Miracle-dz/UniFAR-FTUs huggingface dataset:
Semiparametric estimation of treatment effects given base‐line covariates on an outcome measured after a post‐randomization event occurs

Summary. We consider estimation, from a double‐blind randomized trial, of treatment effect within levels of base‐line covariates on an outcome that is measured after a post‐treatment event E has occurred in the subpopulation 𝒫E,E that would experience event E regardless of treatment. Specifically, we consider estimation of the parameters γ indexing models for the outcome mean conditional on treatment and base‐line covariates in the subpopulation 𝒫E,E. Such parameters are not identified from randomized trial data but become identified if additionally it is assumed that the subpopulation 𝒫E,E of subjects that would experience event E under the second treatment but not under the first is empty and a parametric model for the conditional probability that a subject experiences event E if assigned to the first treatment given that the subject would experience the event if assigned to the second treatment, his or her outcome under the second treatment and his or her pretreatment covariates. We develop a class of estimating equations whose solutions comprise, up to asymptotic equivalence, all consistent and asymptotically normal estimators of γ under these two assumptions. In addition, we derive a locally semiparametric efficient estimator of γ. We apply our methods to estimate the effect on mean viral load of vaccine versus placebo after infection with human immunodeficiency virus (the event E) in a placebo‐controlled randomized acquired immune deficiency syndrome vaccine trial.
Research on Scale and Efficiency in Infrastructure Industry Based on Efficient Competition

This paper,based on panel data of 50 toll road business units from 2008 to 2010,through mathematical analysis of related variables which have influence on the profit index,defines the reasonable calculation range of economies of scale in toll road industry firstly;secondly,level of the scale economy and entry barriers are evaluated according to the minimum effective scale;thirdly,it probes into the cause of low level of economy scale and high level of entry barriers in toll road industry,and then puts forward two policy proposals of promoting privatization reform and crossing administrative district boundary combination.
Voice picking: analysis of critical factors through a case study in Brazil and the United States

Purpose - – The purpose of this paper is to identify and analyse the difficulties encountered in the implementation of a voice picking system at a large multinational company of the tractor industrial segment, outlining a comparison related to the main critical factors concerning the system implementation at a Brazilian and a USA plant. Design/methodology/approach - – The methodology utilised was qualitative and exploratory conducted through case studies in the two plants of the multinational company. The main data were collected through interviews with key managers directly involved in the project of voice picking system implementation. Findings - – The results indicate that the picking processes in the two plants were similar, since both were designed for the production line and conducted using bar-code readers and paper lists. Nevertheless, the internal warehousing process in the USA was more mature and computerised, whereas the Brazilian process still had opportunity for improvement, such as, the visual storage process, where the operator was responsible for locating an empty position. Research limitations/implications - – Since this research is an exploratory case study, its results cannot be generalised. Practical implications - – The paper provides relevant practical information and experiences to managers interested in implementing voice picking systems, as well as interested in improving the accuracy and productivity of logistics processes within warehouses. Originality/value - – The voice picking systems are more widespread in the USA than in Brazil, and therefore, companies around the world can use this studied case to better understand about the voice picking systems implementation process in both emerging and mature marketplaces.
Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine

