Miracle-dz/UniFAR-FTUs huggingface dataset:
EVEREST II high risk study based UK cost-effectiveness analysis of MitraClip® in patients with severe mitral regurgitation ineligible for conventional repair/replacement surgery

Abstract Objectives: To evaluate the cost-effectiveness of MitraClip, an interventional procedure for patients with chronic severe mitral regurgitation. Methods: A decision analytic model with a lifetime horizon was developed to assess the cost-effectiveness of MitraClip vs conventional medical management in patients with severe mitral regurgitation, ineligible for surgery. The analysis was performed from a UK NHS perspective and the estimates for mortality, adverse events, and cross-sectional NYHA class were obtained from the EVEREST II High Risk Study (HRS). Utility decrements were obtained from a heath technology assessment on Cardiac Resynchronization Therapy, while unit costs were obtained from national databases. The concept model was clinically validated. Costs (2011 £UK) and benefits were discounted at an annual rate of 3.5%. Results: Compared to medical management, over 2- and 10-year periods MitraClip had incremental Quality Adjusted Life Year (QALY) gains of 0.48 and 2.04, respectively. The Incremental Cost-Effectiveness Ratios for MitraClip at 2 and 10 years are £52,947 and £14,800 per QALY gained. Overall, the model was most sensitive to the choice of time horizon, the discount rate applied to benefits, the starting age of cohort, the utility decrement associated with NYHA II, and cost of the MitraClip procedure. The model was insensitive to changes in all other parameters. MitraClip was also found to be cost-effective, regardless of the modelling approach, and insensitive to the key assumptions of the procedure cost. Study limitations: The primary limitation of the analysis is the reliance on aggregate data from a modestly sized non-randomized study with a short-term follow-up period. Aligned to this was the need to extrapolate survival well beyond the study period in order to generate meaningful results. The impact of both of these limitations was explored via extensive sensitivity analyses. Conclusion: Compared to medical management, MitraClip is a cost-effective interventional procedure at conventional threshold values.
Schizophrenia and Automatic Processing: An Exploratory Study

This study deals with the schizophrenic deficit as one of automatic processing. To test the idea, a special experimental task was designed on which 21 schizophrenics, 21 depressives, and 21 normal subjects had to complete a series of simple geometric figures. When the subjects had thoroughly learned this activity, another information source, a brief story, was introduced, and the subjects had to pay attention to the story while they did the task. Two dependent variables were considered, execution time and performance. There were no differences among the three groups in the first experimental condition; but in the second condition, when the distractor was introduced, schizophrenics needed more time to do the task and their performance was noticeably worse than those of both normals and depressives. This outcome is explained in terms of a failure in the internal mechanisms which regulate the automatic, parallel, and unconscious processing.
Folate in gastrointestinal health and disease.

OBJECTIVE Folate has heterogeneous functions and is involved in several activities in both animal and human body. It is an important constituent of our organism, and its bioavailability is mainly dependent from the correct function of our gastrointestinal tract. Our aim is to describe what happens to folate homeostasis in gastrointestinal health and disease, analyzing the alterations of folate metabolism in some specific conditions of intestinal and liver impairment. DISCUSSION Folate absorption and metabolization involve the small intestine and the liver; in conditions of gastrointestinal tract disease (i.e. celiac disease, liver disease) folate function may be compromised with important consequences on the whole organism. Moreover, folate deficiency may produce gastrointestinal alterations too. For this reason, the gastrointestinal tract could be the responsible but also the victim of folate deficiency. CONCLUSIONS The presence of folate deficiency should always be assessed in patients with a gastrointestinal disease. Further studies are needed to assess the role of folates in gastrointestinal tract diseases and in other gynecologic, neurologic, psychiatric, cardiovascular, ophthalmic and neoplastic diseases. Folates supplementation could be considered, in the future, as an effective complimentary therapy in several pathologic conditions.
Corporate Governance, Managerial Compensation, and Disruptive Innovations

