Miracle-dz/UniFAR-FTUs huggingface dataset:
The Genetic Background of Metabolic Trait Clusters in Children and Adolescents.

BACKGROUND It is well known that metabolic risk factors of cardiovascular diseases are correlated, but the background of this clustering in children is more poorly known than in adults. Thus, we studied the contribution of genetic and environmental factors to the clustering of metabolic traits in childhood and adolescence. DATA AND METHODS Nine metabolic traits were measured in 214 complete twin pairs aged 3-18 years in the Autonomous Region of Madeira, Portugal, in 2007 and 2008. The variation of and covariations between the traits were decomposed into genetic and environmental components by using classical genetic twin modeling. RESULTS A model, including additive genetic and environmental factors unique for each twin individual, explained the variation of metabolic factors well. Under this model, the heritability estimates varied from 0.47 (systolic blood pressure in children under 12 years of age) to 0.91 (high-density lipoprotein [HDL] cholesterol in adolescents 12 years of age or older). The most systematic correlations were found between adiposity (body mass index and waist circumference) and blood lipids (HDL cholesterol, low-density lipoprotein cholesterol, and triglycerides), as well as blood pressure. These correlations were mainly explained by common genetic factors. CONCLUSIONS Our results suggest that obesity, in particular, is behind the clustering of metabolic factors in children and adolescents. Both general and abdominal obesity partly share the same genetic background as blood lipids and blood pressure. Obesity prevention early in childhood is important in reducing the risk of metabolic diseases in adulthood.
Brain Network Modularity Predicts Exercise-Related Executive Function Gains in Older Adults

Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that, especially in low-performing individuals, global network properties can capture individual differences in neuroplasticity.
Symptomatic presentation of early colorectal cancer.

INTRODUCTION It is believed that increased detection of earlier stage colorectal cancer can only be achieved by screening asymptomatic individuals. We describe a referral pathway for a symptomatic population which achieves a 30% Dukes' A detection rate. PATIENTS AND METHODS From October 1999, 4253 patients with distal colonic symptoms, referred by general practitioners, completed a patient consultation questionnaire (PCQ) linked to a computerised record. A weighted numerical score (WNS) was derived for each patient. Patients underwent flexible sigmoidoscopy, a diagnostic outcome was recorded and later Dukes' stage appended. Early and advanced colorectal cancers were separated and PCQ derived symptom profiles compared. Chi-square, Fisher exact, Student's t-test and logistic regression were used for statistical analysis. RESULTS A total of 183 patients had cancer, 55 (30%) were Dukes' A early colorectal cancers, 112 were advanced colorectal cancers (Dukes' B-D) and 16 could not be staged. Early colorectal cancers had significant symptoms and comparable profile to advanced colorectal cancers. The tendency in advanced colorectal cancers was towards greater symptom prevalence for only a few primary and systemic symptoms, as reflected by a higher WNS of 75 (P = 0.001). CONCLUSIONS Early colorectal cancers do have significant symptoms which can easily be captured by a PCQ and objective scoring tool in the secondary care setting. Detection of these cancers has the potential to improve survival.
The numerical modelling and experimental validation of a partial discharge within an air-filled cavity bound in oil impregnated paper

A numerical model to simulate a partial discharge within a bound cavity is presented in this paper. The partial discharge inception voltage and current pulse characteristics are established numerically and compared against experimental tests. The defect geometry used in this work is associated with a high voltage transformer bushing, namely a cavity formed between a punctured aluminium grading foil layer and the surrounding oil impregnated paper insulation. In the simulations, hydrodynamic drift-diffusion formulation is used to transport electron, positive and negative ion concentrations under the influence of an electric field; the movement of species is translated into an external current pulse. Experimentally, a high speed oscilloscope is used to capture the current pulse during a discharge. The numerical technique, defect sample preparation and high voltage laboratory setup, are discussed in detail. The results show a good agreement between numerical and experimental methods.
Structural models of Na+, Ca2+, and K+ channels.

