Miracle-dz/UniFAR-FTUs huggingface dataset:
Catheter ablation as first-line treatment for paroxysmal atrial fibrillation: rarely a good value.

This editorial refers to ‘The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation: results from aMANTRA-PAF substudy? ’ by M.A. Aronsson et al . , on page 48–55. Over the past 10–15 years, catheter ablation has become an established treatment for patients with atrial fibrillation (AF) who prefer rhythm control. Based on multiple randomized trials, ablation is now strongly recommended (Class I, level of evidence A)1,2 as a second-line treatment for paroxysmal AF. In the second-line setting, the evidence that ablation is more effective than antiarrhythmic drugs at maintaining sinus rhythm is overwhelming,3 and this superior efficacy is accompanied by meaningful gains in quality of life.4 Additionally, these trials have formed the foundation for several cost-effectiveness (CE) models, which have consistently reported that ablation provides reasonable if not exceptional value in health economic terms. Previously published studies have found that the CE of AF ablation is contingent on the therapy improving the quality of life (and possibly reducing the risk of stroke) and sensitive to assumptions about time horizon.5,6 In contrast to the second-line setting, available data suggest that catheter ablation is only marginally more effective than antiarrhythmic drugs as a first-line treatment for paroxysmal AF. Data on this topic derive primarily from two completed multi-centre trials: Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF)7 and Radiofrequency Ablation vs. Antiarrhythmic drugs for atrial …
Insulin Hypersensitivity and Resistance to Streptozotocin-Induced Diabetes in Mice Lacking PTEN in Adipose Tissue

ABSTRACT In adipose tissue, insulin controls glucose and lipid metabolism through the intracellular mediators phosphatidylinositol 3-kinase and serine-threonine kinase AKT. Phosphatase and a tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/AKT pathway, is hypothesized to inhibit the metabolic effects of insulin. Here we report the generation of mice lacking PTEN in adipose tissue. Loss of Pten results in improved systemic glucose tolerance and insulin sensitivity, associated with decreased fasting insulin levels, increased recruitment of the glucose transporter isoform 4 to the cell surface in adipose tissue, and decreased serum resistin levels. Mutant animals also exhibit increased insulin signaling and AMP kinase activity in the liver. Pten mutant mice are resistant to developing streptozotocin-induced diabetes. Adipose-specific Pten deletion, however, does not alter adiposity or plasma fatty acids. Our results demonstrate that in vivo PTEN is a potent negative regulator of insulin signaling and insulin sensitivity in adipose tissue. Furthermore, PTEN may be a promising target for nutritional and/or pharmacological interventions aimed at reversing insulin resistance.
A Multi-Professional Short-Term Group Intervention for Informal Caregivers of Patients Using a Home Palliative Care Service

Informal carers of home palliative care patients have high unmet needs. However, interventions for carers are few. This research-based short-term group intervention addresses the information and support needs of carers. Multiprofessional informal teaching is combined with peer support. The intervention was designed by integrating the findings from a qualitative study and the evidence on needs and interventions, in order to address the key issues of feasibility, acceptability, and accessibility. Qualitative data from attendees showed that identifying with other carers and validating feelings, asking questions of professionals, and providing each other with support and encouragement were valuable outcomes from the group.
Foreign Direct Investment in the UK: Flows, Attitudes, and Implications+

Foreign Investment, both direct and portfolio, is a much discussed subject throughout the world. There are substantial measurement problems, but the attention does not generally focus on these. Rather the attention is on its effects. In the context of developing countries, there is much discussion of whether the investment is destabilising, producing financial instability and maybe even financial crises. This is not a focus of concern in developing countries. But there is often concern there also. Fears are expressed over the dangers such investment creates for jobs, innovation, research and perhaps growth. The theme of this paper is that while such fears seem to be felt in many EU countries, they are generally absent in the UK. We document this and set out the scale of investment flows into UK, before turning to explanation of the UK attitude. Our conclusion is that the attitude is in good part a result of the UK system of corporate governance. This separates ownership and control to a much greater degree than is the case in the countries of Continental Europe, and, by separating them, makes many of the usual fears over foreign investment unnecessary, and indeed irrelevant. This, we suggest, has implications for the future pattern of investment flows in the EU.
A Survey of Effects of International Trade on Growth

For many centuries economist simply upgrades Riccardian models and argued that free trade based on comparative advantage and according to geographical distribution of factors of production and specialization leads to efficient use of resources and increases world production frontier a “win-win” situation. While according to liberal economist trade liberalization creates faster growth there are economists who proclaimed that countries become more dependent on foreign resources which control process domestic growth and development. Recent models incorporate economies of scale, imperfect competition, R&D and assume that trade liberalization determine the geographical location of industries therefore gain from trade (Helpman and Krugman, 1985). This paper will review and contrast literatures on Old Trade theories, Post Keynesian, Endogenous Growth Models and International Trade, The New Trade Theory, Economic Geography and Theories of National Competitive Advantage.
A large gene family for putative variant antigens shared by human and rodent malaria parasites