Whether a CEO manages the innovation efforts of the firm in line with shareholder preferences has a substantial impact on market value and firm growth, which in turn influence aggregate productivity growth and welfare. Using data on U.S. public firms, we find that (i) firms with better corporate governance tend to adopt highly incentivized contracts rich in stock options; and (ii) such contracts are more likely to lead to disruptive innovations -- patented inventions that are in the upper tail of the distribution in terms of quality and originality. We develop and estimate a new dynamic general equilibrium model of firm-level innovation with agency frictions and endogenous determination of executive contracts. The model is used to study the joint dynamics of corporate governance, managerial compensation, and disruptive innovations. Better corporate governance can reduce the influence of the CEO in the determination of the compensation structure. This leads to more incentivized contracts and boosts innovation, with substantial benefits for the shareholders, as well as the broader economy through knowledge spillovers. Shutting down the agency frictions leads to an increase in long-run output growth, which translates into a significant welfare gain in consumption equivalent terms.
Altered Expression of Tyrosine Kinases of the Src and Syk Families in Human T-Cell Leukemia Virus Type 1-Infected T-Cell Lines

ABSTRACT During the late phase of adult T-cell leukemia/lymphoma, a severe lymphoproliferative disorder caused by human T-cell leukemia virus type 1 (HTLV-1), leukemic cells no longer produce interleukin-2. Several studies have reported the lack of the Src-like protein tyrosine kinase Lck and overexpression of Lyn and Fyn in these cells. In this report we demonstrate that, in addition to the downregulation of TCR, CD45, and Lck (which are key components of T-cell activation), HTLV-1-infected cell lines demonstrate a large increase of FynB, a Fyn isoform usually poorly expressed in T cells. Furthermore, similar to anergic T cells, Fyn is hyperactive in one of these HTLV-1-infected T-cell lines, probably as a consequence of Csk downregulation. A second family of two proteins, Zap-70 and Syk, relay the signal of T-cell activation. We demonstrate that in contrast to uninfected T cells, Zap-70 is absent in HTLV-1-infected T cells, whereas Syk is overexpressed. In searching for the mechanism responsible for FynB overexpression and Zap-70 downregulation, we have investigated the ability of the Tax and Rex proteins to modulate Zap-70 expression and the alternative splicing mechanism which gives rise to either FynB or FynT. By using Jurkat T cells stably transfected with the tax and rexgenes or inducibly expressing the tax gene, we found that the expression of Rex was necessary to increase fynBexpression, suggesting that Rex controls fyn gene splicing. Conversely, with the same Jurkat clones, we found that the expression of Tax but not Rex could downregulate Zap-70 expression. These results suggest that the effect of Tax and Rex must cooperate to deregulate the pathway of T-cell activation in HTLV-1-infected T cells.
Empowering Patients to Co-Create a Sustainable Healthcare Value

Extensive literature suggests that a solution to the current problems of healthcare sustainability is the active involvement of patients in health management through the empowerment of their abilities. Latest marketing frameworks suggest that patients are important resources for co-creating health value together with operators. This research aims to analyze the effects of patient empowerment on patients’ value co-creation behaviors. An empirical survey was conducted on 250 patients with chronic diseases in Italy. The results, analyzed using the structural equation modeling, showed that their empowerment enhanced value co-creation behaviors. Patients apply their health competencies and resources in their co-creation of health service with operators. It is, therefore, important to empower patients in their transformation from passive to active stakeholders, working with providers for the most optimal health outcomes. This research provides practitioners with suggestions for patient involvement which utilizes their knowledge, capabilities and responsibility to improving healthcare services.
Genetic characterization of South American infectious bursal disease virus reveals the existence of a distinct worldwide-spread genetic lineage

