Exclusive B→(K∗,ρ)γB \to (K^*, \rho) \gamma decays in the general two-Higgs-doublet models

By employing the QCD factorization approach, we calculated the next-to-leading order new physics contributions to the branching ratios, CP asymmetries, isospin and U-spin symmetry breaking of the exclusive decays $B \to V \gamma$ ($V=K^*, \rho$), induced by the charged Higgs penguins in the general two-Higgs-doublet models. Within the considered parameter space, we found that (a) the new physics corrections to the observables are generally small in the model I and model III-A, moderate in model II, but large in model III-B; (b) from the well measured branching ratios and upper limits, a lower bound of \mhp > 200 GeV in model II was obtained, while the allowed range of \mhp in model III-B is 226 \leq \mhp \leq 293 GeV; these bounds are comparable with those from the inclusive $B \to X_s \gamma$ decay; (c)the NLO Wilson coefficient $C_7(m_b)$ in model III-B is positive and disfavered by the measured value of isospin symmetry breaking $\Delta_{0-}^{exp} (K^*\gamma) = (3.9 \pm 4.8)$, but still can not be excluded if we take the large errors into account; (d) the CP asymmetry \acp(B \to \rho \gamma) in model III-B has an opposite sign with the one in the standard model (SM), which may be used as a good observable to distinguish the SM from model III-B; (e) the isospin symmetry breaking $\Delta(\rho\gamma)$ is less than 10% in the region of $\gamma = [ 40 \sim 70]^\circ$ preferred by the global fit result, but can be as large as 20 to 40% in the regions of $\gamma \leq 10^\circ$ and $\gamma \geq 120^\circ$. The SM and model III-B predictions for $\Delta(\rho \gamma)$ are opposite in sign for small or large values of the CKM angles; (f) the U-spin symmetry breaking $\Delta U(K^*,\rho)$ in the SM and the general two-Higgs-doublet models is generally small in size: $\sim 10^{-7}$.Comment: Revtex, 38 pages with 14 eps figures, minor correction

Long-term therapy with trandolapril, a new nonsulfhydryl ACE inhibitor, in hypertension : a multicenter international trial

An international trial recruited 1,049 patients from 122 investigators. After a 2- to 4-week, single-blind placebo run-in, patients were treated unblinded for 1 year. Therapy was started with trandolapril 2 mg once daily. The dose was increased to 4 mg/day if, after 1 month, blood pressure was not normalized, and then was combined with diuretics and/or calcium antagonists in increasing doses if necessary. At the cutoff point for this interim analysis, 481 patients had been treated for over 12 months and 960 for 3 months. At end point, trandolapril produced a significant decrease in blood pressure (-14 mm Hg for mean supine diastolic blood pressure). Blood pressure was normalized in 60% of the population with monotherapy. Trandolapril, alone or in combination with diuretics or calcium antagonists, was well tolerated clinically and biochemically. Only 3.9% patients reported dry cough. Withdrawals of patients from the study for treatment related reasons were 3.8%. Trandolapril had also an excellent antihypertensive effect and was well tolerated in elderly patients, in patients with glucose intolerance, and in patients with renal dysfunction

Risk factors for ductal and lobular breast cancer: results from the nurses' health study

Introduction Ductal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses\u27 Health Study. Methods Multivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes. Results The associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het \u3c 0.001) and postmenopausal hormone use (P-het \u3c 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het ≥ 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors. Conclusions These data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology

Brokering innovation to better leverage R&D investment

What is the contribution of innovation brokers in leveraging research and development (R&D) investment to enhance industry-wide capabilities? The case of the Australian Cooperative Research Centre for Construction Innovation (CRC CI) is considered in the context of motivating supply chain firms to improve their organizational capabilities in order to acquire, assimilate, transfer and exploit R&D outcomes to their advantage, and to create broader industry and national benefits. A previous audit and analysis has shown an increase in business R&D investment since 2001. The role of the CRC CI in contributing to growth in the absorptive capacity of the Australian construction industry as a whole is illustrated through two programmes: digital modelling/building information modelling (BIM) and construction site safety. Numerous positive outcomes in productivity, quality, improved safety and competitiveness were achieved between 2001 and 2009

Renal Impairment and Cardiovascular Disease in HIV-positive Individuals; The D:A:D Study