OBJECTIVE Recent studies have demonstrated the short term efficacy of leflunomide. This study evaluates the efficacy and safety of leflunomide and sulfasalazine in rheumatoid arthritis over a two year follow up period. METHODS 358 patients with rheumatoid arthritis in a double blind trial were randomly allocated to receive either leflunomide 20 mg/day, placebo, or sulfasalazine 2 g/day. Those completing six months of treatment (n=230) were given the option to continue in 12 (n=168) and 24 (n=146) month double blinded extensions; the placebo group switched to sulfasalazine. This report compares efficacy and safety of leflunomide with sulfasalazine in the 6, 12, and 24 month patient cohorts. RESULTS The efficacy seen at six months was maintained at 12 and 24 months. Twenty four month cohorts on leflunomide showed significant improvement compared with sulfasalazine in doctor (−1.46 v−1.11, p=0.03) and patient (−1.61 v−1.04, p<0.001) global assessments, ACR20% response (82%v 60%, p<0.01), and functional ability (Δmean HAQ −0.65 v −0.36, p=0.0149; ΔHAQ disability index −0.89 v −0.60, p=0.059). Improvement in other variables was comparable for the two drugs, including slowing of disease progression. Improved HAQ scores in 6, 12, and 24 month leflunomide cohorts were seen in both non-responders (24%, 29%, 35%, respectivelyv sulfasalazine 8%, 10%, 27%) and ACR20% responders (leflunomide 63%, 62%, 66% vsulfasalazine 50%, 64%, 44%). Leflunomide is well tolerated at doses of 20 mg. No unexpected adverse events or late toxicity were noted during the two year period. Diarrhoea, nausea, and alopecia were less frequent with continued treatment. CONCLUSION These long term data confirm that leflunomide is an efficacious and safe disease modifying antirheumatic drug.
MR Imaging of Ampullary Carcinomas

Objective The purpose of this study was to demonstrate the appearance of ampullary carcinomas on MR images. Methods Sixteen patients with ampullary carcinomas underwent MR imaging. Tumor detectability, signal intensity of the tumor, and enhancement pattern on dynamic study were analyzed. MR cholangiopancreatography (MRCP) findings were assessed and were compared with the endoscopic retrograde cholangiopancreatography (ERCP) findings. Results Signal intensities of the tumor on each image were various. Dynamic study detected all tumors except one, and all detected tumors showed delayed enhancement. MRCP delineated more than half of the tumors as a filling defect within the duodenal fluid and clearly demonstrated pancreaticobiliary ductal. Conclusions Dynamic study is mandatory in diagnosing ampullary carcinoma, because it can depict most of the tumors, and delayed enhancement of such tumors is characteristic in case of ampullary carcinoma. MRCP can provide reliable information about pancreaticobiliary duct and it can replace diagnostic ERCP.
Limits to maximal performance.

Body size fundamentally affects maximal locomotor performance in mammals. Comparisons of performances of different-sized animals yield different results if made using relative, rather than absolute scales. Absolute speed may be a reasonable way to evaluate the locomotor performance of an animal that must escape predators in real time. However, comparisons of metabolic power in animals of different size can only be made meaningfully on a mass-specific basis. Numerous factors associated with the mechanics, energetics, and storage of elastic energy during locomotion change with body size, which results in allometric relationships that make the energetic cost of locomotion (alpha Mb-0.3) more expensive for small mammals than for large mammals. Small mammals have lower enzymatic capacities for anaerobic glycolysis (alpha Mb0.15) and higher specific aerobic capacities (alpha Mb-0.13) than large mammals. However, the energetic cost of transport increases more than aerobic power as mammals get smaller. The higher ratio of cost to available power in small mammals may explain why they run more slowly than large mammals, as a rule. Maximum aerobic capacity is allometrically related to body size. Limits to VO2max can be imposed by mitochondrial oxidative capacity, as in goats, or by the O2 transport system, as in humans and horses. No single step in the O2 transport system can limit the flux of O2 by itself; however, in an average non-athletic species of mammal, any of the steps in the system might appear to be the weakest link. In highly aerobic athletic species, and possibly elite athletic individuals of other species (e.g. humans), the malleable elements of the O2 transport system may develop to the point that their O2 transport capacities approach that of the least malleable element in the system, the lung. VO2max is very high in such individuals, and appears to be limited by simultaneous failure of all components of the O2 transport system.
Regenerative medicine cell therapies: numbers of units manufactured and patients treated between 1988 and 2010.