The structure determination of voltage-gated channels by the combination of molecular modeling and mutagenesis experiments is a long term, iterative process. As such, the models should be considered as a work in progress, with changes expected as more data becomes available. The primary role of the models is that they assimilate the known data and provide ideas for further experiments to elucidate the real structures. Although the models presented here have already gone through two or three cycles of development and testing, many aspects remain tentative. Perhaps the most significant result so far is that the P segment was experimentally confirmed to form the ion-selective part of the channel. In a subsequent cycle of testing and modeling, the specific residues responsibility for Na+ and Ca2+ selectivity have been identified and the selectivity filter of K+ channels is now predicted to be formed by the side chains, but rather by the carbonyl oxygens of the conserved Gly-Tyr-Gly sequence backbone. As another example, the 9p residue of the P segment of K+ channels was originally modeled as either being buried in the protein or accessible channels was originally modeled as either being buried in the protein or accessible from inside the cell only. However, once mutation of this residue to histidine was found to affect blockade by extracellular TEA, protons, Zn2+ and histidine reagents (DeBiasi et al., 1993), the models were updated to have this and the hydrophilic residues in the first part of P form a helix that comprises part of the extracellular, outer vestibular of the pore. While this motif was used also for Na+ and Ca2+ pore models (see Fig. 2) where the putative helices are amphipathic, it remains to be verified. Modeling of the size and shape of the outer vestibule of K+ channels was also aided by the data for the binding of CTX in the extracellular entrance to the pore. Similarly, experiments with peptide toxins such as mu and omega conotoxins may prove useful in modeling the outer vestibules of the Na+ and/or Ca2+ channels. While important advances have been made, it is important to realize that these approaches are still very new. In the future we are likely to see improvements on both the theoretical and experimental sides which will greatly advance the process. (ABSTRACT TRUNCATED AT 400 WORDS)
Water Extracts of Helicobacter pylori Delay Healing of Chronic Gastric Ulcers in Rats: Role of Cytokines and Gastrin-Somatostatin Link

Background: Helicobacter pylori (Hp) is considered as a major risk factor of peptic ulcer, but the pathogenic mechanism of its action has not been fully explained. Aims: This study was designed: (1) to compare the ulcer healing effects of water extract (WE) obtained from type-I cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) expressing Hp and from type-II CagA- and VacA-negative Hp strain with those of vehicle (saline), and (2) to determine the alterations in gastric secretion, gastric blood flow (GBF) and expression of Hp-related cytokines during the ulcer healing in rats treated with toxigenic (type-I) and non-toxigenic (type-II) Hp-derived WE. Methods: Gastric ulcers were produced by serosal application of acetic acid in rats with or without gastric fistula treated with vehicle (saline) or WE originating from type-I or type-II Hp administered intragastrically on days 1, 3, 5 and 7 upon ulcer induction. On days 3, 9 and 15, animals were lightly anesthetized with ether, the abdomen was opened and the GBF was measured by the H2-gas clearance technique in the ulcer area and non-ulcerated mucosa. Venous blood was withdrawn for the measurement of plasma cytokine (IL-1β and TNFα) levels and plasma and gastric contents were also collected for gastrin and somatostatin determination by specific radioimmunoassay. Results: Gastric ulcers healed gradually in vehicle-treated controls and the ulcer area on days 3, 9 and 15 was reduced by 12, 43 and 92%, respectively. In rats treated with WE of type-I Hp, ulcer healing was significantly delayed, and gastritis and infiltration of ulcerated gastric mucosa with inflammatory cells were observed histologically. The prolongation of ulcer healing by WE of both Hp strains was accompanied by a marked fall in the GBF at the ulcer margin and transient hyposecretion especially in rats given WE of type-I Hp strain. On day 15 of ulcer healing, the plasma concentration of IL-1β and TNFα was negligible in vehicle control rats, but it was significantly elevated particularly in rats treated with WE of type-I Hp. RT-PCR analysis revealed that mucosal expression of IL-1β and TNFα mRNA was significantly upregulated in the gastric mucosa of rats treated with either toxigenic or non-toxigenic Hp WE. The plasma gastrin level was significantly higher and the luminal concentration of somatostatin was significantly lower in rats treated with Hp-WE than in vehicle-treated controls and these alterations were more pronounced in rats treated with WE type-I than type-II Hp. Conclusions: WE of toxigenic Hp strain delays ulcer healing due to the reduction in the gastric microcirculation at the ulcer margin, the overexpression of inflammatory cytokines and the impairment of the gastrin-somatostatin link.
Financiamiento de la vivienda en Chile