BACKGROUND: While the association between renal impairment and cardiovascular disease (CVD) is well established in the general population, the association remains poorly understood in HIV-positive individuals. METHODS: Individuals with >2 estimated glomerular filtration rate (eGFRs) after 1/2/2004 were followed until CVD, death, last visit plus six months or 1/2/2015. CVD was defined as centrally validated myocardial infarction, stroke, invasive cardiovascular procedures or sudden cardiac death. RESULTS: During 8.0 years median follow-up (Interquartile range 5.4-8.9) 1,357 of 35,357 developed CVD (incidence 5.2/1000 person-years [95%confidence interval, CI [5.0-5.5]). Confirmed baseline eGFR and CVD were closely related with 1.8% [95%CI 1.6-2.0%] estimated to develop CVD at five years at eGFR>90 ml/min/1.73m(2), increasing to 21.1% [95%CI 6.6-35.6%] at eGFR<30 ml/min/1.73m(2) The strong univariate relationship between low current eGFR and CVD was primarily explained by increasing age in adjusted analyses, although all eGFRs<80 ml/min/1.73m(2) remained associated with 30-40% increased CVD rates and particular high rates at eGFR<30 ml/min/1.73m(2) (3.08 [95%CI 2.04-4.65]). CONCLUSIONS: Among HIV-positive individuals in a large contemporary cohort a strong relation between confirmed impaired eGFR and CVD was observed. This finding highlights the need for renal preventive measures and intensified monitoring for emerging CVD, in particular in older individuals with continuously low eGFR

Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study

INTRODUCTION: Breast cancers of different histology have different clinical and prognostic features. There are also indications of differences in aetiology. We therefore evaluated the risk of the three most common histological subtypes in relation to menopausal hormone therapy and other breast cancer risk factors. METHODS: We used a population-based case-control study of breast cancer to evaluate menopausal hormone therapy and other breast cancer risk factors for risk by histological subtype. Women aged 50 to 74 years, diagnosed with invasive ductal (n = 1,888), lobular (n = 308) or tubular (n = 93) breast cancer in Sweden in 1993 to 1995 were compared with 3,065 age-frequency matched controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ductal, lobular, and tubular cancer. RESULTS: Women who had used medium potency estrogen alone were at increased risks of both ductal and lobular cancer. Medium potency estrogen-progestin was associated with increased risks for all subtypes, but the estimates for lobular and tubular cancer were higher compared with ductal cancer. We found OR 5.6 (95% CI 3.2–9.7) for lobular cancer, OR 6.5 (95% CI 2.8–14.9) for tubular cancer and OR 2.3 (95% CI 1.6–3.3) for ductal cancer with ≥5 years use of medium potency estrogen-progestin therapy. Low potency oral estrogen (mainly estriol) appeared to be associated with an increased risk for lobular cancer, but the association was strongest for short-term use. Reproductive and anthropometric factors, smoking, and past use of oral contraceptives were mostly similarly related to the risks of the three breast cancer subtypes. Recent alcohol consumption of > 10 g alcohol/day was associated with increased risk only for tubular cancer (OR 3.1, 95% CI 1.4–6.8). CONCLUSION: Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer. We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer

At-admission prediction of mortality and pulmonary embolism in an international cohort of hospitalised patients with COVID-19 using statistical and machine learning methods

By September 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism (PE) in COVID-19 patients as one of the most severe preventable complications of COVID-19. Early recognition can help provide life-saving targeted anti-coagulation therapy right at admission. Using a dataset of more than 800,000 COVID-19 patients from an international cohort, we propose a cost-sensitive gradient-boosted machine learning model that predicts occurrence of PE and death at admission. Logistic regression, Cox proportional hazards models, and Shapley values were used to identify key predictors for PE and death. Our prediction model had a test AUROC of 75.9% and 74.2%, and sensitivities of 67.5% and 72.7% for PE and all-cause mortality respectively on a highly diverse and held-out test set. The PE prediction model was also evaluated on patients in UK and Spain separately with test results of 74.5% AUROC, 63.5% sensitivity and 78.9% AUROC, 95.7% sensitivity. Age, sex, region of admission, comorbidities (chronic cardiac and pulmonary disease, dementia, diabetes, hypertension, cancer, obesity, smoking), and symptoms (any, confusion, chest pain, fatigue, headache, fever, muscle or joint pain, shortness of breath) were the most important clinical predictors at admission. Age, overall presence of symptoms, shortness of breath, and hypertension were found to be key predictors for PE using our extreme gradient boosted model. This analysis based on the, until now, largest global dataset for this set of problems can inform hospital prioritisation policy and guide long term clinical research and decision-making for COVID-19 patients globally. Our machine learning model developed from an international cohort can serve to better regulate hospital risk prioritisation of at-risk patients

