In this paper, we provide a unified approach to simulate diffusion bridges. The proposed method covers a wide range of processes including univariate and multivariate diffusions, and the diffusions ...can be either time-homogeneous or time-inhomogeneous. We provide a theoretical framework for the proposed method. In particular, using the parametrix representations we show that the approximated probability transition density function converges to that of the true diffusion, which in turn implies the convergence of the approximation. Unlike most of the methods proposed in the literature, our approach does not involve acceptance-rejection mechanics. That is, it is acceptance-rejection free. Extensive numerical examples are provided for illustration and demonstrate the accuracy of the proposed method.
Some of the highest-transition-temperature superconductors across various materials classes exhibit linear-in-temperature 'strange metal' or 'Planckian' electrical resistivities in their normal ...state. It is thus believed by many that this behavior holds the key to unlock the secrets of high-temperature superconductivity. However, these materials typically display complex phase diagrams governed by various competing energy scales, making an unambiguous identification of the physics at play difficult. Here we use electrical resistivity measurements into the micro-Kelvin regime to discover superconductivity condensing out of an extreme strange metal state-with linear resistivity over 3.5 orders of magnitude in temperature. We propose that the Cooper pairing is mediated by the modes associated with a recently evidenced dynamical charge localization-delocalization transition, a mechanism that may well be pertinent also in other strange metal superconductors.
Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with ...amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.
We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks.
A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval CI, 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (-0.42 log10 colony-forming units CFU per milliliter per day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy.
Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.).
Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture ...Risk Calculator in a Norwegian cohort.
The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed. Reclassification analysis was used to compare the models performance.
The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities of hip fracture in those with fracture was 2.8 (women) to 3.1 times (men) higher than those without fracture. There was a close agreement between predicted and observed risk in both sexes and up to the fifth quintile. Among those in the highest quintile of risk, the models over-estimated the risk of fracture. Models with BMD performed better than models with body weight in correct classification of risk in individuals with and without fracture. The overall net decrease in reclassification of the model with weight compared to the model with BMD was 10.6% (p = 0.008) in women and 17.2% (p = 0.001) in men for osteoporotic fractures, and 13.3% (p = 0.07) in women and 17.5% (p = 0.09) in men for hip fracture.
The Garvan Fracture Risk Calculator is valid and clinically useful in identifying individuals at high risk of fracture. The models with BMD performed better than those with body weight in fracture risk prediction.
Recent in vitro evidence suggests a link between vitamin D status and the risk of tuberculosis (TB). This study sought to examine the association between vitamin D status, parathyroid hormone (PTH) ...and the risk of TB in a Vietnamese population.
The study was designed as a matched case-control study, which involved 166 TB patients (113 men and 53 women), who were age-and-sex matched with 219 controls (113 men and 106 women). The average age of men and women was 49 and 50, respectively. TB was diagnosed by the presence of acid-fast bacilli on smears from sputum, and the isolation of M. tuberculosis. All patients were hospitalized for treatment in a TB specialist hospital. Controls were randomly drawn from the general community within the Ho Chi Minh, Vietnam. 25-hydroxyvitamin D 25(OH)D and PTH was measured prior to treatment by an electrochemiluminescence immunoassay (ECLIA) on a Roche Elecsys. A serum level of 25(OH)D below 30 ng/mL was deemed to be vitamin D insufficient.
The prevalence of vitamin D insufficiency was 35.4% in men with TB and 19.5% in controls (P = 0.01). In women, there were no significant differences in serum 25(OH)D and serum PTH levels between TB patients and controls. The prevalence of vitamin D insufficiency in women with TB (45.3%) was not significantly different from those without TB (47.6%; P = 0.91). However, in both genders, serum calcium levels in TB patients were significantly lower than in non-TB individuals. Smoking (odds ratio OR 1.25; 95% confidence interval CI 1.10 - 14.7), reduced 25(OH)D (OR per standard deviation SD: 1.14; 95% CI 1.07 - 10.7) and increased PTH (OR per SD 1.13; 95% CI 1.05 - 10.4) were independently associated with increased risk of TB in men.
These results suggest that vitamin D insufficiency was a risk factor for tuberculosis in men, but not in women. However, it remains to be established whether the association is a causal relationship.
BACKGROUND: The association between vegetarian diets and bone mineral density (BMD) is controversial because of conflicting findings from previous studies. OBJECTIVE: The aim of this study was to ...estimate the effect of vegetarian diets on BMD by using a meta-analytic approach. DESIGN: A systematic electronic literature search was conducted to identify all relevant articles on the association between vegetarian diet and BMD. Nine studies of 2749 subjects (1880 women and 869 men) were included in the analysis. Traditional and Bayesian methods of meta-analysis were applied to synthesize the data. RESULTS: Overall, BMD was almost equal to4% lower in vegetarians than in omnivores (95% CI: 2%, 7%) at both the femoral neck and the lumbar spine. Compared with omnivores, vegans had a significantly lower lumbar spine BMD (6% lower; 95% CI: 2%, 9%), which was more pronounced than in lactoovovegetarians (2% lower; 95% CI: 1%, 4%). The probability that BMD was greater-than-or-equal5% lower in vegetarians than in omnivores (or almost equal to0.3 SD) was 42% for the femoral neck and 32% for the lumbar spine. There was no evidence of publication bias. There was a moderate degree of between-study heterogeneity; the coefficient of heterogeneity varied between 46% and 51%. CONCLUSION: The results suggest that vegetarian diets, particularly vegan diets, are associated with lower BMD, but the magnitude of the association is clinically insignificant.