A major mechanism whereby malaria parasites evade the host immune response to give chronic infections in patients' blood for months, or even years, is antigenic variation. In order to generate variant antigens, parasites require large multigene families. Although several gene families involved in these phenomena have been identified in the human malaria Plasmodium falciparum, to date no variant antigen gene families have been identified in malaria species that will infect widely used rodent laboratory hosts. Here we present, for the first time, to our knowledge, a large multigene family conserved in both rodent and human malarias, which is a strong candidate as a major variant antigen gene family. In each of four species of Plasmodium, three rodent malarias and the human pathogen P. vivax, homologues of the gene family were found to have a conserved three–exon structure. In the rodent malaria P. chabaudi, transcription of members of the gene family was developmentally regulated with maximum expression in late trophozoite stages, which is the developmental stage known to express variant antigen proteins.
Prevalence of human papillomavirus infection among female sex workers in Bulgaria

The present study estimates the prevalence and risk factors of human papillomavirus (HPV) infection among female sex workers (FSWs) in Bulgaria. HPV DNA was detected by polymerase chain reaction (PCR) in 43.4% of FSWs. HPV16 was the most common type, found in 17.0% of samples, followed by HPV31 (9.4%). Age and smoking were associated with a significantly greater risk of being infected. The results of this study indicate that FSWs in Bulgaria are at increased risk for cervical cancer and represent an important source of HPV infection for the general population in the country. They should be considered as a priority group in cervical cancer control programmes.
Learning Concept Hierarchies from Text Corpora using Formal Concept Analysis

We present a novel approach to the automatic acquisition of taxonomies or concept hierarchies from a text corpus. The approach is based on Formal Concept Analysis (FCA), a method mainly used for the analysis of data, i.e. for investigating and processing explicitly given information. We follow Harris' distributional hypothesis and model the context of a certain term as a vector representing syntactic dependencies which are automatically acquired from the text corpus with a linguistic parser. On the basis of this context information, FCA produces a lattice that we convert into a special kind of partial order constituting a concept hierarchy. The approach is evaluated by comparing the resulting concept hierarchies with hand-crafted taxonomies for two domains: tourism and finance. We also directly compare our approach with hierarchical agglomerative clustering as well as with Bi-Section-KMeans as an instance of a divisive clustering algorithm. Furthermore, we investigate the impact of using different measures weighting the contribution of each attribute as well as of applying a particular smoothing technique to cope with data sparseness.
High seroprevalence of bluetongue virus antibodies in goats in southeast Iran.

OBJECTIVE To describe the seroprevalence rate of bluetongue virus (BTV) in goat flocks in southeast of Iran. METHODS The blood samples were collected randomly from herds of southeast of Iran. A total of 93 sera samples were collected between 2011 and 2012. Antibodies to BTV in sera were detected by using a commercial competitive ELISA 3 according to manufacturer's instructions. RESULTS The seroprevalence rates were 67.7% for goats. Within a herd, prevalence of BTV seropositive animals ranged from 33.3% to 100.0%. All goat flocks were positive to BTV antibodies. CONCLUSIONS This study describes a high seroprevalence rate of BTV in goat flocks in southeast of Iran for the first time.
MERCI 1: A Phase 1 Study of Mechanical Embolus Removal in Cerebral Ischemia

Background and Purpose— To report the result of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 1 study, a phase 1 trial to evaluate the safety and efficacy of mechanical embolectomy in the cerebral vasculature. Methods— MERCI 1 enrolled 30 patients in 7 US centers. Main inclusion criteria were: National Institutes of Health Stroke Scale score (NIHSS) ≥10; treatment performed within 8 hours from symptoms onset and contra-indication to intravenous thrombolysis; no large hypodensity on computed tomography; and occlusion of a major cerebral artery on the angiogram. Safety was defined by the absence of vascular injury or symptomatic intracranial hemorrhage. Efficacy was assessed by recanalization rate and clinical outcome at 1 month. Significant recovery was defined as 30-day modified Rankin of 0 to 2 in patients with baseline NIHSS 10 to 20 and 30-day modified Rankin of 0 to 3 in patients with baseline NIHSS >20. The procedures were performed with the Merci Retrieval System, a system specially designed for intracranial embolectomy. Results— Twenty-eight patients were treated. Median NIHSS was 22. Median time from onset to completion of treatment was 6 hours and 15 minutes. Successful recanalization with mechanical embolectomy only was achieved in 12 (43%) patients, and with additional intra-arterial tissue plasminogen activator in 18 (64%) patients. There was one procedure related technical complication, with no clinical consequence. Twelve asymptomatic and no symptomatic intracranial hemorrhages occurred. At 1 month, 9 of 8 revascularized patients and 0 of 10 nonrevascularized patients had achieved significant recovery. Conclusion— This phase 1 study shows that cerebral embolectomy with the Merci Retriever was safe and that successful recanalization could benefit a significant number of patients, even when performed in an extended 8-hour time window.
Abnormal resting-state functional connectivity within the default mode network subregions in male patients with obstructive sleep apnea

