Miracle-dz/UniFAR-FTUs huggingface dataset:
Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens

Summary. Background: Prophylactic factor (F)VIII has been shown to reduce bleeds and arthropathy in patients with severe hemophilia A. Objectives: Assuming that the trough FVIII level is an important determinant of the efficacy of prophylaxis, this paper addresses the effect of the inter‐patient variability in pharmacokinetics and different dosing regimens on trough levels. Methods: Simulations used FVIII half‐lives and in vivo recoveries (IVR), observed during clinical trials with Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin‐Free Method], and commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis. Results and conclusions: Half‐life and dose frequency had a larger effect on trough FVIII and time per week with FVIII < 1 IU dL−1 than IVR and infused dose per kg. The combined effect of these parameters resulted in substantial inter‐patient variability in the amount of FVIII required to sustain a desired trough level. Prophylactic regimens based on Monday, Wednesday, Friday dosing were less cost effective in maintaining a desired trough level throughout the week. Dose escalation on Friday to cover the weekend would require potentially harmful doses of FVIII in many patients, especially in young children where more than 50% would require a Friday dose of over 100 IU kg−1 and some would require more than 400 IU kg−1. Knowledge of individual patients’ half‐lives and alteration of frequency of infusions may allow the more cost‐effective use of FVIII and potentially expand access to prophylaxis to a greater number of patients, especially in regions where healthcare resources are scarce.
Local economic linkages to community‐based tourism in rural Costa Rica

This paper reports on the contribution of tourism to the wellbeing of rural residents through the development of economic linkages engaged by community-based tourism (CBT) in rural Costa Rica. In a qualitative case study of local economic linkages surrounding one such project in Chira Island, economic linkages were assessed at two levels: discourse and practice. The findings indicate that CBT does not involve the collective property of the community, but rather, the collective property of a group of community members organized in a formal association. As a result, a discourse on local economic linkages has been promoted by CBT support organizations in which hopes of wider benefits are placed on small linkages to services and products provided by local community members. However, a field survey suggested that the economic linkages generated by CBT in the community were sporadic and polyvalent and, furthermore, that the linkages with agriculture are negatively affected by scale and seasonality, resulting in leakages out of the community. These findings caution practitioners that CBT may only have small-scale positive impacts on the local economy.
LEADERSHIP: CHARACTERISTICS AND THEORIES

Leadership is a process whereby an individual influences a group of individuals to achieve a common goal. Leadership in education requires certain key attributes. A leader must set a direction; he must equip those he leads to go in the direction he sets; and he must design the organization he leads around instruction. This involves clear communication of his vision, wise investment of resources, focus upon the goal, development of relationships and reference to the evidences of success as they occur. Leadership strategically and effectively impact teaching, learning and class activity. The place and the persons involved have immense influence on his actions and his behavior as a leader. It is essential for the leaders to understand the context which they are leading. This article highlights the meaning of leadership, some of its characteristics and theories of leadership.
How Spiritual Values and Worship Attendance Relate to Psychiatric Disorders in the Canadian Population

Objective: Research into risk and protective factors for psychiatric disorders may help reduce the burden of these conditions. Spirituality and religion are 2 such factors, but research remains limited. Using a representative national sample of respondents, this study examines the relation between worship frequency and the importance of spiritual values and DSM-IV psychiatric and substance use disorders. Method: In 2002, the Canadian Community Health Survey obtained data from about 37 000 individuals aged 15 years or older. While controlling for demographic characteristics, we determined odds ratios for lifetime, 1-year, and past psychiatric disorders, with worship frequency and spiritual values as predictors. Results: Higher worship frequency was associated with lower odds of psychiatric disorders. In contrast, those who considered higher spiritual values important (in a search for meaning, in giving strength, and in understanding life's difficulties) had higher odds of most psychiatric disorders. Conclusion: This study confirms an association between higher worship frequency and lower odds of depression and it expands that finding to other psychiatric disorders. The association between spiritual values and mood, anxiety, and addictive disorders is complex and may reflect the use of spirituality to reframe life difficulties, including mental disorders.
The development of a new cardiac auscultation test: How do screening and diagnostic skills differ?