307 ISSN 1746-0751 10.2217/RME.10. 37 © 2010 Future Medicine Ltd Regen. Med. (2010) 5(3), 307–313 “Today, with a minimum baseline of 675,000 therapeutic units manufactured and 323,000 patients treated, we are undoubtedly a credible new sector of advanced healthcare that is proud to stand up and be counted. ” Regenerative medicine cell therapies: numbers of units manufactured and patients treated between 1988 and 2010
A Comprehensive Review of Prehospital and In-Hospital Delay Times in Acute Stroke Care

The purpose of this study was to systematically review and summarize prehospital and in-hospital stroke evaluation and treatment delay times. We identified 123 unique peer-reviewed studies published from 1981 to 2007 of prehospital and in-hospital delay time for evaluation and treatment of patients with stroke, transient ischemic attack, or stroke-like symptoms. Based on studies of 65 different population groups, the weighted Poisson regression indicated a 6·0% annual decline (P<0·001) in hours/year for prehospital delay, defined from symptom onset to emergency department arrival. For in-hospital delay, the weighted Poisson regression models indicated no meaningful changes in delay time from emergency department arrival to emergency department evaluation (3·1%, P=0·49 based on 12 population groups). There was a 10·2% annual decline in hours/year from emergency department arrival to neurology evaluation or notification (P=0·23 based on 16 population groups) and a 10·7% annual decline in hours/year for delay time from emergency department arrival to initiation of computed tomography (P=0·11 based on 23 population groups). Only one study reported on times from arrival to computed tomography scan interpretation, two studies on arrival to drug administration, and no studies on arrival to transfer to an in-patient setting, precluding generalizations. Prehospital delay continues to contribute the largest proportion of delay time. The next decade provides opportunities to establish more effective community-based interventions worldwide. It will be crucial to have effective stroke surveillance systems in place to better understand and improve both prehospital and in-hospital delays for acute stroke care.
Mechanisms of Polar Lobe Formation in Fertilized Eggs of Molluscs a b

Polar lobe formation in the marine mudsnail, Ilyanassa obsoleta, involves formation of a microtubule-, microfilament-dependent furrow that constricts at two rates, then stops and relaxes. Some artificial seawater mixtures allow relatively normal development, facilitate insertion of microelectrode tips, and prevent artifactual bleb formation during such punctures. Membrane events may affect formation of polar lobe constrictions: (1) Brief treatment with digitonin prevents constrictions, but not cytokinesis per se, and the suppression of constrictions is permanent. Tomatine (but not tomatidine) and filipin act similarly, although filipin often also stops cytokinesis as well. (2) Responses to digitonin, tomatine, and filipin occur with little change in membrane potential. (3) Adhesion to substrata in response to brief treatment at low pH prevents both constrictions and cytokinesis. (4) Adhesion to substrata via polylysine allows both constrictions and cytokinesis, but embryos are smaller in volume and develop abnormally. Formation of lobe constrictions may be sensitive to perturbations of the plasma membrane.
The Management of Crisis

Many business leaders defines a time of crisis as a moment which completely hinders society activity which ultimately leads to bankruptcy they prefer the choice of resentment downturn and do not consider it a key moment for the renewal ideas, ways of thinking, of policies and strategies adopted that mobilize around new ambitions, new development projects, new sales models, new businesses, new markets and do a crisis a moment of creation and innovation and collective revitalization. The purpose of this article is to study the various steps of the management of crisis and best management practices in times of crisis to be applied properly by the manager. Therefore, we would have to ask the following question: How can we ride a situation of crisis and provide benchmarks based on best management practices?
Chloride secretion by renal collecting ducts

Purpose of reviewRenal collecting ducts maintain NaCl homeostasis by fine-tuning urinary excretion to balance dietary salt intake. This review focuses on recent studies on transcellular Cl− secretion by collecting ducts, its regulation and its role in cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Recent findingsLumens of nonperfused rat medullary collecting ducts collapse in control media but expand with fluid following treatment with cAMP, demonstrating the capacity for both salt absorption and secretion. Recently, inhibition of apical epithelial Na+ channels (ENaC) unmasked Cl− secretion in perfused mouse cortical collecting ducts (CCDs), involving Cl− uptake by basolateral NKCC1 and efflux through apical Cl− channels. AVP, the key hormone for osmoregulation, promotes cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl− secretion. In addition, prostaglandin E2 stimulates Cl− secretion through both CFTR and Ca2+-activated Cl− channels. SummaryRenal Cl− secretion has been commonly overlooked because of the overwhelming capacity for the nephron to reabsorb NaCl from the glomerular filtrate. In ADPKD, Cl− secretion plays a central role in the accumulation of cyst fluid and the remarkable size of the cystic kidneys. Investigation of renal Cl− secretion may provide a better understanding of NaCl homeostasis and identify new approaches to reduce cyst growth in PKD.
Role of nuclear factor-κB in female breast cancer: a study in Indian patients.