Background and objective Abnormal resting-state functional connectivity (rs-FC) between the central executive network and the default mode network (DMN) in patients with obstructive sleep apnea (OSA) has been reported. However, the effect of OSA on rs-FC within the DMN subregions remains uncertain. This study was designed to investigate whether the rs-FC within the DMN subregions was disrupted and determine its relationship with clinical symptoms in patients with OSA. Methods Forty male patients newly diagnosed with severe OSA and 40 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (fMRI) examinations and clinical and neuropsychologic assessments. Seed-based region of interest rs-FC method was used to analyze the connectivity between each pair of subregions within the DMN, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), hippocampus formation (HF), inferior parietal cortices (IPC), and medial temporal lobe (MTL). The abnormal rs-FC strength within the DMN subregions was correlated with clinical and neuropsychologic assessments using Pearson correlation analysis in patients with OSA. Results Compared with GSs, patients with OSA had significantly decreased rs-FC between the right HF and the PCC, MPFC, and left MTL. However, patients with OSA had significantly increased rs-FC between the MPFC and left and right IPC, and between the left IPC and right IPC. The rs-FC between the right HF and left MTL was positively correlated with rapid eye movement (r=0.335, P=0.035). The rs-FC between the PCC and right HF was negatively correlated with delayed memory (r=-0.338, P=0.033). Conclusion OSA selectively impairs the rs-FC between right HF and PCC, MPFC, and left MTL within the DMN subregions, and provides an imaging indicator for assessment of cognitive dysfunction in OSA patients.
Estimation of wafer warpage profile during thermal processing in microlithography

Wafer warpage is common in microelectronics processing. Warped wafers can affect device performance, reliability, and linewidth control in various processing steps. Early detection will minimize cost and processing time. We propose in this article an in situ approach for estimating wafer warpage profile during the thermal processing steps in the microlithography process. The average air gap between wafer and bake-plate at multiple locations of a multizone bake-plate can be estimated and a profile can be obtained by joining these points. Experimental results demonstrate the feasibility and repeatability of the approach. This is a major improvement over our previously developed approach, in which only the average warpage could be obtained. The proposed approach requires no extra processing steps and time, as compared to conventional off-line methods.
Ubiquitin-Proteasome Pathway as a New Target for the Prevention of Restenosis

Background—The ubiquitin-proteasome system is the major intracellular protein degradation pathway in eucaryotic cells. It regulates central mediators of proliferation, inflammation, and apoptosis that are fundamental pathomechanisms in the development of vascular restenosis. Methods and Results—Effects of proteasome inhibition on neointima formation were studied in a balloon injury model in the rat carotid artery. Local application of the proteasome inhibitor MG132 (1 mmol/L) resulted in significant inhibition of intimal hyperplasia, that is, by 74% (P =0.008). This effect was accompanied by decreased proliferation, reduced infiltration of macrophages, and prolonged apoptosis, as determined by immunohistochemical and TUNEL analyses. Functional effects of proteasome inhibition on proliferation, activation of nuclear factor kappa B, and apoptosis were further characterized in rat primary vascular smooth muscle cells. MG132 dose-dependently inhibited vascular smooth muscle cell proliferation with 50% inhibition at 10 &mgr;mol/L. TNF&agr;-induced degradation of I&kgr;B&agr; and &bgr; was blocked, and activation of nuclear factor kappa B was suppressed in a concentration-dependent manner in bandshift assays. Moreover, proteasome inhibition (1 to 50 &mgr;mol/L MG132) induced apoptotic cell death up to 80%, as confirmed by DNA/Histone-ELISA and TUNEL-FACS analysis. Specificity of proteasome inhibition was shown by accumulation of multiubiquitinylated proteins and accumulation of specific proteasomal substrates. Conclusions—These proof-of-principle experiments demonstrate that inhibition of the ubiquitin-proteasome system effectively reduces neointima formation in vivo, which corresponds to strong antiproliferative, anti-inflammatory, and proapoptotic effects in vitro and in vivo. Our data suggest the ubiquitin-proteasome system as a new target in the prevention of vascular restenosis.
Mechanism of Prolongation of the R‐R Interval with Electrical Stimulation of the Carotid Sinus Nerves in Man

