Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of drug clearance in children from adults: a comparison of several allometric methods.

AIMS In recent years with the advent of paediatric exclusivity and requirements to conduct clinical studies in children, the current emphasis is to find a safe and efficacious dose of a drug in children. It has been suggested that one can predict the clearance of a drug in children according to the equation: CL in the child=adult CLx(weight of the child/70)0.75. Considering the controversy surrounding the exponent of 0.75 for the prediction of clearance and lack of any systematic evaluation of the aforementioned proposal, the objectives of the study were as follows: (i) to determine if indeed the exponent 0.75 is the most suitable exponent for the prediction of clearance in children from adult data; (ii) to explore and search for other exponents that are more accurate or as good as 0.75; and (iii) to propose a new approach (if any) based on the findings of the current evaluation. METHODS Six methods were used to predict clearance of drugs in children from adult data. Besides evaluating the exponent of 0.75, exponents of 0.80, 0.85 and 1.0 were also evaluated. An empirical approach based on kidney and liver weights was also examined. Based on the results of five methods, a sixth method was introduced. RESULTS The results of the study indicate that no single method is suitable for all drugs or for all age groups. The exponents 0.75, 0.80, and 0.85 provided the same degree of accuracy or error in the prediction of clearance in children. CONCLUSIONS Since no single method is suitable for all drugs or for all age groups. A combination of approaches is suggested which may help in improving the prediction of clearance in children from adult data.
Prenatal and Postnatal Milk Supplementation and Adult Insulin-like Growth Factor I: Long-term Follow-up of a Randomized Controlled Trial

Objective: Insulin-like growth factors (IGF) are increasingly recognized as important determinants of adult health, in particular risk of certain cancers. However, little is known about the determinants of adult IGFs and to what degree they may be programmed by early life influences. Design: Randomized controlled trial of prenatal and postnatal milk supplementation among 951 subjects born in 1972 to 1974 in South Wales. Main outcome measure: Measures of IGF-I, IGF binding protein 3, and the molar ratio. Results: Data on adult IGFs were available from 663 subjects at a mean age of 25 years. Subjects in the intervention arm had lower IGF-I (−8.5 ng/mL; 95% confidence interval, −15.1 to −1.8, P = 0.01) and ratio (−1.20; 95% confidence interval, −2.33 to −0.04, P = 0.04). These differences could not be explained by follow-up bias or confounding factors. Conclusions: These results provide experimental data on the role of early life programming either in the intrauterine or postnatal period that may have long-term influences on the IGF axis, with potential implications for disease risk.
In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expression2Kinases (E2K). In the CCSs a total of 1,547 probe sets were identified that were overexpressed (FDR < 0.1). Comparing to CCCLs 560 probe sets (481 unique genes) had a cancer cell-specific expression profile, and 315 of these genes (65%) were validated. GSEA identified 5 cancer hallmarks enriched in CCSs (P < 0.01 and FDR < 0.25) showing that deregulation of the cell cycle is a major component of cervical cancer biology. E2K identified a protein-protein interaction (PPI) network of 162 nodes (including 20 drugable kinases) and 1626 edges. This PPI-network consists of 5 signaling modules associated with MYC signaling (Module 1), cell cycle deregulation (Module 2), TGFβ-signaling (Module 3), MAPK signaling (Module 4) and chromatin modeling (Module 5). Potential targets for treatment which could be identified were CDK1, CDK2, ABL1, ATM, AKT1, MAPK1, MAPK3 among others. The present study identified important driver pathways in cervical carcinogenesis which should be assessed for their potential therapeutic drugability.
Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy: reply from author

