637 research outputs found

    Uncertainties in projecting climate-change impacts in marine ecosystems

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    Projections of the impacts of climate change on marine ecosystems are a key prerequisite for the planning of adaptation strategies, yet theyare inevitablyassociated withuncertainty.Identifying,quantifying,andcommunicatingthisuncertaintyis keytobothevaluatingtherisk associated with a projection and building confidence in its robustness. Wereview howuncertainties in such projections are handled in marine science. We employan approach developedin climatemodelling by breaking uncertainty down into(i) structural (model) uncertainty,(ii) initialization and internalvariabilityuncertainty,(iii)parametricuncertainty,and(iv)scenariouncertainty.Foreachuncertaintytype,wethenexaminethecurrent state-of-the-art in assessing and quantifying its relative importance. We consider whether the marine scientific community has addressed these types of uncertainty sufficiently and highlight the opportunities and challenges associated with doing a better job. We find that even within a relatively small field such as marine science, there are substantial differences between subdisciplines in the degree of attention given to each type of uncertainty. We find that initialization uncertainty is rarely treated explicitly and reducing this type of uncertainty may deliver gainsontheseasonal-to-decadaltime-scale.Weconcludethatallpartsofmarinesciencecouldbenefitfromagreaterexchangeofideas,particularly concerningsuchauniversalproblemsuchasthetreatmentofuncertainty.Finally,marinescienceshouldstrivetoreachthepointwherescenario uncertainty is the dominant uncertainty in our projections

    The role of mentorship in protege performance

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    The role of mentorship on protege performance is a matter of importance to academic, business, and governmental organizations. While the benefits of mentorship for proteges, mentors and their organizations are apparent, the extent to which proteges mimic their mentors' career choices and acquire their mentorship skills is unclear. Here, we investigate one aspect of mentor emulation by studying mentorship fecundity---the number of proteges a mentor trains---with data from the Mathematics Genealogy Project, which tracks the mentorship record of thousands of mathematicians over several centuries. We demonstrate that fecundity among academic mathematicians is correlated with other measures of academic success. We also find that the average fecundity of mentors remains stable over 60 years of recorded mentorship. We further uncover three significant correlations in mentorship fecundity. First, mentors with small mentorship fecundity train proteges that go on to have a 37% larger than expected mentorship fecundity. Second, in the first third of their career, mentors with large fecundity train proteges that go on to have a 29% larger than expected fecundity. Finally, in the last third of their career, mentors with large fecundity train proteges that go on to have a 31% smaller than expected fecundity.Comment: 23 pages double-spaced, 4 figure

    Induction immunosuppression in adults undergoing liver transplantation: a network meta-analysis

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    BACKGROUND: Liver transplantation is considered the definitive treatment for people with liver failure. As part of post-liver transplantation management, immunosuppression (suppressing the host immunity) is given to prevent graft rejections. Immunosuppressive drugs can be classified into those that are used for a short period during the beginning phase of immunosuppression (induction immunosuppression) and those that are used over the entire lifetime of the individual (maintenance immunosuppression), because it is widely believed that graft rejections are more common during the first few months after liver transplantation. Some drugs such as glucocorticosteroids may be used for both induction and maintenance immunosuppression because of their multiple modalities of action. There is considerable uncertainty as to whether induction immunosuppression is necessary and if so, the relative efficacy of different immunosuppressive agents. OBJECTIVES: To assess the comparative benefits and harms of different induction immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different induction immunosuppressive regimens according to their safety and efficacy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until July 2019 to identify randomised clinical trials in adults undergoing liver transplantation. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults undergoing liver transplantation. We excluded randomised clinical trials in which participants had multivisceral transplantation and those who already had graft rejections. DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, and hazard ratio (HR) with 95% credible intervals (CrIs) based on an available case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS: We included a total of 25 trials (3271 participants; 8 treatments) in the review. Twenty-three trials (3017 participants) were included in one or more outcomes in the review. The trials that provided the information included people undergoing primary liver transplantation for various indications and excluded those with HIV and those with renal impairment. The follow-up in the trials ranged from three to 76 months, with a median follow-up of 12 months among trials. All except one trial were at high risk of bias, and the overall certainty of evidence was very low. Overall, approximately 7.4% of people who received the standard regimen of glucocorticosteroid induction died and 12.2% developed graft failure. All-cause mortality and graft failure was lower with basiliximab compared with glucocorticosteroid induction: all-cause mortality (HR 0.53, 95% CrI 0.31 to 0.93; network estimate, based on 2 direct comparison trials (131 participants; low-certainty evidence)); and graft failure (HR 0.44, 95% CrI 0.28 to 0.70; direct estimate, based on 1 trial (47 participants; low-certainty evidence)). There was no evidence of differences in all-cause mortality and graft failure between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). There was also no evidence of differences in serious adverse events (proportion), serious adverse events (number), renal failure, any adverse events (proportion), any adverse events (number), liver retransplantation, graft rejections (any), or graft rejections (requiring treatment) between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the studies reported health-related quality of life. FUNDING: the source of funding for 14 trials was drug companies who would benefit from the results of the study; two trials were funded by neutral organisations who have no vested interests in the results of the study; and the source of funding for the remaining nine trials was unclear. AUTHORS' CONCLUSIONS: Based on low-certainty evidence, basiliximab induction may decrease mortality and graft failure compared to glucocorticosteroids induction in people undergoing liver transplantation. However, there is considerable uncertainty about this finding because this information is based on small trials at high risk of bias. The evidence is uncertain about the effects of different induction immunosuppressants on other clinical outcomes, including graft rejections. Future randomised clinical trials should be adequately powered, employ blinding, avoid post-randomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, graft failure, and health-related quality of life

    Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

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    <div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

    Ecoregional Analysis of Nearshore Sea-Surface Temperature in the North Pacific

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    The quantification and description of sea surface temperature (SST) is critically important because it can influence the distribution, migration, and invasion of marine species; furthermore, SSTs are expected to be affected by climate change. To better understand present temperature regimes, we assembled a 29-year nearshore time series of mean monthly SSTs along the North Pacific coastline using remotely-sensed satellite data collected with the Advanced Very High Resolution Radiometer (AVHRR) instrument. We then used the dataset to describe nearshore (<20 km offshore) SST patterns of 16 North Pacific ecoregions delineated by the Marine Ecoregions of the World (MEOW) hierarchical schema. Annual mean temperature varied from 3.8°C along the Kamchatka ecoregion to 24.8°C in the Cortezian ecoregion. There are smaller annual ranges and less variability in SST in the Northeast Pacific relative to the Northwest Pacific. Within the 16 ecoregions, 31–94% of the variance in SST is explained by the annual cycle, with the annual cycle explaining the least variation in the Northern California ecoregion and the most variation in the Yellow Sea ecoregion. Clustering on mean monthly SSTs of each ecoregion showed a clear break between the ecoregions within the Warm and Cold Temperate provinces of the MEOW schema, though several of the ecoregions contained within the provinces did not show a significant difference in mean seasonal temperature patterns. Comparison of these temperature patterns shared some similarities and differences with previous biogeographic classifications and the Large Marine Ecosystems (LMEs). Finally, we provide a web link to the processed data for use by other researchers

    Measuring the Meltdown: Drivers of Global Amphibian Extinction and Decline

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    Habitat loss, climate change, over-exploitation, disease and other factors have been hypothesised in the global decline of amphibian biodiversity. However, the relative importance of and synergies among different drivers are still poorly understood. We present the largest global analysis of roughly 45% of known amphibians (2,583 species) to quantify the influences of life history, climate, human density and habitat loss on declines and extinction risk. Multi-model Bayesian inference reveals that large amphibian species with small geographic range and pronounced seasonality in temperature and precipitation are most likely to be Red-Listed by IUCN. Elevated habitat loss and human densities are also correlated with high threat risk. Range size, habitat loss and more extreme seasonality in precipitation contributed to decline risk in the 2,454 species that declined between 1980 and 2004, compared to species that were stable (n = 1,545) or had increased (n = 28). These empirical results show that amphibian species with restricted ranges should be urgently targeted for conservation

    Assessing the information desire of patients with advanced cancer by providing information with a decision aid, which is evaluated in a randomized trial: a study protocol

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    Contains fulltext : 95653.pdf (publisher's version ) (Open Access)BACKGROUND: There is a continuing debate on the desirability of informing patients with cancer and thereby involving them in treatment decisions. On the one hand, information uptake may be hampered, and additional stress could be inflicted by involving these patients. On the other hand, even patients with advanced cancer desire information on risks and prognosis. To settle the debate, a decision aid will be developed and presented to patients with advanced disease at the point of decision making. The aid is used to assess the amount of information desired. Factors related to information desire are explored, as well as the ability of the medical oncologist to judge the patient's information desire. The effects of the information on patient well-being are assessed by comparing the decision aid group with a usual care group. METHODS/DESIGN: This study is a randomized controlled trial of patients with advanced colorectal, breast, or ovarian cancer who have started treatment with first-line palliative chemotherapy. The trial will consist of 100 patients in the decision aid group and 70 patients in the usual care group. To collect complete data of 170 patients, 246 patients will be approached for the study. Patients will complete a baseline questionnaire on sociodemographic data, well-being measures, and psychological measures, believed to predict information desire. The medical oncologist will judge the patient's information desire. After disease progression is diagnosed, the medical oncologist offers the choice between second-line palliative chemotherapy plus best supportive care (BSC) and BSC alone. Randomization will take place to determine whether patients will receive usual care (n = 70) or usual care and the decision aid (n = 100). The aid offers information about the potential risks and benefits of both treatment options, in terms of adverse events, tumour response, and survival. Patients decide for each item whether they desire the information or not. Two follow-up questionnaires will evaluate the effect of the decision aid. DISCUSSION: This study attempts to settle the debate on the desirability of informing patients with cancer. In contrast to several earlier studies, we will actually deliver information on treatment options to patients at the point of decision making
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