Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of statins on biomarkers of bone metabolism: a randomised trial.

BACKGROUND AND AIM Recently, several studies have indicated there may be differences among statins regarding a possible association between therapy and a reduction in risk of fractures. No data from prospective randomised clinical trials designed to assess either biochemical or clinical effects on bone metabolism are yet available. We assayed levels of biochemical markers of bone formation in stored serum samples from a recently completed randomised clinical trial conducted to compare the effects of simvastatin and atorvastatin on the lipid profile of patients with hypercholesterolaemia. METHODS AND RESULTS This 12-week, randomised, multicenter, open-label study was designed to compare the safety and lipid-lowering efficacy of simvastatin 40 mg or 80 mg with that of atorvastatin 20 mg or 40 mg in 846 hypercholesterolaemic patients. Stored serum samples from this study were analysed to compare the effects of simvastatin and atorvastatin on 2 biomarkers of bone turnover, bone-specific alkaline phosphatase (BSAP), a marker of bone formation, and C-teleopeptide of type 1 collagen (CTx), a marker of bone resorption. Treatment with simvastatin 40 and 80 mg/day, but not atorvastatin 20 and 40 mg/day, led to significant (p < 0.05) reductions in BSAP in both men (4.1-5.4% reduction) and women (4.2-7.4% reduction). In addition, there appeared to be a dose-dependent effect with greater reductions in BSAP seen with the 80 mg dose of simvastatin. Treatment with either 20 mg or 40 mg of atorvastatin had no significant effect on BSAP levels on the groups as a whole or in the gender-specific subgroups. CTx showed a small, but not statistically significant, decrease with simvastatin, again with an apparent dose-related trend. Atorvastatin treatment generally resulted in small, non significant increases in CTx. CONCLUSIONS The present serum bone biomarker results show that treatment with simvastatin, but not atorvastatin, decreases BSAP and suggest that simvastatin may have a beneficial effect on bone turnover.
Disentangling the predictive validity of high school grades for academic success in university

To refine selective admission models, we investigate which measure of prior achievement has the best predictive validity for academic success in university. We compare the predictive validity of three core high school subjects to the predictive validity of high school grade point average (GPA) for academic achievement in a liberal arts university programme. Predictive validity is compared between the Dutch pre-university (VWO) and the International Baccalaureate (IB) diploma. Moreover, we study how final GPA is predicted by prior achievement after students complete their first year. Path models were separately run for VWO (n = 314) and IB (n = 113) graduates. For VWO graduates, high school GPA explained more variance than core subject grades in first-year GPA and final GPA. For IB graduates, we found the opposite. Subsequent path models showed that after students’ completion of the first year, final GPA is best predicted by a combination of first-year GPA and high school GPA. Based on our small-scale results, we cautiously challenge the use of high school GPA as the norm for measuring prior achievement. Which measure of prior achievement best predicts academic success in university may depend on the diploma students enter with.
Evidence for a Role of the Cellular ND10 Protein PML in Mediating Intrinsic Immunity against Human Cytomegalovirus Infections

ABSTRACT Several viruses, including human cytomegalovirus (HCMV), encode proteins that colocalize with a cellular subnuclear structure known as ND10. Since only viral DNA deposited at ND10 initiates transcription, ND10 structures were hypothesized to be essential for viral replication. On the other hand, interferon treatment induces an up-regulation of ND10 structures and viruses have evolved polypeptides that disperse the dot-like accumulation of ND10 proteins, suggesting that ND10 could also be part of an intrinsic defense mechanism. In order to obtain evidence for either a proviral or an antiviral function of ND10, we generated primary human fibroblasts with a stable, short interfering RNA-mediated knockdown (kd) of PML. In these cells, other ND10-associated proteins like hDaxx showed a diffuse nuclear distribution. Interestingly, we observed that HCMV infection induced the de novo formation of ND10-like hDaxx and Sp100 accumulations that colocalized with IE2 and were disrupted, in the apparent absence of PML, in an IE1-dependent manner during the first hours after infection. Furthermore, infection of PML-kd cells with wild-type HCMV at a low multiplicity of infection resulted in enhanced replication. In particular, a significantly increased plaque formation was detected, suggesting that more cells are able to support initiation of replication in the absence of PML. While there was no difference in viral DNA uptake between PML-kd and control cells, we observed a considerable increase in the number of immediate-early (IE) protein-positive cells, indicating that the depletion of PML augments the initiation of viral IE gene expression. These results strongly suggest that PML functions as part of an intrinsic immune mechanism against cytomegalovirus infections.
Follow-up of patients with unexplained syncope and inducible ventricular tachyarrhythmias: analysis of the AVID registry and an AVID substudy. Antiarrhythmics Versus Implantable Defibrillators.