BACKGROUND The antitumour necrosis factor (TNF) activity of etanercept has been utilized to generate an important and novel treatment for rheumatoid arthritis. TNF has also been implicated in the pathogenesis of psoriasis. OBJECTIVES To determine whether blockade of TNF activity by etanercept may provide an additional treatment option for patients with psoriasis. METHODS In an uncontrolled trial, etanercept was added to the treatment regimen in six patients with severe recalcitrant psoriasis (three also with psoriatic arthritis) partially resistant to other ongoing systemic agents. RESULTS In each case, the disease activity showed marked improvement on addition of etanercept therapy. No added toxicity was found with etanercept. CONCLUSIONS Etanercept appears to be a promising immunomodulatory agent that can be used in combination therapy for the treatment of psoriasis, and a prospective controlled trial may be warranted.
Emergence of Multidrug-resistant Salmonella Paratyphi B dT+, Canada

We document an increase in the number of multidrug-resistant Salmonella enterica serovar Paratyphi B dT+ identified in Canada. Most of these strains harbor Salmonella genomic island 1 (SGI1). Further studies are needed to determine factors contributing to the observed emergence of this multidrug-resistant strain.
Shoulder Scoring Scales for the Evaluation of Rotator Cuff Repair

Various assessment tools have been proposed for evaluation of shoulder function. Analyses of comparability, validity, and reliability among shoulder assessment tools are lacking. The purpose of our investigation was to compare the results of three commonly used shoulder assessment tools in the evaluation of a specific shoulder condition. Seventy-two full-thickness rotator cuff tears were treated with an open rotator cuff repair from 1986–1993. The average age of the patients at surgery was 58 years (range, 24–92 years). The median duration of followup at the time of evaluation for this study was 55 months (range, 24–102 months; standard deviation, 22 months). Correlation among the results of the UCLA, Constant-Murley, and the Simple Shoulder Test scales was fair (range, 0.66–0.76). More importantly, the three systems were evaluated for their ability to accurately predict improved motion, strength, and patient satisfaction. The Simple Shoulder Test and the Constant-Murley scales showed the highest positive predictive values. The Simple Shoulder Test is a patient-based self-assessment device that easily can be incorporated into a busy clinical practice, providing outcome data comparable with complex evaluation systems when evaluating the results of rotator cuff repair.
Economic Returns to Education for Farm Households

This paper explores the causal effect of education on off-farm wages of farm operators and their spouses in Northern Ireland. In addition, it seeks to ascertain if there are differences in returns to education between rural and urban based individuals. A Mincerian human capital earnings equation is estimated to identify the marginal return to additional time spent in education by individuals according to location. In an extension of the initial model, instrumental variables are used to control for the potential endogeneity of education in the econometric estimation of the earnings equation. The analysis shows significant returns to education which are somewhat higher for females than males. However, returns are significantly lower for rural-based females than their urban counterparts. The paper also examines the returns to specific qualifications. We find that returns to higher qualifications (degree level) in the case of farm operators and especially their spouses are somewhat lower than comparable estimates for the Northern Ireland labour force as whole. This may indicate that rewards for high-level qualifications are probably constrained by the “thinness” of the labour markets in some rural areas. Introduction Historically education has been viewed as central to the formation of human capital (Schultz, 1960). Previous research evidence shows that better educated individuals earn higher wages and experience less unemployment than their less educated counterparts; providing evidence of strong financial returns to investing in education (Card, 1999). Within the UK, since the early 1970s, there has been a significant increase in the number of people obtaining educational qualifications. In more recent times, government policies, including the White Paper issued in early 2003, have pushed for expansion of the further and higher education sectors in order to meet rising skill needs; this drive being reiterated in the UK government’s goal of fifty per cent participation in higher education among the 18-30 age cohort by 2010 (Department of Education and Skills, 2003).
Influence of a metallic particle at a metal/insulator/gas triple junction in air and SF6