Background: Newly qualified doctors are expected to be able to conduct a cardiac auscultation unassisted, but studies show conflicting results regarding cardiac auscultation skills. Methods: A two-part test instrument was designed containing innovative recordings of heart sounds from patients with common cardiac murmurs as well as healthy controls. A total number of 109 participants were tested, representing four levels of clinical experience. The content validity of the test instrument was studied by a postal questionnaire to 114 clinical teachers at the University Hospital of Aarhus, Denmark. Results: A significant correlation was found between level of experience and the ability to diagnose the conditions from which the murmurs originated (r = 0.45, P < 0.0001). No correlation was found between level of experience and the ability to identify persons with cardiac murmurs from healthy controls. All groups showed a tendency to interpret healthy heart sounds as cardiac murmurs. Conclusions: Diagnostic ability was found to correlate positively with clinical experience, whereas the ability to distinguish cardiac murmurs from normal heart sounds seems independent of clinical experience.
A Positive Economic Analysis of Products Liability

THIS paper asks whether the principal doctrines of products liability law are consistent with the hypothesis that the common law is best understood as an endeavor (which need not be conscious) to promote economic efficiency, taking the existing distribution of income and wealth as given.1 In contrast to most of the literature on products liability law, we emphasize positive rather than normative analysis, and we even offer some empirical analysis-a rarity in this field. Heavily criticized as a willful interference with the free market in goods and services,2 modern products liability law seems at first glance a powerful contradiction to the efficiency model. We shall argue, however, that both the historical development of the law and its current doctrinal structure are in the main consistent with efficiency. We emphasize this qualification. We shall not try to explain every decision-there are thousands every year. We shall not consider the day-to-day administration of the law, or even every doctrinal twist and turn-in fact, we identify several doctrines that are anomalies from an economic standpoint. We shall not discuss all the major doctrines of this immense field, an undertaking too ambitious for a single paper.
Phototropins Promote Plant Growth in Response to Blue Light in Low Light Environmentsw⃞

Phototropins (phot1 and phot2) are plant-specific blue light receptors for phototropism, chloroplast movement, leaf expansion, and stomatal opening. All these responses are thought to optimize photosynthesis by helping to capture light energy efficiently, reduce photodamage, and acquire CO2. However, experimental evidence for the promotion of plant growth through phototropins is lacking. Here, we report dramatic phototropin-dependent effects on plant growth. When plants of Arabidopsis thaliana wild type, the phot1 and phot2 mutants, and the phot1 phot2 double mutant were grown under red light, no significant growth differences were observed. However, if a very low intensity of blue light (0.1 μmol m−2 s−1) was superimposed on red light, large increases in fresh weight up to threefold were found in those plants that carried functional PHOT1 genes. When the intensity of blue light was increased to 1 μmol m−2 s−1, the growth enhancement was also found in the phot1 single mutant, but not in the double mutant, indicating that phot2 mediated similar responses as phot1 with a lower sensitivity. The effects occurred under low photosynthetically active radiation in particular. The well-known physiological phototropin-mediated responses, including chloroplast movement, stomatal opening, and leaf expansion, in the different lines tested indicated an involvement of these responses in the blue light–induced growth enhancement. We conclude that phototropins promote plant growth by controlling and integrating a variety of responses that optimize photosynthetic performance under low photosynthetically active radiation in the natural environment.
L 2 -discrete hedging in a continuous-time model

