1,276 research outputs found

    Rare behavior of growth processes via umbrella sampling of trajectories

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    We compute probability distributions of trajectory observables for reversible and irreversible growth processes. These results reveal a correspondence between reversible and irreversible processes, at particular points in parameter space, in terms of their typical and atypical trajectories. Thus key features of growth processes can be insensitive to the precise form of the rate constants used to generate them, recalling the insensitivity to microscopic details of certain equilibrium behavior. We obtained these results using a sampling method, inspired by the “s-ensemble” large-deviation formalism, that amounts to umbrella sampling in trajectory space. The method is a simple variant of existing approaches, and applies to ensembles of trajectories controlled by the total number of events. It can be used to determine large-deviation rate functions for trajectory observables in or out of equilibrium

    Abciximab reduces mortality in diabetics following percutaneous coronary intervention

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    AbstractOBJECTIVESWe sought to determine whether abciximab therapy at the time of percutaneous coronary intervention (PCI) would favorably affect one-year mortality in patients with diabetes.BACKGROUNDDiabetics are known to have increased late mortality following PCI.METHODSData from three placebo-controlled trials of PCI, EPIC, EPILOG, and EPISTENT, were pooled. The one-year mortality rate for patients with a clinical diagnosis of diabetes mellitus was compared with the rate for nondiabetic patients treated with either abciximab or placebo.RESULTSIn the 1,462 diabetic patients, abciximab decreased the mortality from 4.5% to 2.5%, p = 0.031, and in the 5,072 nondiabetic patients, from 2.6% to 1.9%, p = 0.099. In patients with the clinical syndrome of insulin resistance—defined as diabetes, hypertension, and obesity—mortality was reduced by abciximab treatment from 5.1% to 2.3%, p = 0.044. The beneficial reduction in mortality with abciximab use in diabetics classified as insulin-requiring was from 8.1% to 4.2%, p = 0.073. Mortality in diabetics who underwent multivessel intervention was reduced from 7.7% to 0.9% with use of abciximab, p = 0.018. In a Cox proportional hazards survival model, the risk ratio for mortality with abciximab use compared with placebo was 0.642 (95% confidence interval 0.458–0.900, p = 0.010).CONCLUSIONSAbciximab decreases the mortality of diabetic patients to the level of placebo-treated nondiabetic patients. This beneficial effect is noteworthy in those diabetic patients who are also hypertensive and obese and in diabetics undergoing multivessel intervention. Besides its potential role in reducing repeat intervention for stented diabetic patients, abciximab therapy should be strongly considered in diabetic patients undergoing PCI to improve their survival

    Soil resources, microbial activity, and primary production across an agricultural ecosystem

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    Includes bibliographical references (pages 169-170).The degree to which soil resource availability is linked to patterns of microbial activity and plant productivity within ecosystems has important consequences for our understanding of how ecosystems are structured and for the management of systems for agricultural production. We studied this linkage in a 48-ha site in southwest Michigan, USA, that had been cultivated and planted to row crops for decades. Prior to seeding the site to genetically identical soybean plants (Glycine max) in early spring, we removed soil samples from ≈600 locations; plant biomass was harvested from these same locations later in the season. Soil samples were analyzed for physical properties (texture, bulk density), chemical properties (moisture, pH, total C, total N, inorganic N), and biological attributes (microbial biomass, microbial population size, respiration potential, and nitrification and N-mineralization potentials). Plant analyses included biomass and C and N contents. Soil resource variability across this long-cultivated site was remarkably high, as was variability in microbial activity and primary productivity. In almost all cases variability exhibited a strong spatially explicit structure: for most properties and processes > 50% of sample variance was spatially dependent at a scale of 5–60 m. Exceptions included microtopography, soil pH, and inorganic P, which were spatially dependent across the entire 1–1200 m range of separation distances examined in this study, and the culturable-bacteria population, which was not spatially autocorrelated at any scale examined. Both topographic relief and soil pH exhibited strongly nested structures, with autocorrelation occurring within two (topography) or more (pH) distinct ranges. Multiple regression analysis showed surprisingly little correlation between biological processes (soybean productivity, soil N turnover, soil respiration), and static soil properties. The best predictor of soybean biomass at late reproductive stages (r2 = 0.42) was a combination of nitrate N, bulk density, inorganic P, N-mineralization rates, and pH. Overall, results suggest a remarkable degree of spatial variability for a pedogenically homogeneous site that has been plowed and cropped mostly as a single field for > 100 yr. Such variability is likely to be generic to most ecosystems and should be carefully evaluated when making inferences about ecological relationships in these systems and when considering alternative sampling and management strategies

