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- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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- Friman, S., et al.
(författare)
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Sotrastaurin, a Novel Small Molecule Inhibiting Protein-Kinase C : Randomized Phase II Study in Renal Transplant Recipients
- 2011
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 11:7, s. 1444-1455
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Tidskriftsartikel (refereegranskat)abstract
- Sotrastaurin, a selective protein-kinase-C inhibitor, blocks early T-cell activation through a calcineurin-independent mechanism. In this study, de novo renal transplant recipients with immediate graft function were randomized 1: 2 to tacrolimus (control, n = 44) or sotrastaurin (300 mg b.i.d.; n = 81). All patients received basiliximab, mycophenolic acid (MPA) and steroids. The primary endpoint was the composite of treated biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up at month 3. The main safety assessment was estimated glomerular filtration rate (eGFR); modification of diet in renal disease (MDRD) at month 3. Composite efficacy failure at month 3 was higher for the sotrastaurin versus control regimen (25.7% vs. 4.5%, p = 0.001), driven by higher BPAR rates (23.6% vs. 4.5%, p = 0.003), which led to early study termination. Median (+/- standard deviation [SD]) eGFR was higher for sotrastaurin versus control at all timepoints from day 7 (month 3: 59.0 +/- 22.3 vs. 49.5 +/- 17.7 mL/min/1.73 m(2), p = 0.006). The most common adverse events were gastrointestinal disorders (control: 63.6%; sotrastaurin: 88.9%) which led to study-medication discontinuation in two sotrastaurin patients. This study demonstrated a lower degree of efficacy but better renal function with the calcineurin-inhibitor-free regimen of sotrastaurin+MPA versus the tacrolimus-based control. Ongoing studies are evaluating alternative sotrastaurin regimens.
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- Abrams, M. B., et al.
(författare)
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A Standards Organization for Open and FAIR Neuroscience : the International Neuroinformatics Coordinating Facility
- 2021
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Ingår i: Neuroinformatics. - : Springer Nature. - 1539-2791 .- 1559-0089.
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Tidskriftsartikel (refereegranskat)abstract
- There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.
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- Hemingway, H, et al.
(författare)
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The effectiveness and cost-effectiveness of biomarkers for the prioritisation of patients awaiting coronary revascularisation: a systematic review and decision model.
- 2010
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Ingår i: Health Technology Assessment. - : National Coordinating Centre for Health Technology Assessment. - 1366-5278 .- 2046-4924. ; 14:9, s. 1-178
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the effectiveness and cost-effectiveness of a range of strategies based on conventional clinical information and novel circulating biomarkers for prioritising patients with stable angina awaiting coronary artery bypass grafting (CABG).DATA SOURCES: MEDLINE and EMBASE were searched from 1966 until 30 November 2008.REVIEW METHODS: We carried out systematic reviews and meta-analyses of literature-based estimates of the prognostic effects of circulating biomarkers in stable coronary disease. We assessed five routinely measured biomarkers and the eight emerging (i.e. not currently routinely measured) biomarkers recommended by the European Society of Cardiology Angina guidelines. The cost-effectiveness of prioritising patients on the waiting list for CABG using circulating biomarkers was compared against a range of alternative formal approaches to prioritisation as well as no formal prioritisation. A decision-analytic model was developed to synthesise data on a range of effectiveness, resource use and value parameters necessary to determine cost-effectiveness. A total of seven strategies was evaluated in the final model.RESULTS: We included 390 reports of biomarker effects in our review. The quality of individual study reports was variable, with evidence of small study (publication) bias and incomplete adjustment for simple clinical information such as age, sex, smoking, diabetes and obesity. The risk of cardiovascular events while on the waiting list for CABG was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients with a mean of 59 days at risk). Risk factors associated with an increased risk, and included in the basic risk equation, were age, diabetes, heart failure, previous myocardial infarction and involvement of the left main coronary artery or three-vessel disease. The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information. Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate (eGFR) was cost-effective. These results were robust to most alternative scenarios investigating other sources of uncertainty. However, the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein (CRP) was potentially sensitive to the cost of the CRP test itself (assumed to be 6 pounds in the base-case scenario).CONCLUSIONS: Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes. The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker (eGFR). The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP, singly or in combination with other biomarkers, in terms of waiting list prioritisation is unlikely to be cost-effective.