Tomando como punto de partida un diagnóstico preliminar sobre la problemática y el grado de profundidad alcanzado por el financiamiento de vivienda en Chile, y sobre la base de entrevistas y una encuesta a actores principales del mercado, el presente documento analiza la evolución y situación actual del financiamiento de vivienda. El análisis se focaliza en factores clave relacionados con el funcionamiento de los mercados financieros, la regulación financiera y el marco legal, los aspectos institucionales, y las características del mercado de alquileres. El trabajo se refiere especialmente a temas de particular interés, tales como la utilización de bonos hipotecarios y la securitización, el papel de la regulación prudencial, la importancia de la unidad de fomento, la política de subsidios, y el papel de la banca pública. Se exploran los desafíos futuros del financiamiento de vivienda y se presentan recomendaciones de política. Asimismo, se identifica un conjunto de lecciones aprendidas que pueden ser de utilidad tanto para Chile como para otros países de América Latina y el Caribe. Este estudio forma parte de una iniciativa de investigación más amplia que el Banco ha estado encarando con el propósito de respaldar el desarrollo del financiamiento a la vivienda. La iniciativa incluye una serie de estudios temáticos y de diagnóstico encarados para una muestra representativa de países de la región.
Medicine utilization review at a university teaching hospital in New Delhi

Objective: A prospective medicine usage evaluation based on prescription monitoring was conducted in the medicine OPD of our university teaching hospital to know prescribing trends of different categories of medicines. Materials and Methods: A total of 600 patients were included in the study comprising of 339 (56.5%) males and 261 (43.5%) females. The data were recorded within the OPD by a registered pharmacist on a medicine usage evaluation form, approved by The University Institutional Review Board (IRB). Results: A total of 2365 medicines were prescribed to 600 patients during the 3 months study period. The mean number of medicines per prescription were found to be 3.94. Medicines were most frequently prescribed as solid dosage forms (85.62%), especially tablets (70.82%), and liquid formulations (14.12%). Oral route (96.17%) was the most preferred mode of administration, followed by topical (2.11%) and parenteral (1.60%) routes. Combination therapy (94.33%) was more prevalent than monotherapy (5.66%). An overwhelming tendency for prescribing medicines by brand names (99%) was observed by the physicians. The most frequently prescribed class of medicines were antimicrobials > analgesics > cardiovascular > gastrointestinal agents. The most prescribed individual medicines among various therapeutic classes included isoniazid (antimicrobial), amlodipine (cardiovascular), metformin (hypoglycemic), cetirizine (antiallergic), rabeprazole (GI medicine), atorvastatin (hypolipidemic), dextromethorphan (respiratory medicine), alprazolam (sedative-hypnotic), paracetamol (analgesic). Conclusions: There is a considerable scope of improvement in the existing prescribing practice, especially prescribing by generic names, needs to be encouraged and a hospital formulary has to be developed for the purpose. The number of medicines to be included per prescription should be judged rationally and polypharmacy ought to be curbed. Use of antimicrobial also needs to be rationalized as over usage of antibiotics may lead to the problems such as medicine resistance and noncompliance.
Short-term randomized proof-of-principle trial of TMC278 in patients with HIV type-1 who have previously failed antiretroviral therapy

Background In vitro, TMC278, an investigational next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), has shown activity against wild-type and NNRTI-resistant HIV type-1 (HIV-1) and a higher genetic barrier to the development of resistance than efavirenz or nevirapine. This Phase II open-label trial evaluated the short-term (7-day) antiviral activity of TMC278 administered at three different doses replacing either the protease inhibitor (PI) or NNRTI of an ongoing failing treatment regimen in HIV-1-infected patients. Methods A total of 36 patients on failing antiretroviral therapy containing either an NNRTI or a PI (with evidence of ≥1 NNRTI resistance-associated mutation at screening for the PI group) and plasma viral load (VL)>1,000 copies/ml were randomized to one of three once-daily TMC278 doses (25 mg, 50 mg or 150 mg) for 7 days, while continuing NRTIs used at screening. The primary efficacy parameter was the change on day 8 in log10 plasma VL from baseline. Results On day 8, median (min, max) changes from baseline in plasma VL were -0.87 (-2.3, 0.0), -0.95 (-1.8, 0.4) and -0.66 (-1.3, -0.2) log10 copies/ml for the 25 mg, 50 mg and 150 mg once-daily TMC278 groups, respectively (P<0.001–<0.01). Overall, the median change from baseline was -1.19 log10 copies/ml in the PI-substituted therapy group and -0.71 log10 copies/ml in the NNRTI-substituted therapy group. TMC278 was generally safe and well tolerated with no apparent differences in safety among the three dose groups. Conclusions Once-daily TMC278 showed significant antiviral activity against HIV-1 in treatment-experienced patients with NNRTI failure and/or resistance, and was generally safe and well tolerated.
Women's Self-determination in Cooperative Tourism Microenterprises