In the setting of the Black-Scholes option pricing market model, the seller of a European option must trade continuously in time. This is, of course, unrealistic from the practical viewpoint. He must then follow a discrete trading strategy. However, it does not seem natural to hedge at deterministic times regardless of moves of the spot price. In this paper, it is supposed that the hedger trades at a fixed number N of rebalancing (stopping) times. The problem (PN) of selecting the optimal hedging times and ratios which allow one to minimize the variance of replication error is considered. For given N rebalancing, the discrete optimal hedging strategy is identified for this criterion. The problem (PN) is then transformed into a multidimensional optimal stopping problem with boundary constraints. The restrictive problem (PN BS) of selecting the optimal rebalancing for the same criterion is also considered when the ratios are given by Black-Scholes. Using the vector-valued optimal stopping theory, the existence is shown of an optimal sequence of rebalancing for each one of the problems (PN) and (PN BS). It also shown BS that they are asymptotically equivalent when the number of rebalances becomes large and an optimality criterion is stated for the problem (PN). The same study is made when more realistic restrictions are imposed on the hedging times. In the special case of two rebalances, the problem (P2 BS) is solved and the problems (P2 BS) and (P2) are transformed into two optimal stopping problems. This transformation is useful for numerical purposes.
Crisis, sustainability of electricity prices and state interventions in Argentina

This article examines the sustainability of wholesale power prices following the 2001 economic crisis in Argentina. We depart from the contractual disputes between the multinational power generating companies and the state of Argentina, arising from price and investment interventions after the economic crisis. Then, we move on to argue that these sector-specific measures were inevitable once some of the key macroeconomic policies such as the currency board system were discarded. Using an error correction method and estimating a counterfactual price series, we demonstrate that in the absence of changes in the price determination method and direct public investment, the level and the volatility of power prices would have been much higher with further knock on effects on the rest of the economy. Copyright 2012 The Author 2011. Published by Oxford University Press on behalf of Associazione ICC. All rights reserved. , Oxford University Press.
Photooxidative stress‐induced and abundant small RNAs in Rhodobacter sphaeroides

Exposure to oxygen and light generates photooxidative stress by the bacteriochlorophyll a mediated formation of singlet oxygen (1O2) in Rhodobacter sphaeroides. Our study reports the genome‐wide search for small RNAs (sRNAs) involved in the regulatory response to 1O2. By using 454 pyrosequencing and Northern blot analysis, we identified 20 sRNAs from R. sphaeroides aerobic cultures or following treatment with 1O2 or superoxide (O–2). One sRNA was specifically induced by 1O2 and its expression depends on the extracytoplasmic function sigma factor RpoE. Two sRNAs induced by 1O2 and O–2 were cotranscribed with upstream genes preceded by promoters with target sequences for the alternative sigma factors RpoHI and RpoHII. The most abundant sRNA was processed in the presence of 1O2 but not by O–2. From this and a second sRNA a conserved 3′‐segment accumulated from a larger precursor. Absence of the RNA chaperone Hfq changed the half‐lives, abundance and processing of 1O2‐affected sRNAs. Orthologues of three sRNA genes are present in different alpha‐proteobacteria, but the majority was unique to R. sphaeroides or Rhodobacterales species. Our discovery that abundant sRNAs are affected by 1O2 exposure extends the knowledge on the role of sRNAs and Hfq in the regulatory response to oxidative stress.
The Uptake and Degradation of Matrix-bound Lipoproteins by Macrophages Require an Intact Actin Cytoskeleton, Rho Family GTPases, and Myosin ATPase Activity*