In gas insulated switchgears (GIS), high voltage electrodes are supported by solid insulators. A "triple junction" (TJ) exists at the interface between metal, insulating solid, and gas. This area constitutes a preferential zone were partial discharges (PDs) can appear. A further degradation of insulation performance can occur if solid particles accumulate at that place. This paper presents experiments carried out to obtain a quantitative account of the influence of a metallic particle located close to a triple junction area, both in dry air and SF6. PDs are detected and measured by conventional electrical measurements, and observed optically with a high-sensitivity intensified camera. Measurements under AC voltage show the influence of the particle on PD inception and flash-over voltage, in comparison with the same geometry without particle. In SF6, the particle induces a large decrease of PD inception and breakdown voltages, which become nearly independent of the gas pressure.
Potent and Sustained Antiviral Response of Raltegravir-based Highly Active Antiretroviral Therapy in HIV Type 1-infected Children and Adolescents

Background: There are pediatric patients receiving many highly active antiretroviral therapy (HAART) regimens entailing drug resistance mutations that complicate HAART effective therapies. Methods: This was a multicenter retrospective study of 19 multidrug-resistant children and adolescents enrolled from July 2007 to October 2009. Patients were nonresponders because no reduction in HIV type 1 (HIV-1) RNA to undetectable levels was observed during their previous antiretroviral treatment history. The long-term effectiveness of raltegravir (RAL)-based salvage therapy was assessed through a longitudinal analysis of immunologic, virologic, and clinical status of the patients. Results: Median age was 16.0 (15.0–18.0) years. At baseline, median HIV-1 RNA was 10,000 (4.0 log10 copies/mL) (interquartile range [IQR]: 4300–83,000), and median CD4+T-cell count was 329 (18.2% cells/&mgr;L) (IQR: 175–452). The backbone regimen included at least 1 fully active drug in 17/19 (89%) patients. Median follow-up with HAART including RAL was 80.1 weeks (IQR: 49.4–96.4): 16/19 (84%) exposed for >120 weeks and 6/19 (32%) >100 weeks. After RAL-based therapy, 4/19 (21%) patients achieved HIV-1 RNA <400 copies and 13/17 (68%) reached HIV-1 RNA <50 copies: 6 (32%) within the first month and 7 (37%) within the first 4 months. CD4+T-cell recovery (70% to 90% of the baseline values) was observed in 17/19 (89%) patients. No deaths, AIDS-defining illnesses, or symptoms of severe intolerance were recorded. Only 2 patients experienced mild-moderate short-term skin rash. Two (11%) patients had sustained and optimum adherence to HAART. No patients showed resistance mutations to RAL after follow-up. Conclusions: We observed a sustained antiviral response and improved immunologic indices in multidrug-resistant pediatric patients, most of whom had received RAL as part of salvage regimens with at least 1 fully active drugs.
Estudio bibliométrico sobre las monografías de artes marciales publicadas en España (1906-2006)

El presente estudio analiza desde una perspectiva bibliometrica las monografias sobre artes marciales publicadas en Espana entre 1906 y 2006. Partiendo del repertorio bibliografico de Perez y Gutierrez (2008) se estudia el numero total de monografias publicadas, numero de monografias por materia, numero de monografias por decada, y numero de monografias por materia y decada. Los resultados muestran un numero de 2.036 monografias (1.285 primeras ediciones). con un claro predominio de las artes marciales japonesas y chinas. Ocho materias superan el centenar de entradas (karate, judo/ jujutsu, taijiquan, wu-shu/ kung fu. clasicos, qigong, filosofia, historia y educacion, y aikido), revelandose dos modelos de evolucion. El primer modelo, propio de las artes marciales japonesas consideradas en conjunto y de las artes marciales enfocadas fundamentalmente hacia los aspectos utilitarios y/o de rendimiento deportivo (judo/jujutsu, karate y wu-shu/kung fu), evoluciona positivamente hasta los anos ochenta, momento en el que se estabiliza y/o retrocede. El segundo modelo, propio de las artes marciales chinas consideradas en conjunto, y de aquellas artes marciales centradas principalmente en los aspectos higienicos y/o espirituales (taijiquan, qigong, aikido), comienza un notable despegue en los anos 90 hasta la actualidad. La explicacion de estos modelos y de la propia evolucion de la produccion bibliografica sobre artes marciales en Espana pone de relieve aspectos como el desarrollo de la sociedad espanola y de la practica deportiva, de la produccion bibliografica, del habito de lectura, o las influencias culturales de los paises orientales en Espana.
Evaluation of thyroid shields for reduction of radiation exposure to orthopaedic surgeons.