INTRODUCTION A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND RESULTS Included in the AVID registry were patients from all participating sites who had "out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms. " In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.
Six-month outcomes of HIV-infected patients given short-course fluconazole therapy for asymptomatic cryptococcal antigenemia

Objective:In HIV-infected adults in sub-Saharan Africa, asymptomatic cryptococcal antigenemia at the time of antiretroviral therapy (ART) initiation is associated with more than 20% increased mortality. Provisional recommendations for treatment of asymptomatic cryptococcal antigenemia are neither well substantiated nor feasible in many resource-poor settings. After hospitals in Tanzania implemented a programme providing serum cryptococcal antigen (CrAg) screening with 4-week intensive fluconazole treatment for CrAg-positive patients, we were asked to assess the impact of this programme on mortality. Design:In this retrospective operational research study, we documented 6-month outcomes of HIV-infected adults who had had CD4+ cell counts less than 200 cells/&mgr;l at the time of starting ART and had been screened for cryptococcal antigenemia over a period of 15 months. Methods:We randomly selected three CrAg-negative patients, matched for ART start date, for every CrAg-positive patient who had been identified and treated with the 4-week intensive fluconazole course. The primary outcome was 6-month mortality in CrAg-positive and CrAg-negative groups. Results:Mortality of CrAg-positive HIV-infected adults who received short-course fluconazole was noninferior to CrAg-negative adults. At 6 months, 16 of 18 CrAg-positive and 46 of 54 CrAg-negative patients were alive [88.9% versus 85.1%, −3.9% absolute difference (one-sided 90% confidence interval +10.8%)]. No deaths in the CrAg-positive group seemed to be due to cryptococcal meningitis. Conclusion:This study suggests that even short-course intensive fluconazole could reduce the mortality of patients with asymptomatic cryptococcal antigenemia. Further studies are needed to confirm if this dose is both optimal for patient survival and feasible for wide implementation in resource-poor settings where mortality of cryptococcal disease is highest.
Dosimetric Response of a REM-500 in Low Energy Neutron Fields Typical of Nuclear Power Plants

AbstractThis study investigates the response of a REM-500 to assess neutron quality factor and dose equivalent in low energy neutron fields, which are commonly encountered in the workplace environment of nuclear power stations. The McMaster University 3 MV Van de Graaff accelerator facility was used to measure the response of the instrument in monoenergetic neutron fields in the energy range 51 to 727 keV by bombarding a thin LiF target with 1.93–2.50 MeV protons. The energy distribution of the neutron fields produced in the facility was measured by a 3He filled gas ionization chamber. The MCA mode of the REM-500 instrument was used to collect lineal energy distributions at varying neutron energies and to calculate the frequency and dose-mean lineal energies. The effective quality factor, Q¯, was also calculated using the values of Q(y) listed in the REM-500 operation manual and compared with those of ICRP 60. The authors observed a continuously increasing trend in y¯F, y¯D, and Q¯ with an increase in neutron energy. It is interesting to note that standard tissue equivalent proportional counters (TEPCs) filled with tissue equivalent (TE) gas give rise to a similar trend for these microdosimetric quantities of interest in the same energy range; however, the averages calculated in this study are larger by about 15% compared to a TEPC filled with propane-based TE gas probably because of the larger stopping power of protons in propane compared to TE gas. These somewhat larger event sizes did not result in any significant increase in the Q¯ compared to those obtained from a TEPC filled with TE gas and were found to be in good agreement with other measurements reported earlier at corresponding neutron energies. The instrument quality factor response, RQ, defined as the ratio of measured quality factor to the calculated quality factor in an ICRU tissue sphere, was found to vary with neutron energy. The instrument response, RQ, was ∼ 0.6 at 727 keV, which deteriorates further to ∼0.3 at 51 keV neutron energy. The counter response based on ICRP 60 was comparable to an ideal response of 1.0 above 600 keV, which dropped to ∼0.8 at 159 keV and ∼0.4 at 51 keV neutron energy. The decline in counter quality factor response based on ICRP 60 was found to be much steeper than that when using the instrument’s built-in function for quality factor. The REM-500 measures a dose equivalent at 727 keV, which is 60% of the ambient dose equivalent, 40% at 159 keV, and 15% at 51 keV. Two algorithms have been developed, one for real time measurement and another to be used post-measurement, and their efficacy is demonstrated in determining the quality factor and the ambient dose equivalent in low energy neutron fields, which are typical for the workplace environment in CANDU® nuclear power generating stations.
Role of High Resolution Sonography in Differentiating Benign and Malignant Nodules of Thyroid