The purpose of this study is to better understand how cooperative forms of microentrepreneurship influence women's self-determination. Utilizing the framework of self-determination theory, this study employed a multiple case study approach that involved in-depth interviews, content analysis, field notes, and direct observations. Findings indicate that livelihood opportunities afforded under cooperative tourism microentrepreneurship offer women increased levels of self-determination, but that economic improvements alone are not sufficient in enhancing overall well-being. This study provides a detailed account of the strategies indigenous women employ to enhance their self-determination under cooperative tourism microentrepreneurship models. The results of this study suggest that programs by governments and NGOs should consider non-individual benefits when they engage with communities in tourism planning initiatives. Additionally, interventions aimed at women must also engage men or women may suffer from tensions at home. Finally, this study indicates that simply offering access to credit does not foster self-reliant development. The structures of cooperative models determine outcomes. Therefore, whenever possible, microentrepreneurship models should be designed to enhance strong cooperative social structures
Promoting Our Students: Examining the Role of School Leadership in the Self-Advocacy of At-Risk Students

The purpose of this research is to describe how an alternative school leader taught at-risk students and their parents to advocate for students’ educational interests and how this affected students’ academic and social success. In social justice leadership literature, parents and students are described as passive recipients of a strong social justice leader. But the process described in this research, which is referred to here as self-advocacy, demonstrates a way that principals can include stakeholders (i.e., parents and students) in the struggle for school inclusion and social justice. The study was a 2-year ethnographic study that closely examined the students, parents, staff, community members, and principal of an urban alternative high school. The findings suggest that principals can develop students and parents into self-advocates, who can themselves advocate for students’ school inclusion.
Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis.

BACKGROUND Low-molecular-weight heparins are frequently used to treat venous thromboembolism, but optimal dosing regimens and clinical outcomes need further definition. METHODS In this multicenter, open-label study with blinded adjudication of end points, we randomly assigned patients with acute deep-vein thrombosis to one of three treatment regimens: intravenous administration of unfractionated heparin; subcutaneous administration of a low-molecular-weight heparin, reviparin, twice a day for one week; or subcutaneous administration of reviparin once a day for four weeks. The primary end point was evidence of regression of the thrombus on venography on day 21; secondary end points were recurrent venous thromboembolism, major bleeding within 90 days after enrollment, and death. RESULTS Of the patients receiving unfractionated heparin, 40.2 percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175 of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312) of the patients receiving reviparin once daily. With regard to thrombus regression, reviparin administered twice daily was significantly more effective than unfractionated heparin (relative likelihood of thrombus regression, 1.28; 97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to 1.53). Mortality and the frequency of episodes of major bleeding were similar in the three groups. CONCLUSIONS In acute deep-vein thrombosis, reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus. Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe.
Stability and Guaranteed Cost Analysis of Time-Triggered Boolean Networks

This paper investigates stability and guaranteed cost of time-triggered Boolean networks (BNs) based on the semitensor product of matrices. The time triggering is generated by mode-dependent average dwell-time switching signals in the BNs. With the help of the copositive Lyapunov function, a sufficient condition is derived to ensure that the considered network is globally stable under a designed average dwell-time switching signal. Subsequently, an infinite time cost function is further discussed and its bound is presented according to the obtained stability result. Numerical examples are finally given to show the feasibility of the theoretical results.
Properties of the PriA Helicase Domain and Its Role in Binding PriA to Specific DNA Structures*

Primosome assembly protein PriA functions in the assembly of the replisome at forked DNA structures. Whereas its N-terminal DNA binding domain (DBD) binds independently to DNA, the affinity of DBD protein for forked structures is relatively weak. Although the PriA helicase domain (HD) is required for high affinity fork binding, HD protein had very low affinity for DNA. It had only low levels of ATPase activity, and it hydrolyzed ATP when DNA was absent whereas PriA did not. HD catalyzed unwinding of a minimal substrate composed of a duplex with a 3′ single-stranded tail. Single-strand binding protein (SSB) bound to the tail of this substrate inhibited this reaction by full-length PriA but enhanced the reaction by HD. SSB stabilized binding of PriA but not of DBD or HD to duplexes with a 5′ or 3′ single-stranded tail. On forked substrates SSB enhanced helicase action on the lagging-strand arm by PriA but not by HD. The results indicate that synergy of the DBD and HD allows stable binding at the interface between duplex and single-stranded DNA bound by SSB. This mode of binding may be analogous to fork binding, which orients the helicase to act on the lagging-strand side of the fork.