BACKGROUND A perceived increase in the incidence of thyroid carcinoma in orthopaedic surgeons prompted an assessment of the use and value of thyroid shields in the operating theatre. METHODS The radiation exposure to the thyroid area of 19 orthopaedic trainees was measured over a 3-month period, while they were operating. The results were correlated with thyroid function tests and the number of emergency operative cases performed. RESULTS Thirteen trainees received radiation exposure within the guidelines set for the general population. Two trainees received exposure above this but within the guidelines set for occupational exposure. A thyroid shield reduced radiation exposure of the neck in one trainee by a factor of 13. The availability and usage of thyroid shields was low: only seven out of 13 trainees used shields. CONCLUSIONS A thyroid shield should be worn by orthopaedic surgeons if radiation is used during the operative procedure.
El yunque de hueso para afilar la hoz metálica dentada

No es infrecuente que en el contexto de excavaciones arqueologicas se localicen unos huesos especificamente trabajados en forma paralepipeda que han sido interpretados como elementos de caracter magico o simbolico por desconocimiento de su verdadera funcion. En realidad, estas piezas de hueso se utilizaban como yunque para obtener el dentado en la hoz metalica empleada para cortar el cereal. En efecto, en otro tiempo era habitual que los herreros realizaran el dentado mediante un martilleado sobre el borde cortante de la hoz, que se apoyaba directamente sobre el hueso buscando el efecto elastico del mismo.
Systematic Review and Meta-Analysis of the Significance of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates

ABSTRACT The prevalence of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) is 1.3% in published studies. Clinical associations include high-inoculum infections and glycopeptide failure, with hVISA infections associated with a 2.37-times-greater failure rate (95% confidence interval [CI], 1.53 to 3.67) compared to vancomycin-sensitive Staphylococcus aureus (VSSA) infections. Despite this, 30-day mortality rates were similar to those for VSSA infections (odds ratio [OR], 1.18; 95% CI, 0.81 to 1.74). The optimal therapy for hVISA requires further study.
Role of Outer Surface Protein D in the Borrelia burgdorferi Life Cycle

ABSTRACT Borrelia burgdorferi preferentially induces selected genes in mice or ticks, and studies suggest that ospD is down-regulated in response to host-specific signals. We now directly show that ospD expression is generally elevated within Ixodes scapularis compared with mice. We then assessed the importance of OspD throughout the spirochete life cycle by generating OspD-deficient B. burgdorferi and examining the mutant in the murine model of tick-transmitted Lyme borreliosis. The lack of OspD did not influence B. burgdorferi infectivity in mice or the acquisition of spirochetes by I. scapularis. OspD adhered to tick gut extracts in vitro, and the OspD-deficient B. burgdorferi strain had a threefold decrease in colonization of the tick gut in vivo. This decrease, however, did not alter subsequent spirochete transmission during a second blood meal. These data suggest that B. burgdorferi can compensate for the lack of OspD in both ticks and mice and that OspD may have a nonessential, secondary, role in B. burgdorferi persistence within I. scapularis.
Intrawound Vancomycin Decreases the Risk of Surgical Site Infection After Posterior Spine Surgery: A Multicenter Analysis