A key cellular event in atherogenesis is the interaction of macrophages with lipoproteins in the subendothelium.In vivo, these lipoproteins are bound to matrix and often aggregated, yet most cell-culture experiments explore these events using soluble monomeric lipoproteins. We hypothesized that the internalization and degradation of matrix-retained and aggregated low density lipoprotein (LDL) by macrophages may involve the actin-myosin cytoskeleton in a manner that distinguishes this process from the endocytosis of soluble LDL. To explore these ideas, we plated macrophages on sphingomyelinase-aggregated LDL bound to smooth muscle cell-derived matrix in the presence of lipoprotein lipase. The macrophages internalized and degraded the LDL, which was mediated partially by the LDL receptor-related protein. Cytochalasin D and latrunculin A, which block actin polymerization, markedly inhibited the uptake and degradation of matrix-retained LDL but not soluble LDL. Inhibition of Rho family GTPases by Clostridium difficiletoxin B blocked the degradation of matrix-retained and aggregated LDL by >90% without any inhibition of soluble LDL degradation. However, specific inhibition of Rho had no effect, suggesting the importance of Rac1 and Cdc42. Degradation of matrix-retained, but not soluble, LDL was also blocked by inhibitors of tyrosine kinase, phosphatidylinositol 3-kinase, and myosin ATPase. These findings define fundamental cytoskeletal pathways that may be involved in macrophage foam cell formation in vivo but have been missed by the use of previous cell culture models.
Hedge Fund Regulation Via Basel III

This Article is a rejoinder to a comment by Professor Romano on an earlier paper I coauthored with Christian Kirchner. Professor Romano suggests regulatory arbitrage, rather than the targeted regulation of bank lending to hedge funds under Basel III, as a hedge against systemic failure. I contend that it was not harmonization through Basel II but rather the profitability of certain assets and business strategies that caused banks to hold similar assets and engage in similar strategies. In particular, I find that the increasing role of hedge funds in the credit derivatives market, in combination with the market’s recent failure, suggests that an increased emphasis on banks’ lending exposure to hedge funds could be justified. Using the methodological approach of New Institutional Economics, I evaluate recent regulatory changes, including the U.S. Dodd-Frank Act, the AIFM Directive, and other pertinent regulation. I provide an impact analysis of regulatory changes, de lege lata and de lege ferenda, with a special emphasis on, and historical analysis of, hedge fund registration rules and asymmetric regulation in Dodd-Frank and the AIFM Directive.
GENDER INEQUALITY, SPOUSAL CAREERS AND DIVORCE

We present a model in which couples first match in the marriage markets and, on the basis of their relative spousal endowment levels, decide whether to have children, specialize in market production or homework and determine their intra-household allocations. After couples’ marriage match qualities are revealed, better-matched couples stay married and poorly-matched couples separate. A spousal education or endowment gap encourages couples to have children and specialize. The presence of children lowers the likelihood of divorce but the impact of children on the propensity to divorce is smallest among middle-income couples. The reason is that the latter react the least to changes in their marital status in making household allocations. Regardless of their marital status, high-productivity mothers go back to work after they have children. However, low-productivity, divorced mothers also go back to work if they had been married to low-productivity men who cannot support their offspring in separation. As the gender education or endowment gap narrows, couples tend to specialize less and have fewer or no children. These choices in turn feedback into a lower marital surplus and a higher likelihood of divorce. Thus, our model indicates that the spousal endowment or education gap can by itself account for the patterns of spousal specialization, the decision to have children, the likelihood of divorce, and the transfers between the spouses in divorce.
PharmGKB summary: very important pharmacogene information for SLC22A1

Organic cationic transporter 1 (OCT1, encoded by gene SLC22A1) is one of the three similar polyspecific cationic transporters mediating the uptake of many organic cations from the blood into epithelial cells. SLC22A1 is located in a cluster on chromosome 6 and contains seven exons and six introns. It can produce several alternatively spliced mRNA isoforms [1]. Similar to other members of the SLC22 family, the OCT1 protein contains 12 predicted α-helical transmembrane domains and a long hydrophilic loop between transmembrane domains 1 and 2 [2,3]. OCT1 is one of the major hepatic-uptake transporters located on the sinusoidal membrane of hepatocytes. It has substrate selectivity for a variety of endogenous ligands (dopamine, serotonin, choline), as well as cationic drugs, such as metformin, cimetidine, imatinib, oxaliplatin, tramadol, and agmatine [2,4–8]. This PharmGKB summary discusses SLC22A1 and its pharmacogenomic importance. A fully interactive version of this short review, with links to individual paper annotations can be found at: http://www.pharmgkb. org/gene/PA329#tabview = tab3&subtab = 33.
Noncardiac Surgery in Patients With Aortic Stenosis: A Contemporary Study on Outcomes in a Matched Sample From the Danish Health Care System