Infectious bursal disease virus (IBDV) is one of the most concerning health problems for world poultry production. IBDVs comprise four well-defined evolutionary lineages known as classic (c), classic attenuated (ca), variant (va) and very virulent (vv) strains. Here, we characterized IBDVs from South America by the genetic analysis of both segments of the viral genome. Viruses belonging to c, ca and vv strains were unambiguously classified by the presence of molecular markers and phylogenetic analysis of the hypervariable region of the vp2 gene. Notably, the majority of the characterized viruses (9 out of 15) could not be accurately assigned to any of the previously described strains and were then denoted as distinct (d) IBDVs. These dIBDVs constitute an independent evolutionary lineage that also comprises field IBDVs from America, Europe and Asia. The hypervariable VP2 sequence of dIBDVs has a unique and conserved molecular signature (272T, 289P, 290I and 296F) that is a diagnostic character for classification. A discriminant analysis of principal components (DAPC) also identified the dIBDVs as a cluster of genetically related viruses separated from the typical strains. DAPC and genetic distance estimation indicated that the dIBDVs are one of the most genetically divergent IBDV lineages. The vp1 gene of the dIBDVs has non-vvIBDV markers and unique nucleotide and amino acid features that support their divergence in both genomic segments. The present study suggests that the dIBDVs comprise a neglected, highly divergent lineage that has been circulating in world poultry production since the early time of IBDV emergence.
Exchange Rate vs Foreign Price Passthrough Gap: Evidence From the European Gasoline Market

We show that European retail gasoline prices respond slower to changes in the dollar exchange rate than to changes in the international spot price of wholesale gasoline, which is quoted in dollars. This differential passthrough is not specific to the Euro, and is observed both for Euro-member states and also for those using national currencies. We examine the possibility that this pattern is driven by differences in either the variability and or persistence of exchange rates changes relative to those of the dollar price of gasoline, but find minimal supporting evidence for either. Refinery supply contracts treat changes in the dollar price and the exchange rate symmetrically, and are thus also an unlikely explanation. Other possibilities, such pricing to the market or pricing based on the country of origin are precluded by the nature of the product. There is evidence, however, that exchange rate fluctuations are more strongly correlated with country-specific economic conditions, which reduces the ability of firms to pass-through price increases and lessens their incentive to pass-through price decreases. Moreover, consumers likely draw a more direct link between the crude oil and retail gasoline prices, affecting their price expectations and search intensity, and optimal passthrough.
The NK1 Receptor Is Essential for the Full Expression of Noxious Inhibitory Controls in the Mouse

Behavioral analysis of the NK1 receptor gene knock-out (NK1−/−) mouse indicated that substance P was closely involved in orchestrating the physiological and behavioral response of the animal to major environmental stressors. In particular, endogenous pain control mechanisms, such as stress-induced analgesia were substantially impaired in mutant mice, suggesting a reduction in descending inhibitory controls to the spinal cord from the brainstem. To directly test the integrity of descending controls in NK1−/− mice, we have analyzed c-Fos expression in laminae I-II of the lumbar and cervical cord and in the rostral ventromedial medulla in an experimental paradigm known to require recruitment of descending inhibitory controls. Anesthetized mice were stimulated with water at 50°C either on their forepaw, hindpaw, or on both the hindpaw plus forepaw concurrently. Wild-type mice, naı̈ve or treated with an NK1 antagonist (RP67580) or its inactive isomer (RP68651), were compared with NK1−/− mice. C-Fos expression at the lumbar laminae I-II level was significantly reduced, whereas it was significantly greater in the raphe magnus and pallidus nuclei in the double stimulation situation in wild-type compared with NK1−/− mice. Blocking the NK1 receptor pharmacologically reproduced, in an enantiomere-selective manner, the data from NK1−/− mice, with no evidence for recruitment of descending inhibition at the lumbar cord level after forepaw stimulation. The present study demonstrates that the NK1 receptor is essential for the full development of noxiously evoked descending inhibition.
Characteristics of new single phase voltage doubler rectifier circuit using the partial switching strategy