    Probing EWSB Naturalness in Unified SUSY Models with Dark Matter

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    We have studied Electroweak Symmetry Breaking (EWSB) fine-tuning in the context of two unified Supersymmetry scenarios: the Constrained Minimal Supersymmetric Model (CMSSM) and models with Non-Universal Higgs Masses (NUHM), in light of current and upcoming direct detection dark matter experiments. We consider both those models that satisfy a one-sided bound on the relic density of neutralinos, Ωχh2<0.12\Omega_{\chi} h^2 < 0.12, and also the subset that satisfy the two-sided bound in which the relic density is within the 2 sigma best fit of WMAP7 + BAO + H0 data. We find that current direct detection searches for dark matter probe the least fine-tuned regions of parameter-space, or equivalently those of lowest Higgs mass parameter ÎŒ\mu, and will tend to probe progressively more and more fine-tuned models, though the trend is more pronounced in the CMSSM than in the NUHM. Additionally, we examine several subsets of model points, categorized by common mass hierarchies; M_{\chi_0} \sim M_{\chi^\pm}, M_{\chi_0} \sim M_{\stau}, M_{\chi_0} \sim M_{\stop_1}, the light and heavy Higgs poles, and any additional models classified as "other"; the relevance of these mass hierarchies is their connection to the preferred neutralino annihilation channel that determines the relic abundance. For each of these subsets of models we investigated the degree of fine-tuning and discoverability in current and next generation direct detection experiments.Comment: 26 pages, 10 figures. v2: references added. v3: matches published versio

    Developing a model of short-term integrated palliative and supportive care for frail older people in community settings: perspectives of older people, carers and other key stakeholders

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    Background: Understanding how best to provide palliative care for frail older people with non-malignant conditions is an international priority. We aimed to develop a community-based episodic model of short-term integrated palliative and supportive care (SIPS) based on the views of service users and other key stakeholders in the United Kingdom. Method: Transparent expert consultations with health professionals, voluntary sector and carer representatives including a consensus survey; and focus groups with older people and carers were used to generate recommendations for the SIPS model. Discussions focused on three key components of the model: potential benefit of SIPS; timing of delivery; and processes of integrated working between specialist palliative care and generalist practitioners. Content and descriptive analysis was employed and findings integrated across the data sources. Findings: We conducted two expert consultations (n=63), a consensus survey (n=42) and three focus groups (n=17). Potential benefits of SIPS included holistic assessment, opportunity for end of life discussion, symptom management, and carer reassurance. Older people and carers advocated early access to SIPS, while other stakeholders proposed delivery based on complex symptom burden. A priority for integrated working was the assignment of a key worker to coordinate care, but the assignment criteria remain uncertain. Interpretation: Key stakeholders agree that a model of SIPS for frail older people with non-malignant conditions has potential benefits within community settings, but differ in opinion on the optimal timing and indications for this service. Our findings highlight the importance of consulting all key stakeholders in model development prior to feasibility evaluation

    ‘They’re more like ordinary stroppy British women’: Attitudes and expectations of maternity care professionals to UK-born ethnic minority women