To elucidate the mechanism by which stimulation of the carotid sinus nerves prolongs the R-R interval, the effects of activating an implanted carotid sinus nerve stimulator were studied in eight patients at varying levels of background autonomic activity and with varying types of efferent autonomic blockade. Beta-receptor blockade was induced with intravenous propranolol, 0.20 mg/kg, and parasympathetic blockade with intravenous atropine, 0.04 mg/kg. In the supine position, average prolongation of the R-R interval due to stimulation of the carotid sinus nerves was 269 ± 56 msec prior to autonomic blocking drugs, 442 ± 214 msec after propranolol (NS), and 44 ± 13 msec after propranolol and atropine (P < 0.025). Comparable changes were produced in the standing position. With moderate treadmill exercise, stimulation of the carotid sinus nerves prolonged the R-R interval by only 40 ± 30 msec prior to blocking drugs, 62 ± 19 msec after propranolol, and 40 ± 30 msec after propranolol and atropine. It is concluded that the prolongation of the R-R interval produced by stimulation of the carotid sinus nerves is secondary to augmented parasympathetic activity, and the attenuation of this response during erect exercise appears to be due to a centrally mediated reduction in the responsiveness of the parasympathetic nervous system to baroreceptor stimuli.
Pharmacokinetics of Ceftaroline in Normal Body Weight and Obese (Classes I, II, and III) Healthy Adult Subjects

ABSTRACT The pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m2 and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of ≥40 kg/m2 compared to those <30 kg/m2. A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is ≥90% when the MIC is ≤1 μg/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at ClinicalTrials.gov under registration no. NCT01648127.)
p53 negatively regulates expression of FoxM1

The Forkhead box M1 (FoxM1) oncogenic transcription factor is overexpressed in a majority of human tumors. p53 is a transcription factor and a major tumor suppressor that is mutated in 50% of human cancers. In this study, we compared the levels of FoxM1 in normal BJ human fibroblasts, BJ fibroblasts with p53 knockdown and corresponding BJ immortal/oncogenic cell lines with inactivated p53. We found that partial deletion or inactivation of p53 in these cells leads to upregulation of FoxM1 expression. Similarly p53 knockdown in several human cancer cell lines with wt-p53 led to upregulation of FoxM1 mRNA and protein expression, while induction of p53 by DNA-damage led to downregulation of FoxM1. These data suggest that p53 negatively regulates FoxM1 expression and therefore inactivation of p53 in tumors could partially explain the phenomenon of FoxM1 overexpression in human cancers.
Histamine Upregulates Th1 and Downregulates Th2 Responses due to Different Patterns of Surface Histamine 1 and 2 Receptor Expression

Histamine, which acts via G protein-coupled receptors, is an important mediator of immediate hypersensitivity and is also able to influence the nature of T cell responses. We demonstrated that TH1 and Th2 cells express distinct surface histamine receptor patterns and that Th1-type responses are enhanced by histamine, whereas Th2-type responses are negatively regulated, due to different intracellular signals generated by histamine stimulation. These findings account for negative feedback regulation in a wide variety of pathologies.
The Common Cytokine Receptor γ Chain Controls Survival of γ/δ T Cells

We have investigated the role of common γ chain (γc)-signaling pathways for the development of T cell receptor for antigen (TCR)-γ/δ T cells. TCR-γ/δ–bearing cells were absent from the adult thymus, spleen, and skin of γc-deficient (γc −) mice, whereas small numbers of thymocytes expressing low levels of TCR-γ/δ were detected during fetal life. Recent reports have suggested that signaling via interleukin (IL)-7 plays a major role in facilitating TCR-γ/δ development through induction of V-J (variable-joining) rearrangements at the TCR-γ locus. In contrast, we detected clearly TCR-γ rearrangements in fetal thymi from γc − mice (which fail to signal in response to IL-7) and reduced TCR-γ rearrangements in adult γc thymi. No gross defects in TCR-δ or TCR-β rearrangements were observed in γc − mice of any age. Introduction of productively rearranged TCR Vγ1 or TCR Vγ1/Vδ6 transgenes onto mice bearing the γc mutation did not restore TCR-γ/δ development to normal levels suggesting that γc-dependent pathways provide additional signals to developing γ/δ T cells other than for the recombination process. Bcl-2 levels in transgenic thymocytes from γc − mice were dramatically reduced compared to γc + transgenic littermates. We favor the concept that γc-dependent receptors are required for the maintenance of TCR-γ/δ cells and contribute to the completion of TCR-γ rearrangements primarily by promoting survival of cells committed to the TCR-γ/δ lineage.