Effect of Changes in Body Mass Index on the Risk of Cardiovascular Disease and Diabetes Mellitus in HIV-Positive Individuals: Results From the D:A:D Study

BACKGROUND: Weight gain is common among people with HIV once antiretroviral treatment (ART) is commenced. We assess the effect of changes in body mass index (BMI), from different baseline BMI levels, on the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). METHODS: D:A:D participants receiving ART were followed from their first BMI measurement to the first of either CVD or DM event, or earliest of 1/2/2016 or 6 months after last follow-up. Participants were stratified according to their baseline BMI, and changes from baseline BMI were calculated for each participant. Poisson regression models were used to assess the effects of changes on BMI on CVD or DM events. RESULTS: There were 2,104 CVD and 1,583 DM events over 365,287 and 354,898 person years (rate: CVD 5.8/1000 (95% CI 5.5-6.0); DM 4.5/1000 (95% CI 4.2 - 4.7)). Participants were largely male (74%), baseline mean age of 40 years and median BMI of 23.0 (IQR: 21.0-25.3). Risk of CVD by change in BMI from baseline, stratified by baseline BMI strata showed little evidence of an increased risk of CVD with an increased BMI in any baseline BMI strata. An increase in BMI was associated with an increased risk of DM across all baseline BMI strata. CONCLUSIONS: While increases in BMI across all levels of baseline BMI were not associated with an increased risk of CVD, such changes were consistently associated with increased risk of DM. There was also some evidence of an increased risk of CVD with a decrease in BMI

Reproductive factors and specific histological types of breast cancer: prospective study and meta-analysis

Little is known about how reproductive factors affect the risk of breast cancers of different histology. In an analysis of prospective data on 1.2 million middle-aged UK women, we used proportional hazards models to estimate the relative risks of six histological types in relation to menarche, childbearing and menopause. During 8.7 million person-years of follow-up, 17 923 ductal, 3332 lobular, 1062 tubular, 944 mixed ductal lobular, 330 mucinous and 117 medullary cancers were diagnosed. The effect of both age at menarche and age at first birth was greatest for lobular tumours; relative risks per 5-year increase in age at menarche for ductal, lobular, and tubular cancers were 0.93 (0.87–0.99), 0.65 (0.56–0.76), and 0.75 (0.57–0.98), respectively (P-value for heterogeneity=0.0001); and the relative risks per 5-year increase in age at first birth were 1.10 (1.07–1.12), 1.23 (1.17–1.29), and 1.13 (1.03–1.23), respectively (P-value for heterogeneity=0.0006). Increasing parity reduced the risk of each tumour type, except medullary cancers, but the reduction in risk was greater for mucinous cancers than for any other subtype considered (P<0.05 for comparison with each other subtype in turn). The effect of menopause did not vary significantly by tumour histology. Meta-analysis of published results on the effects of age at menarche and age at first birth on ductal and lobular cancers were in keeping with our findings

A Comparative Study of Defeasible Argumentation and Non-monotonic Fuzzy Reasoning for Elderly Survival Prediction Using Biomarkers

Computational argumentation has been gaining momentum as a solid theoretical research discipline for inference under uncertainty with incomplete and contradicting knowledge. However, its practical counterpart is underdeveloped, with a lack of studies focused on the investigation of its impact in real-world settings and with real knowledge. In this study, computational argumentation is compared against non-monotonic fuzzy reasoning and evaluated in the domain of biological markers for the prediction of mortality in an elderly population. Different non-monotonic argument-based models and fuzzy reasoning models have been designed using an extensive knowledge base gathered from an expert in the field. An analysis of the true positive and false positive rate of the inferences of such models has been performed. Findings indicate a superior inferential capacity of the designed argument-based models