Thyroid nodules are extremely common. It found in 4–8% of adults by population, 10–41% by ultrasound, and 50% at autopsy. High resolution ultrasound is the primary imaging modality for the evaluation of these nodules. 150 patients with thyroid nodules were taken in our study. 11 were males and 139 were females approximately 189 nodules were detected sono graphically in 150 patient. Nodules less than 1cm and purely cystic lesion were excluded from our study. Most of the FNAC were performed under USG guidance and histo-pathological findings were considered as final diagnosis. Cystic lesions were found to be benign. Hyper echoic & round shape lesions were found to be benign. Calcified lesions have more chance of malignancy. 22.1% calcified lesion were found in benign lesions. Calcified lesions are further divided into micro & macro according to their sizes. Micro calcified lesions were found to be malignant lesion (approx. 83 %). To summarize, gray scale USG findings of thyroid nodules were helpful in identifying clinically significant nodules and to differentiate between malignant and benign nodules. Our study revealed, the malignant features of poorly defined margins, micro calcification, marked hypo echogenicity and cystic predominance nature were found to have high diagnostic accuracy for the identification of malignant thyroid nodules while benign lesions demonstrated solid consistency, well defined margins and regular halo.
Experimental Measurement of Two-Phase Relative Permeabilities in Synthetic Vertical Fractures

Relative permeability characteristics in porous media have been studied extensively and are reasonably well understood. However there have been comparatively few studies of relative permeability in fractures. Given that geothermal reservoir permeabilities are almost always dominated by fractures, understanding of fracture relative permeabilities is essential for accurate geothermal reservoir simulation. Two-phase fracture flow was simulated using an artificial fracture created between an aluminum plate and a sheet of glass. The experiments simulated horizontal flow in a vertical fracture to compare with the work of Chen (2005) who made similar measurements on the same apparatus oriented horizontally. N2-water, steam-water, and CO2-water relative permeabilities were measured using both smooth and rough glass. Measured relative permeabilities were compared with the work of Chen and with known relative permeability models.
The maximum congested cut problem and its robust counterpart: Exact and approximation algorithms for the single and the multicommodity case

We study an optimization problem which can be interesting in several network applications, especially in telecommunication. Given a capacitated directed network G in which a flow, related to a certain commodity, has to be sent from a given set of origins to a given set of destinations, we want to compute a maximum congested cut, i.e., a cut (S,T) of G which maximizes the ratio between the net demand of T and the capacity of the cut. We will show that a maximum congested cut can be computed in polynomial time by formulating the problem as a special maximum mean‐weight cut problem, and solving it by Newton's method for linear fractional combinatorial optimization (Radzik, Complexity in Numerical Optimization, World Scientific, Singapore, 1993). The introduced formulation will be extended to the case in which the flow demands vary in a polyhedron D, and a cut has to be determined which maximizes the congestion with respect to the flow demands in D, addressing a robust version of the problem. We will prove that the robust maximum congested cut problem is coNP‐Hard. Special cases solvable in polynomial time as well as approximation algorithms for some relevant hard cases will be proposed. The specialization of the proposed approaches to the well‐studied class of Hose models (Duffield et al., Proc., Conf Appl Technol Architect Protocol Comp Comm 29 (1999), 95–108) will be discussed. Then, in the second part of the paper, we will investigate the case in which k commodities are given, and a maximum congested cut has to be computed in such a multicommodity flow context. This problem is NP‐Hard. Some algorithmic considerations will be formulated in order to approximate the maximum congested cut in multicommodity networks, also addressing the robust version of the problem. A consequence of the stated results is a polynomial time algorithm for the sparsest cut problem in undirected graphs, for the special case in which k is O(log n), and an O(${{k}\over{\log n}}$)‐approximationalgorithm for the general case, where n denotes the cardinality of the node set. Furthermore, a new heuristic approach for the directed sparsest cut problem will be suggested. © 2007 Wiley Periodicals, Inc. NETWORKS, 2008
Evolving Therapeutic Strategies to Improve Nonsteroidal Anti-inflammatory Drug Safety