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    Objective To explore the attitudes and expectations of maternity care professionals to UK-born ethnic minority mothers. Methods Qualitative in-depth interviews with 30 professionals from eight NHS maternity units in England that provide services for large proportions of women of black Caribbean, black African, Indian, Pakistani and Irish descent. Results All the professionals reported providing care to both UK-born and migrant mothers from ethnic minorities. Most of them felt that they could differentiate between UK-born and migrant mothers based mainly on language fluency and accent. ‘Westernized dress’ and ‘freedom’ were also cited as indicators. Overall, professionals found it easier to provide services to UK-born mothers and felt that their needs were more like those of white English mothers than those of migrant mothers. UK-born mothers were generally thought to be assertive and expressive, and in control of care-related decision-making whereas some South Asian Muslim women were thought to be constrained by family influences. Preconceived ideas about ethnic minority mothers' tolerance of pain in labour, use of pharmacological pain relief measures and mode of delivery were recurring themes. Women's education and social class were felt to be major influences on the uptake of maternity care, regardless of ethnicity. Conclusions Professionals appeared to equate the needs of UK-born ethnic minority women with those of white English women. Overall, this has positive implications for care provision. Despite this, specific behavioural expectations and unconscious stereotypical views were evident and have the potential to affect clinical practice

    Metabolomics and lipidomics reveal perturbation of sphingolipid metabolism by a novel anti-trypanosomal 3-(oxazolo[4,5-b]pyridine-2-yl)anilide

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    Introduction: Trypanosoma brucei is the causative agent of human African trypanosomiasis, which is responsible for thousands of deaths every year. Current therapies are limited and there is an urgent need to develop new drugs. The anti-trypanosomal compound, 3-(oxazolo[4,5-b]pyridine-2-yl)anilide (OXPA), was initially identified in a phenotypic screen and subsequently optimized by structure–activity directed medicinal chemistry. It has been shown to be non-toxic and to be active against a number of trypanosomatid parasites. However, nothing is known about its mechanism of action. Objective: Here, we have utilized an untargeted metabolomics approach to investigate the biochemical effects and potential mode of action of this compound in T. brucei. Methods: Total metabolite extracts were analysed by HILIC-chromatography coupled to high resolution mass spectrometry. Results: Significant accumulation of ceramides was observed in OXPA-treated T. brucei. To further understand drug-induced changes in lipid metabolism, a lipidomics method was developed which enables the measurement of hundreds of lipids with high throughput and precision. The application of this LC–MS based approach to cultured bloodstream-form T. brucei putatively identified over 500 lipids in the parasite including glycerophospholipids, sphingolipids and fatty acyls, and confirmed the OXPA-induced accumulation of ceramides. Labelling with BODIPY-ceramide further confirmed the ceramide accumulation following drug treatment. Conclusion: These findings clearly demonstrate perturbation of ceramide metabolism by OXPA and indicate that the sphingolipid pathway is a promising drug target in T. brucei.No Full Tex

    Toxic effects of orally ingested oil from the Deepwater Horizon spill on laughing gulls

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    The explosion of the Deepwater Horizon oil rig released millions of gallons of oil into the environment, subsequently exposing wildlife, including numerous bird species. To determine the effects of MC252 oil to species relevant to the Gulf of Mexico, studies were done examining multiple exposure scenarios and doses. In this study, laughing gulls (Leucophaeus atricilla, LAGU) were offered fish injected with MC252 oil at target doses of 5 or 10 mL/kg bw per day. Dosing continued for 27 days. Of the adult, mixed-sex LAGUs used in the present study, 10 of 20 oil exposed LAGUs survived to the end of the study; a total of 10 of the oil exposed LAGUs died or were euthanized within 20 days of initiation of the study. Endpoints associated with oxidative stress, hepatic total glutathione (tGSH), oxidized glutathione (GSSG) and reduced glutathione (rGSH) significantly increased as mean dose of oil increased, while the rGSH:GSSG ratio showed a non-significant negative trend with oil dose. A significant increase in 3-methyl histidine was found in oil exposed birds when compared to controls indicative of muscle wastage and may have been associated with the gross observation of diminished structural integrity in cardiac tissue. Consistent with previous oil dosing studies in birds, significant changes in liver, spleen, and kidney weight when normalized to body weight were observed. These studies indicate that mortality in response to oil dosing is relatively common and the mortality exhibited by the gulls is consistent with previous studies examining oil toxicity. Whether survival effects in the gull study were associated with weight loss, physiologic effects of oil toxicity, or a behavioral response that led the birds to reject the dosed fish is unknown
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