In this paper, the new partial switching single phase voltage doubler rectifier circuit which can improve efficiency drastically is proposed. The partial switching circuit is circuit to realize boost and harmonic reduction, high efficiency in a good balance. The proposed circuit is different from conventional circuit[1] in the point that component of the partial switching is connected to DC side. Because current flowed through the different diode in partial switching and commutation in conventional circuit, the efficiency dropped. Because current flows through the same diode with both situations in proposed circuit, the efficiency is improved. With disposition to the DC side of the component of the partial switching, the diode which prevented the short circuit of the capacitor was necessary. But, the drop of the efficiency was suppressed at the minimum by operating two MOS-FET as synchronous rectification. The operating characteristic was inspected in experiment, and it was evaluated boost, harmonic current and efficiency. While equal performance about boost and harmonic current is maintained, 2–3% of efficiency was improved in comparison with conventional circuit[1]. In this paper, circuit configuration and a principle of operation, experimental results are reported.
[Clinical predictors for the phenotypic heterogeneity of severe hemophilia A in China].

OBJECTIVE To observe the phenotypic heterogeneity of severe hemophilia A in China and investigate the clinical factors for defining the severity of the clinical presentations. METHODS The data including the age of first bleeding and first joint bleeding, bleeding frequency, the number of joint deformities and body mass index (BMI) were collected from 223 patients with severe hemophilia A (FVIII:C≤2%). RESULTS The median age at first bleeding was 1 year (range: 0-35 years). The percentages of patients with first bleeding age<1 year, ≥2 years and ≥6 years were 44.3% (94/212), 34.4% (73/212), and 10.8% (23/212), respectively. The median age at first joint bleeding was 2.25 years. The percentages of patients with first joint bleeding age ≤1 year, ≥2 years and ≥6 years were 25.5% (24/94), 57.4% (54/94), and 18.1% (17/94), respectively. The percentage of patients who did not have joint bleeding was 7.4% (7/94). The median annual bleeding frequency was 24 per year (range: 1-120), and the proportion of patients with annual bleeding episodes of less than 6 times was 12.9%. Only 24.7% of the patients were free of any joint deformities. Analysis showed that milder cases had older ages of first bleeding and first joint bleeding than the severe cases, and the milder cases had also significantly lower BMI. CONCLUSION The age of first bleeding and first joint bleeding and BMI may predict the clinical severity of hemophilia A in China in the early stage.
B-Raf Is Critical For MAPK Activation during Mitosis and Is Regulated in an M Phase-dependent Manner in Xenopus Egg Extracts*

Activation of the MAPK cascade during mitosis is critical for spindle assembly and normal mitotic progression. The underlying regulatory mechanisms that control activation of the MEK/MAPK cascade during mitosis are poorly understood. Here we purified and characterized the MEK kinase activity present in Xenopus M phase-arrested egg extracts. Our results show that B-Raf was the critical MEK kinase required for M phase activation of the MAPK pathway. Consistent with this, B-Raf was activated and underwent hyperphosphorylation in an M phase-dependent manner. Interestingly B-Raf hyperphosphorylation at mitosis occurred, at least in part, as a consequence of a feedback loop involving MAPK-mediated phosphorylation within a conserved C-terminal SPKTP motif. The kinase activity of a B-Raf mutant defective at both phosphorylation sites was substantially greater than its wild type counterpart when incubated in Xenopus M phase egg extracts. Furthermore suppression of MAPK feedback at mitosis enhanced B-Raf activity, whereas constitutive activation of MAPK at mitosis strongly suppressed B-Raf activity. These results suggest that feedback phosphorylation by MAPK negatively regulates B-Raf activity at mitosis. Collectively our data demonstrate for the first time a role for B-Raf at mitosis and provide new insight into understanding the regulation and function of B-Raf during cell proliferation.
The use of oxalate to reduce dentin permeability under adhesive restorations.

