasis on designing a customer journey that enhances the entire customer experience. There is nothing wrong with firms seeking continuous improvement in service quality and customer satisfaction. These efforts are needed for firms to be competitive in the marketplace. The problem occurs when performance levels and service offerings become too similar within an industry, so that price is the only competitive weapon that remains. The purpose of this paper is to argue that in order to break this deadlock, companies need to focus on the small details that make big differences to customers. Design/methodology/approach - The paper builds on interviews with executives in successful service organizations. It provides an analysis of differentiation strategies in diverse service organizations across consumption contexts, nations and cultures around the world. Findings - The paper develops three research propositions and argues for radical approaches to help service organizations truly understand customers and provide service experiences that engage and delight them. The paper argues that the new challenge for marketing is to help companies find and implement these small details to make a large impact on the overall customer experience. Originality/value - In order to truly understand the customer experience, the paper need a holistic view of all interactions customers have with a company. The paper need to understand the customer-firm interactions at all touch points, that is, during search, purchase, consumption and post-consumption. Customer experience involves the customers' cognitive, affective, emotional, social and sensory responses to the firm. The originality of this research lies in the focus on the small details that make a difference to customers during the service process rather than in the final outcome of the service performance.
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