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess potent anti-inflammatory and analgesic properties through inhibition of cyclooxygenase enzymes (COX-1 and COX-2), which are responsible for synthesis of proinflammatory mediators. NSAIDs are frequently used for treatment of acute and chronic pain conditions. However, their use is associated with serious dose-dependent gastrointestinal (GI), cardiovascular, renal, and hepatic adverse effects, which pose a serious clinical concern for both patients and physicians. During the past 2 decades, approaches to improving the tolerability of NSAIDs were mainly directed toward discovery of COX-2 selective NSAIDs (coxibs), which were expected to minimize the risk of GI injury. Unfortunately, the results from multiple clinical studies have shown that treatment with coxibs may increase the risk for cardiovascular complications. This review summarizes current strategies used to reduce the toxicity of NSAIDs and outlines novel therapeutic approaches still in preclinical development. To minimize the risk of GI ulcerations and bleeding, combination therapies with gastroprotective agents are currently recommended. The new therapeutic agents anticipated to have similar effects include nitric oxide– and hydrogen sulfide–releasing NSAIDs. Novel manufacturing technologies enhance dissolution and absorption of NSAID products, allowing for their administration at low doses, which could lead to improved drug tolerability without diminishing the analgesic and anti-inflammatory efficacy of NSAIDs. This principle is in line with the current recommendation by the US Food and Drug Administration that NSAIDs should be used at the lowest effective dosage. Finally, NSAID formulations targeted directly to the site of inflammation are expected to reduce systemic drug exposure and thus decrease the risk of systemic adverse effects.
Epidemiologic differences between the two varieties of Cryptococcus neoformans.

This report of the worldwide distribution of two varieties of Cryptococcus neoformans was drawn from data on 628 clinical isolates and from data on 97 additional isolates from other laboratories. Tests showed that 100% of the cultures from Austria, Belgium, Denmark, France, Germany, Holland, Italy, Switzerland, and Japan belonged to C. neoformans var. neoformans. More than 85% of the isolates from Argentina, Canada, the United Kingdom, and the United States (except southern California) were of C. neoformans var. neoformans, the remainder being of C. neoformans var. gattii . There was an unusually high prevalence (35-100%) of C. neoformans var. gattii in Australia, Brazil, Cambodia, Hawaii, southern California, Mexico, Paraguay, Thailand, Vietnam, Nepal, and countries in central Africa. These findings indicated that C. neoformans var. gattii is prevalent only in tropical and subtropical regions. Seventy per cent of the total isolates studied were of serotype A of C. neoformans var. neoformans. Serotype D (9% of the total) was common in Europe, but was found infrequently in other regions. Among the two serotypes of C. neoformans var. gattii , serotype B was 4.5 times more prevalent than serotype C. The majority (88%) of type C isolates in our collection were from southern California.
Citation: Almoosawi, Suzana, Palla, Luigi, Walshe, Ian, Vingeliene, Snieguole and Ellis, Jason (2018) Long Sleep Duration and Social Jetlag Are Associated Inversely with a Healthy Dietary Pattern in Adults: Results from the UK National Diet and Nutrition Survey Rolling

Limited observational studies have described the relationship between sleep duration and overall diet. The present study investigated the association between sleep duration on weekdays or social jetlag and empirically derived dietary patterns in a nationally representative sample of UK adults, aged 19–64 years old, participating in the 2008–2012 UK National Diet and Nutrition Survey Rolling Programme. Survey members completed between three to four days of dietary records. Sleep duration on weekdays was categorized into tertiles to reflect short, normal, and long sleep duration. Social jetlag was calculated as the difference between sleep duration on weekends and weekdays. The association between sleep duration/social jetlag and dietary patterns, derived by principal components analysis, was assessed by regressing diet on sleep, whilst accounting for the complex survey design and adjusting for relevant confounders. Survey members in the highest tertile of sleep duration had on average a 0.45 (95% Confidence Interval (CI) −0.78, −0.12) lower healthy dietary pattern score, compared to middle tertile (p = 0.007). There was an inverted u-shaped association between social jetlag and the healthy dietary pattern, such that when sleep on weekends exceeded weekday sleep by 1 h 45 min, scores for indicating a healthy dietary pattern declined (p = 0.005). In conclusion, long sleep duration on weekdays and an increased social jetlag are associated with a lower healthy dietary pattern score. Further research is required to address factors influencing dietary patterns in long sleepers.