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| 20. |
- Irwin, D. E., et al.
(författare)
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Overactive bladder is associated with erectile dysfunction and reduced sexual quality of life in men
- 2008
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 5:12, s. 2904-10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. The prevalence of sexual dysfunction, including erectile dysfunction (ED), is greater in men with lower urinary tract symptoms (LUTS), including overactive bladder (OAB), than in men without LUTS. Aim. To evaluate the prevalence of ED, the impact of urinary symptoms on sexual activity and sexual enjoyment, and sexual satisfaction in men with OAB. Methods. A nested case-control analysis was performed on data from a subset of men with (cases) and without (controls) OAB frequency-matched for age (5-year age strata) and country from the EPIC study. Respondents were asked about OAB symptoms (using the 2002 International Continence Society [ICS] definitions) and sexual activity. Sexually active respondents were asked about ED, sexual enjoyment, and overall satisfaction with their sex lives. Conditional logistic regression was used to assess factors associated with ED. Main Outcome Measures. The percentage of cases and controls reporting ED, a reduction in the frequency of sexual activity or enjoyment of sexual activity because of urinary symptoms, and overall satisfaction with their sex lives was determined for cases and controls. Results. A total of 502 cases and 502 controls were matched for age strata and country. Significantly more cases (14%) reported reduced sexual activity because of urinary symptoms compared with controls (4%; P
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| 21. |
- Irwin, D. E., et al.
(författare)
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Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study
- 2006
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Ingår i: Eur Urol. - : Elsevier BV. - 0302-2838. ; 50:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Estimate the prevalence of urinary incontinence (UI), overactive bladder (OAB), and other lower urinary tract symptoms (LUTS) among men and women in five countries using the 2002 International Continence Society (ICS) definitions. METHODS: This population-based, cross-sectional survey was conducted between April and December 2005 in Canada, Germany, Italy, Sweden, and the United Kingdom using computer-assisted telephone interviews. A random sample of men and women aged >/= 18 yr residing in the five countries and who were representative of the general populations in these countries was selected. Using 2002 ICS definitions, the prevalence estimates of storage, voiding, and postmicturition LUTS were calculated. Data were stratified by country, age cohort, and gender. RESULTS: A total of 19,165 individuals agreed to participate; 64.3% reported at least one LUTS. Nocturia was the most prevalent LUTS (men, 48.6%; women, 54.5%). The prevalence of storage LUTS (men, 51.3%; women, 59.2%) was greater than that for voiding (men, 25.7%; women, 19.5%) and postmicturition (men, 16.9%; women, 14.2%) symptoms combined. The overall prevalence of OAB was 11.8%; rates were similar in men and women and increased with age. OAB was more prevalent than all types of UI combined (9.4%). CONCLUSIONS: The EPIC study is the largest population-based survey to assess prevalence rates of OAB, UI, and other LUTS in five countries. To date, this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions. The results indicate that these symptoms are highly prevalent in the countries surveyed.
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- Galluzzi, L, et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Forskningsöversikt (refereegranskat)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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| 34. |
- Henriksson, Martin, et al.
(författare)
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Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery
- 2010
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Ingår i: BRITISH MEDICAL JOURNAL. - : BMJ. - 0959-535X. ; 340
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. Design Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. Data sources Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. Results The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10 000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of 20 pound 000-30 pound 000 ((sic)22 000-(sic)33 000; $32 000-$48 000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was andlt;410 pound compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100 000 patients at an additional cost of 245 pound 000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. Conclusion Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches.
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| 37. |
- Irwin, D. E., et al.