The failure of soft rocks is highly concerned in both research and practice due to the vulnerability of materials and its involvement in a wide range of foundation and mine collapses. Different ...methods have been suggested to study the fracture characteristics of soft rocks. In this study, a discrete-based modelling method is proposed, as an alternative to existing continuum methods, to analyse the fracturing behaviour of soft rocks. A new cohesive model coupling damage mechanics with plasticity theory is formulated to characterise the failure mechanisms of cement bridges between aggregates in the materials. In conjunction with the discrete element method (DEM), the proposed modelling method can produce realistic modelling of soft rock failure, demonstrated through good agreements between experimental and numerical results in both specimen responses and crack patterns. Based on this, further analyses of soft rock failure are carried out, focusing on the influence of specimen geometries on the material fracture toughness measured in a semi-circular bending test. The simulation results agree well with their experimental counterparts while being less scattered than the experimental data. This demonstrates the effectiveness of the proposed method in characterising fracture properties of soft rocks and opens more potentials for a better understanding of soft rock failure.
•Failure of soft rocks can be effectively captured using a new cohesive model combined with DEM.•The combined damage-plasticity cohesive model can describe well the degradation of cement bridges in soft rocks.•This facilitates the characterisation of soft rock failure for better understanding and design.
HbA1c has been introduced as a complementary diagnostic test for diabetes, but its impact on disease prevalence is unknown. This study evaluated the concordance between HbA1c and fasting plasma ...glucose (FPG) in the diagnosis of diabetes in the general population.
The study was designed as a population based investigation, with participants being sampled from the Ho Chi Minh City, Vietnam. Blood samples were collected after overnight fasting and analyzed within 4 hours after collection. HbA1c was measured with high pressure liquid chromatography (Arkray Adams, Japan). FPG was measured by the hexokinase method (Advia Autoanalyzer; Bayer Diagnostics, Germany). Diabetes was defined as HbA1c ≥ 6.5% or FPG ≥ 7.0 mmol/L. Prediabetes was classified as HbA1c between 5.7% and 6.4%.
The study included 3523 individuals (2356 women) aged 30 years and above. Based on the HbA1c test, the prevalence of diabetes and prediabetes was 9.7% (95%CI, 8.7-10.7%; n = 342) and 34.6% (33.0-36.2; n = 1219), respectively. Based on the FPG test, the prevalence of diabetes and prediabetes was 6.3% (95%CI, 5.5-7.2%; n = 223) and 12.1% (11.1-13.2; n = 427). Among the 427 individuals identified by FPG as "pre-diabetes", 28.6% were classified as diabetes by HbA1c test. The weighted kappa statistic of concordance between HbA1c and FPG was 0.55, with most of the discordance being in the prediabetes group.
These data indicate that there is a significant discordance in the diagnosis of diabetes between FPG and HbA1c measurements, and the discordance could have significant impact on clinical practice. FPG appears to underestimate the burden of undiagnosed diabetes.
This study theoretically reports the comprehensive kinetic mechanism of the aniline + OH reaction in the range of 200–2000 K and 0.76–7600 Torr. The temperature- and pressure-dependent behaviors, ...including time-resolved species profiles and rate coefficients, were studied within the stochastic RRKM-based master equation framework with the reaction energy profile, together with molecular properties of the species involved, characterized at the M06-2X/aug-cc-pVTZ level. Hindered internal rotation and Eckart tunneling treatments were included. The H-abstraction from the −NH2 moiety (to form C6H5NH (P1)) is found to prevail over the OH-addition on the C atom at the ortho site of aniline (to form 6-hydroxy-1-methylcyclohexa-2,4-dien-1-yl (I2)) with the atmospheric rate expressions (in cm3/molecule/s) as k abstraction(P1) = 3.41 × 101 × T –4.56 × exp (−255.2 K/T) for 200–2000 K and k addition(I2) = 3.68 × 109 × T –7.39 × exp (−1163.9 K/T) for 200–800 K. The U-shaped temperature-dependent characteristics and weakly positive pressure dependence at low temperatures (e.g., T ≤ 800 K and P = 760 Torr) of k total(T) are also observed. The disagreement in k total(T) between the previous calculations and experimental studies is also resolved, and atmospheric aniline is found to be primarily removed by OH radicals (τOH ∼ 1.1 h) in the daytime. Also, via TD-DFT simulations, it is recommended to include P1 and I2 in any atmospheric photolysis-related model.
Boronic acids are centrally important functional motifs and synthetic precursors. Visible light-induced borylation may provide access to structurally diverse boronates, but a broadly efficient ...photocatalytic borylation method that can effect borylation of a wide range of substrates, including strong C–O bonds, remains elusive. Herein, we report a general, metal-free visible light-induced photocatalytic borylation platform that enables borylation of electron-rich derivatives of phenols and anilines, chloroarenes, as well as other haloarenes. The reaction exhibits excellent functional group tolerance, as demonstrated by the borylation of a range of structurally complex substrates. Remarkably, the reaction is catalyzed by phenothiazine, a simple organic photocatalyst with MW < 200 that mediates the previously unachievable visible light-induced single electron reduction of phenol derivatives with reduction potentials as negative as approximately – 3 V versus SCE by a proton-coupled electron transfer mechanism. Mechanistic studies point to the crucial role of the photocatalyst–base interaction.
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