INTRODUCTION The nuclear factor κB (NF-κB) is a super family of transcription factors which plays important roles in development and progression of cancer. The present investigation concerns NF-κB /p65 activity in human breast cancers with overexpression of ER, PR, HER-2/neu, as well as the significance of p65 expression with regard to menopausal status, stage, grade, tumor size, nodal status, and NPI of invasive ductal carcinomas in Eastern India. MATERIALS AND METHODS In this hospital based study 57 breast cancer patients attending a Breast Clinic of a reputed institute of Eastern India were assessed for p65 protein expression in breast tumor tissue samples by Western blotting. ER, PR and HER-2/neu expression was determined by immunohistochemistry. RESULTS NF-κB/p65 was significantly associated with advanced stage, large tumor size (≥5 cm), high grade, negative ER, negative PR, and positive HER-2/neu. High NF-κB/p65 expression was more frequent in patients with a high NPI (NPI≥5.4, 84.6%) compared with low NPI (<5.4, 44.4%) and this association was statistically significant (p=0.002). CONCLUSION NF-κB/p65 overexpression was associated with advanced stage, large tumor size, high grade, and high NPI which are poor prognostic factors linked to enhanced aggressiveness of the disease. NF-κB/p65 expression implies aggressive biological behavior of breast cancer and this study validates significant association of NF-κB /p65 overexpression with negative estrogen and progesterone receptor status and overexpression of HER-2/neu oncoprotein. In our good clinical practice, patients with NF-κB positive tumors need to be treated aggressively.
Continued Sports Activity, Using a Pain-Monitoring Model, during Rehabilitation in Patients with Achilles Tendinopathy

Background Achilles tendinopathy is a common overuse injury, especially among athletes involved in activities that include running and jumping. Often an initial period of rest from the pain-provoking activity is recommended. Purpose To prospectively evaluate if continued running and jumping during treatment with an Achilles tendon-loading strengthening program has an effect on the outcome. Study Design Randomized clinical control trial; Level of evidence, 1. Methods Thirty-eight patients with Achilles tendinopathy were randomly allocated to 2 different treatment groups. The exercise training group (n = 19) was allowed, with the use of a pain-monitoring model, to continue Achilles tendon-loading activity, such as running and jumping, whereas the active rest group (n = 19) had to stop such activities during the first 6 weeks. All patients were rehabilitated according to an identical rehabilitation program. The primary outcome measures were the Swedish version of the Victorian Institute of Sports Assessment—Achilles questionnaire (VISA-A-S) and the pain level during tendon-loading activity. Results No significant differences in the rate of improvements were found between the groups. Both groups showed, however, significant (P < .01) improvements, compared with baseline, on the primary outcome measure at all the evaluations. The exercise training group had a mean (standard deviation) VISA-A-S score of 57 (15.8) at baseline and 85 (12.7) at the 12-month follow-up (P < .01). The active rest group had a mean (standard deviation) VISA-A-S score of 57 (15.7) at baseline and 91 (8.2) at the 12-month follow-up (P < .01). Conclusions No negative effects could be demonstrated from continuing Achilles tendon-loading activity, such as running and jumping, with the use of a pain-monitoring model, during treatment. Our treatment protocol for patients with Achilles tendinopathy, which gradually increases the load on the Achilles tendon and calf muscle, demonstrated significant improvements. A training regimen of continued, pain-monitored, tendon-loading physical activity might therefore represent a valuable option for patients with Achilles tendinopathy.
The Role Of Unions In The Twenty First Century A Report For The Fondazione Rodolfo Debenedetti

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Glycerol kinase of Trypanosoma brucei. Cloning, molecular characterization and mutagenesis.