(författare)
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Understanding the elements of overactive bladder: questions raised by the EPIC study
- 2008
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Ingår i: BJU International. - 1464-410X. ; 101:11, s. 1381-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare the prevalence of frequency and nocturia and the bother they impose in a population-based sample of men and women using current International Continence Society (ICS) definitions of lower urinary tract symptoms (LUTS) and commonly used alternative definitions of these LUTS to emphasize the importance of standardizing the definitions when evaluating overactive bladder (OAB) syndrome; we also describe the spectrum of LUTS and bother they impose in this population with OAB. SUBJECTS AND METHODS: Several validated disease-specific measures were used in a population-based, cross-sectional telephone survey of adults aged >or=18 years in five countries. The population with OAB was defined as those participants who answered 'yes' to questions about urgency or urgency urinary incontinence according to ICS standards. The prevalence of daytime frequency and nocturia within the OAB population was examined using two different criteria for each symptom. Frequency was defined using the current ICS definition (i.e. subject's perception of whether they urinated too often during the day) or more than eight daytime voids. Nocturia was defined according to the ICS definition of having to wake once or more per night to void and using the threshold of waking twice or more per night to urinate. Urinary symptom bother within the OAB population was compared using the different criteria for frequency and nocturia. RESULTS: In all, 1434 participants (502 men and 932 women) were classified as having OAB; 31% of men and 25% of women with OAB had daytime frequency consistent with the ICS definition. The ICS-defined frequency identified a population with a varied distribution of reported daytime voiding frequencies; most respondents reported frequencies below the threshold of nine daytime voids. The ICS-defined daytime frequency was reported as bothersome by more than half of the OAB population (46% of men, 66% of women). Of the OAB population, approximately 75% reported one or more nocturia episodes per night, and approximately 40% reported two or more per night. The proportion of the OAB population that was bothered by nocturia increased markedly as the number of nocturia episodes increased. Among those with OAB, the most prevalent combination of OAB symptoms was urgency and nocturia. More than half of those with OAB reported urgency combined with three or more other LUTS (including voiding and postmicturition symptoms), and the number of LUTS reported increased with age. The proportion of the population reporting symptom bother increased as the number of reported LUTS in that population increased. CONCLUSIONS: The ICS definitions for daytime frequency as 'the subject's perception of urinating too often' and for nocturia as 'one or more episodes per night' adequately described bladder symptoms within the OAB population when assessed by the level of symptom bother. Urgency was uncommon in isolation and did not alone impose as high a level of bother as when combined with other LUTS. In this population, the most predominant manifestation of OAB was a combination of urgency with one or more other OAB symptoms. Symptom bother became more common as the number of symptoms reported increased. LUTS other than the defining symptoms of OAB were also highly prevalent within the OAB population.
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- Mohamed, Awaz, et al.
(författare)
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Securing Nature's Contributions to People requires at least 20%-25% (semi-)natural habitat in human-modified landscapes
- 2024
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Ingår i: One Earth. - 2590-3330 .- 2590-3322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The cascading effects of biodiversity decline on human well-being present a pressing challenge for sustainable development. Conservation efforts often prioritize safeguarding specific species, habitats, or intact ecosystems but overlook biodiversity's fundamental role in providing Nature's Contributions to People (NCP) in human -modified landscapes. Here, we systematically review 154 peer -reviewed studies to estimate the minimum levels of (semi -)natural habitat quantity, quality, and spatial configuration needed in human -modified landscapes to secure functional integrity essential for sustaining NCP provision. We find that the provision of multiple NCP is threatened when (semi -)natural habitat in the landscape falls below an area of 20%- 25% for each km2. Five NCP almost completely disappear below a level of 10% habitat. The exact quantity, quality, and spatial configuration of habitat required depends on local context and specific NCP. Today, about two-thirds of human -modified lands have insufficient (semi -)natural habitat, requiring action for NCP regeneration. Our findings serve as a generic guideline to target conservation actions outside natural areas.
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| 48. |
- Sandstrom, Malin, et al.
(författare)
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Recommendations for repositories and scientific gateways from a neuroscience perspective
- 2022
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Digital services such as repositories and science gateways have become key resources for the neuroscience community, but users often have a hard time orienting themselves in the service landscape to find the best fit for their particular needs. INCF has developed a set of recommendations and associated criteria for choosing or setting up and running a repository or scientific gateway, intended for the neuroscience community, with a FAIR neuroscience perspective.
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- Sievert, Karl-Dietrich, et al.
(författare)
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Can we prevent incontinence? ICI-RS 2011.
- 2012
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Ingår i: Neurourology and urodynamics. - : Wiley. - 1520-6777 .- 0733-2467. ; 31:3, s. 390-9
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Tidskriftsartikel (refereegranskat)abstract
- A review of the current state of research with regard to prevention of incontinence.
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