PURPOSE To test a novel approach to reducing dentin permeability that localizes occlusion of dentin tubules by calcium oxalate crystals to the subsurface without lowering resin bond strengths to oxalate-treated dentin surfaces. MATERIALS AND METHODS Flat dentin surfaces of extracted human third molars were etched with a mass fraction of 32% phosphoric acid (Bisco) for 15 s and rinsed. Half of the surface was treated with a potassium oxalate gel (mass fraction of 3% monopotassium monohydrogen oxalate) for 2 mins. The entire surface was then moist bonded with either One Step (OS) or Scotchbond Multi-Purpose (SB) adhesive systems. A resin-based composite (Z-100) buildup was made over the entire surface. After storage for 24 hrs in distilled water, the teeth were longitudinally sectioned to separate the oxalate-treated half from the untreated (control) half. Each half was serially sectioned into several 0.7 mm thick slabs which were then trimmed to an hour-glass shape to reduce the bonded area to approximately 0.8 mm2 and tested in tension. Pre- and post-treatment hydraulic conductance (Lp) of dentin was determined using dentin discs with a standard protocol. SEM images were obtained to examine the effects of treatment both on the dentin surface and along the tubules beneath the surface. The bonded interface was also examined by SEM. RESULTS Treating etched dentin discs with the oxalate gel caused significant reduction of the Lp of dentin (80% reduction, P < 0.05). There were no statistically significant differences between bond strengths of oxalate-treated and untreated surfaces for either adhesive system. OS resulted in a bond strength of 25.8 +/- 9.2 MPa to untreated and 27.8 +/- 8.9 MPa to oxalate treated surfaces (P > 0.05). SB showed bond strengths of 22.9 +/- 7.9 MPa and 22.9 +/- 9.6 MPa to untreated and treated surfaces, respectively (P > 0.05). SEM images showed that the application of potassium oxalate gel on etched dentin resulted in the formation of crystals inside the tubules rather than on the surface. Examination of the bonded interfaces demonstrated that the crystal formation inside the tubules did not compromise the formation of a typical hybrid layer on the top of dentin surfaces. Resin monomers penetrated into the tubules filling the spaces around the crystals forming resin tags with a jagged-like feature.
If I do not have enough water, then how could I bring additional water for toilet cleaning?! Addressing water scarcity to promote hygienic use of shared toilets in Dhaka, Bangladesh

Provision of toilets is necessary but not sufficient to impact health as poor maintenance may impair toilet function and discourage their consistent use. Water in urban slums is both scarce and a prerequisite for toilet maintenance behaviours. We describe the development of behaviour change communications and selection of low‐cost water storage hardware to facilitate adequate flushing among users of shared toilets.
Letters of recommendation for surgical residencies: what they say and what they mean.

Screening of applicants and selection of interns for surgical residency programs continue to rely heavily on letters of recommendation from surgical faculty. To define important aspects of letters useful for screening and selection, letters written on behalf of housestaff with known performance and those of new applicants were circulated to a sample of 120 academic surgeons. Eighty letters, written on behalf of 42 students, were divided into 10 groups of 8; each group was sent to 12 individuals. Half of the letters were "open" (full letter-head and signature), and half were "text only" (i.e., no identification). Candidate names were omitted. Each faculty reviewer was asked to rank the candidate represented by each letter, for their program, on a scale of 1 to 5, and indicate key negative or positive phrases on individual letters. Reviewers were also asked to indicate the importance they generally ascribe in evaluating such letters to the school of origin, academic rank of the letter writer, personalization (of letter to reader), formal vs informal reference to the candidate, and mention of interest in specialty training. A response rate of 60% was obtained. Faculty reviewers stated explicitly that school of origin, personalization of the letter, and the academic rank of the writer are important factors influencing their ranking of candidate letters. The scores they gave to "open" and "text only" letters, however, do not differ significantly (P > 0.05). Letters were scored similarly, indicating that school of origin or writer may not be as critical as implied or believed. (ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of 21‐gauge and 22‐gauge aspiration needle during endobronchial ultrasound‐guided transbronchial needle aspiration

Background and objective: Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has typically been performed using the 22gauge (G) dedicated TBNA needle. Recently a new 21G TBNA needle has been introduced. The efficacy of using a larger gauge biopsy needle during EBUS‐TBNA has not been reported. The purpose of this study was to compare the diagnostic yield and utility of 21G and 22G needles during EBUS‐TBNA.