Trypanosoma brucei contains two tandemly arranged genes for glycerol kinase. The downstream gene was analysed in detail. It contains an ORF for a polypeptide of 512 amino acids. The polypeptide has a calculated molecular mass of 56 363 Da and a pI of 8.6. Comparison of the T. brucei glycerol kinase amino-acid sequence with the glycerol kinase sequences available in databases revealed positional identities of 39.0-50.4%. The T. brucei glycerol kinase gene was overexpressed in Escherichia coli cells and the recombinant protein obtained was purified and characterized biochemically. Its kinetic properties with regard to both the forward and reverse reaction were measured. The values corresponded to those determined previously for the natural glycerol kinase purified from the parasite, and confirmed that the apparent Km values of the trypanosome enzyme for its substrates are relatively high compared with those of other glycerol kinases. Alignment of the amino-acid sequences of T. brucei glycerol kinase and other eukaryotic and prokaryotic glycerol kinases, as well as inspection of the available three-dimensional structure of E. coli glycerol kinase showed that most residues of the magnesium-, glycerol- and ADP-binding sites are well conserved in T. brucei glycerol kinase. However, a number of remarkable substitutions was identified, which could be responsible for the low affinity for the substrates. Most striking is amino-acid Ala137 in T. brucei glycerol kinase; in all other organisms a serine is present at the corresponding position. We mutated Ala137 of T. brucei glycerol kinase into a serine and this mutant glycerol kinase was over-expressed and purified. The affinity of the mutant enzyme for its substrates glycerol and glycerol 3-phosphate appeared to be 3. 1-fold to 3.6-fold higher than in the wild-type enzyme. Part of the glycerol kinase gene comprising this residue 137 was amplified in eight different kinetoplastid species and sequenced. Interestingly, an alanine occurs not only in T. brucei, but also in other trypanosomatids which can convert glucose into equimolar amounts of glycerol and pyruvate: T. gambiense, T. equiperdum and T. evansi. In trypanosomatids with no or only a limited capacity to produce glycerol, a hydroxy group-containing residue is found as in all other organisms: T. vivax and T. congolense possess a serine while Phytomonas sp. , Leishmania brasiliensis and L. mexicana have a threonine.
Combined robotic-aided gait training and physical therapy improve functional abilities and hip kinematics during gait in children and adolescents with acquired brain injury

Abstract Purpose: To evaluate the combined effect of robotic-aided gait training (RAGT) and physical therapy (PT) on functional abilities and gait pattern in children and adolescents exiting acquired brain injury (ABI), through functional clinical scales and 3D-Gait Analysis (GA). Methods: A group of 23 patients with ABI underwent 20 sessions of RAGT in addition to traditional manual PT. All the patients were evaluated before and after the training by using the Gross Motor Function Measures (GMFM) and the Functional Assessment Questionnaire. Ambulant children were also evaluated through the 6 Minutes Walk Test (6MinWT) and GA. Finally, results were compared with those obtained from a control group of ABI children who underwent PT only. Results: After the training, the GMFM showed significant improvement in both dimensions ‘D’ (standing) and ‘E’ (walking). In ambulant patients the 6MinWT showed significant improvement after training and GA highlighted a significant increase in cadence, velocity and stride length. Moreover, hip kinematics on the sagittal plane revealed a statistically significant increase in range of motion (ROM) during the whole gait cycle, increased hip extension during terminal stance and increased ROM during the swing phase. Conclusions: The data suggest that the combined programme RAGT + PT induces improvements in functional activities and gait pattern in children and adolescents with ABI and demonstrated it to be an elective tool for the maintenance of the patients’ full compliance throughout the rehabilitative programme.