Past research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30‐day major adverse cardiovascular event (MACE) and all‐cause mortality were investigated in a contemporary Danish cohort.
IRC Botnet Major Issues and Solutions

The sharing of information during communication has been the main driver behind the research into criminal activities such as identity theft, phishing, and spam. Behind most of these activities are little programs that infect the users' system without the user's knowledge, or Botnets. The severity of such infections depends on the system's level of security, user awareness and the system's degree of vulnerability. There is a lot of paper that represent problem and detection methods, but the area of study is vast, hence this paper is deduced based on reviewed papers about this topic and clarified some problems and existing common solutions in a simple classification. Finally, paper tries to find the best solution for each problem regarding to related researches and resources.
Factors Influencing Restaurant Selection in Dublin

Abstract The primary objective of this research was to investigate the selection process used by consumers when choosing a restaurant to dine. This study examined literature on consumer behavior, restaurant selection, and decision-making, underpinning the contention that service quality is linked to the consumer's selection of a restaurant. It supports the utility theories that consumers buy bundles of attributes that simultaneously combined represent a certain level of service quality at a certain price. The findings of the research displayed a preference by Dublin consumers for Italian and Chinese styled restaurants and identified quality of the food, type of food, cleanliness of the restaurant, location and the reputation of the restaurant as the key decision variables/ attributes used by consumers to select restaurants. The study also established that the importance of the attributes changed, depending on the consumer's age, prior experience, their mood and the occasion involved.
Oxidized LDL Upregulates Angiotensin II Type 1 Receptor Expression in Cultured Human Coronary Artery Endothelial Cells: The Potential Role of Transcription Factor NF-&kgr;B

BackgroundWe demonstrated earlier that angiotensin II (Ang II), by AT1 receptor activation, upregulates oxidized LDL (ox-LDL) endothelial receptor LOX-1 gene expression and uptake of ox-LDL in human coronary artery endothelial cells (HCAECs). In this study, we investigated the regulation of Ang II receptors (AT1R and AT2R) by ox-LDL and the role of the redox-sensitive transcription factor NF-&kgr;B in this process. Methods and ResultsHCAECs were incubated with ox-LDL for 24 hours. Ox-LDL (10 to 40 &mgr;g protein/mL) upregulated AT1R but not AT2R, mRNA, or protein. Ox-LDL degraded I&kgr;B&agr; in cytoplasm and activated transcription factor NF-&kgr;B (P65) in HCAEC nuclear extract. Treatment of cells with the antioxidant &agr;-tocopherol (10 to 50 &mgr;mol/L) attenuated ox-LDL–mediated degradation of I&kgr;B&agr; and activation of NF-&kgr;B (P65) and inhibited the upregulation of AT1R mRNA and protein. The role of NF-&kgr;B signal transduction was further examined by use of an NF-&kgr;B inhibitor, caffeic acid phenethyl ester (CAPE). Pretreatment of cells with CAPE inhibited ox-LDL–mediated degradation of I&kgr;B&agr; and NF-&kgr;B activation and inhibited ox-LDL–induced upregulation of AT1R expression. Incubation of cells with both ox-LDL and Ang II increased cell injury, measured as cell viability and LDH release, compared with either ox-LDL or Ang II alone. &agr;-Tocopherol as well as the specific AT1R blocker CV11974 (candesartan) attenuated the cell-injurious effects of ox-LDL. ConclusionsThese observations suggest an important role of ox-LDL–mediated AT1R upregulation in cell injury. In this process, NF-&kgr;B activation seems to play a critical role in signal transduction. These findings provide a basis for the use of antioxidants and AT1R blockers in designing therapy of atherosclerosis.