Study Design. Secondary analysis of data from a prospective multicenter observational study. Objective. The aim of this study was to evaluate the occurrence of surgical site infection (SSI) in patients with and without intrawound vancomycin application controlling for confounding factors associated with higher SSI after elective spine surgery. Summary of Background Data. SSI is a morbid and expensive complication associated with spine surgery. The application of intrawound vancomycin is rapidly emerging as a solution to reduce SSI following spine surgery. The impact of intrawound vancomycin has not been systematically studied in a well-designed multicenter study. Methods. Patients undergoing elective spine surgery over a period of 4 years at seven spine surgery centers across the United States were included in the study. Patients were dichotomized on the basis of whether intrawound vancomycin was applied. Outcomes were occurrence of SSI within postoperative 30 days and SSI that required return to the operating room (OR). Multivariable random-effect log-binomial regression analyses were conducted to determine the relative risk of having an SSI and an SSI with return to OR. Results. A total of 2056 patients were included in the analysis. Intrawound vancomycin was utilized in 47% (n = 966) of patients. The prevalence of SSI was higher in patients with no vancomycin use (5.1%) than those with use of intrawound vancomycin (2.2%). The risk of SSI was higher in patients in whom intrawound vancomycin was not used (relative risk (RR) -2.5, P < 0.001), increased number of levels exposed (RR -1.1, P = 0.01), and those admitted postoperatively to intensive care unit (ICU) (RR -2.1, P = 0.005). Patients in whom intrawound vancomycin was not used (RR -5.9, P < 0.001), increased number of levels were exposed (RR-1.1, P = 0.001), and postoperative ICU admission (RR -3.3, P < 0.001) were significant risk factors for SSI requiring a return to the OR. Conclusion. The intrawound application of vancomycin after posterior approach spine surgery was associated with a reduced risk of SSI and return to OR associated with SSI. Level of Evidence: 2
Oxcarbazepine for Treatment of Partial Epilepsy: A Review and Recommendations for Clinical Use

Recent trials and extensive postmarketing use confirm the efficacy and safety of oxcarbazepine (OXC) as a first-line treatment for adults and children with simple partial seizures, complex partial seizures, and partial seizures evolving to secondarily generalized seizures. OXC undergoes reductive metabolism at its keto moiety to form 10-hydroxy-10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide (MHD), which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes. OXC has some drug interactions, and does not require titration, allowing for better tolerability. Titration for monotherapy and adjunctive therapy of OXC could begin at 150 mg/day and be increased by 150 mg every 2-3 days until the target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments up to 600 mg/day if necessary for seizure control. Conversion to monotherapy can be done overnight or gradually. For gradual conversion, use the recommended titration of OXC and withdraw the baseline antiepileptic drugs gradually by 25%, starting at Day 14 or earlier in case of baseline tolerability issues. Consider reducing the dose of the primary antiepileptic drug during adjunctive therapy in case of adverse events or increase the dose of OXC in case of incomplete seizure control. In children OXC should be started at 8-10 mg/kg/day in two or three divided doses. If clinically indicated the dose can then be increased by 10 mg/kg/day in weekly intervals with final doses up to 30-46 mg/kg/day. Dose adjustment may be necessary in very young children (age 2-5 years) and in patients with renal dysfunction, based on renal clearance. However no adjustment of OXC dose is needed in patients with mild to moderate hepatic dysfunction. OXC has a number of advantages which include rapid titration, no need for safety monitoring (except for uncommon and mostly asymptomatic hyponatremia), a low potential for drug-drug interactions (except for those possibly impairing the effectiveness of oral contraceptives and increasing the serum concentration of phenytoin), a rash rate of less than 5%, similar efficacy and similar or better tolerability and safety compared with first-generation antiepileptic drugs. OXC is a valuable alternative to current treatment options.
Effect of mn on structural and dielectric properties of Pb(Zr0.5Tti0.48)O3 electroceramic

Lead zirconate titanate (PZT) samples were prepared near morphotropical phase boundary (MPB) (i.e., Pb(Zr0.52-xMnxTi0.48)O3 (x = 0, 0.02, 0.06, 0.10)). These samples were prepared using solid-state reaction technique. Formation of compounds was confirmed by X-ray diffraction (XRD), as a part of our preliminary structural analysis. We observed a significant change in grain size and density on the sample surface due to substitution of Mn. This microstructural analysis of the sample surface was done by scanning electron microscopy (SEM). Tc shift, dielectric constant improvement and reduction in the disordering of the material were observed while doing the detailed studies of the dielectric properties.