Miracle-dz/UniFAR-FTUs huggingface dataset:
Variability of mycophenolic acid elimination in the renal transplant recipients – population pharmacokinetic approach

Abstract The aim of this study was to develop a population pharmacokinetic (PK) model for clearance of mycophenolic acid (MPA) in adult renal transplant recipients, to quantify the PK parameters and the influence of covariates on the MPA pharmacokinetic parameters. Parameters associated with plasma concentrations of MPA at steady-state were analyzed in 70 renal transplant recipients (mean age 42.97 years; mean total body weight 75.33 kg) using nonlinear mixed-effect modeling (NONMEM). Characteristics of patients screened for influence on the pharmacokinetic parameters were gender, age, body weight, time after transplantation, whether the patient was diagnosed as having diabetes mellitus, organ source (living or deceased donor), biochemical parameters and co-therapy (tacrolimus, cyclosporine, prednisolone, omeprazole, bisoprolol, carvedilol, nifedipine). A validation set of 25 renal transplant recipients was used to estimate the predictive performance of population pharmacokinetic model. Typical mean value of MPA oral clearance, estimated by base model (without covariates) was 0.741 L h−1. During population modeling, the full model showed that clearance of the MPA was significantly influenced by age, total daily dose of MPA, creatinine clearance, albumin level, status and gender of a donor, and the nifedipine and tacrolimus co-therapy. In the final model, clearance of MPA was reported to be significantly influenced by age, total daily dose of MPA and thenifedipine co-therapy. The derived model describes adequately MPA clearance in terms of characteristics of our patients, offering basis for individual pharmacotherapy approach.
Activation of the Kexin from Schizosaccharomyces pombeRequires Internal Cleavage of Its Initially Cleaved Prosequence

ABSTRACT Members of the kexin family of processing enzymes are responsible for the cleavage of many proproteins during their transport through the secretory pathway. The enzymes themselves are made as inactive precursors, and we investigated the activation process by studying the maturation of Krp1, a kexin from the fission yeastSchizosaccharomyces pombe. Using a cell-free translation-translocation system prepared from Xenopuseggs, we found that Krp1 is made as a preproprotein that loses the presequence during translocation into the endoplasmic reticulum. The prosequence is also rapidly cleaved in a reaction that is autocatalytic and probably intramolecular and is inhibited by disruption of the P domain. Prosequence cleavage normally occurs at Arg-Tyr-Lys-Arg102↓ (primary cleavage site) but can occur at Lys-Arg82 (internal cleavage site) and/or Trp-Arg99 when the basic residues are removed from the primary site. Cleavage of the prosequence is necessary but not sufficient for activation, and Krp1 is initially unable to process substrates presented in trans. Full activation is achieved after further incubation in the extract and is coincident with the addition of O-linked sugars. O glycosylation is not, however, essential for activity, and the crucial event appears to be cleavage of the initially cleaved prosequence at the internal site. Our results are consistent with a model in which the cleaved prosequence remains noncovalently associated with the catalytic domain and acts as an autoinhibitor of the enzyme. Inhibition is then relieved by a second (internal) cleavage of the inhibitory prosequence. Further support for this model is provided by our finding that overexpression of a Krp1 prosequence lacking a cleavable internal site dramatically reduced the growth rate of otherwise wild-type S. pombecells, an effect that was not seen after overexpression of the normal, internally cleavable, prosequence or prosequences that lack the Lys-Arg102 residues.
Essays on Experimental and Quasi-Experimental Policy Design and Evaluation

xii CHAPTER I: HETEROGENEOUS TREATMENT EFFECTS AND MECHANISMS IN INFORMATION-BASED ENVIRONMENTAL POLICIES: EVIDENCE FROM A LARGESCALE NATURAL FIELD EXPERIMENT 1 1. Introduction 1 2. Experiments with Information-based Environmental Programs 3 3. Methodology 4 3.1. Heterogeneity in Treatment Responses 5 3.2. Nonparametric Tests 7 3.3. Quantile Treatment Effects 9 3.4. Subgroup Analysis 10 4. Experimental Design and Data 11 5. Results 13 5.1. Nonparametric Tests 13 5.2. Quantile Regressions 15 5.3. Subgroup Analysis 16 5.4. Targeting Information Campaigns 17 5.5. Mechanisms of the Strong Social Norm Message (Treatment 3) 18 5.5.1. Recurring behavioral changes versus one-shot technological investments 19 5.5.2. Outdoor versus indoor water use changes 20 5.5.3. Social versus private preferences 21 6. Conclusions 23 7. References 26 CHAPTER II: COMPARING EXPERIMENTAL AND NON-EXPERIMENTAL EVALUATION DESIGNS USING A LARGE-SCALE RANDOMIZED EXPERIMENT . 53 1. Introduction 53
Business link: Use, satisfaction and comparison with business shop and business connect

Abstract This paper assesses the level of use and satisfaction with Business Link services in England and Business Shop and Business Connect services in Scotland and Wales. These services are the result of government initiatives to provide support services to small and medium‐sized firms. The paper uses the large scale 1997 survey of the Cambridge ESRC Centre for Business Research. Important findings are that whilst use levels of Business Link are relatively high, they are focused chiefly on information, training and grants, with a secondary focus on specialist advice. The chief additions to the system as a result of DTI development, of personal advisors and diagnostic assessment, both have low use and satisfaction levels. A second key finding is that there are few statistically significant differences of satisfaction levels by firm type. Of greatest policy concern are: (i) the tension between the actual use patterns of BL services, which concentrate on information, grants and specialist advice, and their.
Governance in Sports Clubs: Evidence for the Island of Madeira

Abstract This paper analyses the pay and performance of the managing director (MD) of sports clubs on the island of Madeira, focusing on the role played by the economic performance of the club, together with that played by the structure of the board and the individual characteristics of the manager. If the MD can influence the board structure, agency problems arise, which in turn allows the MD to extract rent and demand remuneration in excess of the equilibrium level. The policy implication is derived.
INR vs. thrombin generation assays for guiding VKA reversal: a retrospective comparison

Abstract Background: Prothrombin complex concentrate (PCC) is used to reverse vitamin K antagonist (VKA)-induced anticoagulation. Prothrombin time-derived international normalized ratio (INR) measurements are widely used in determining the required PCC dose, but this approach requires reappraisal. The aim of the present study was to determine the added value of the thrombin generation assay (TGA) compared with the INR in guidance of VKA reversal by PCC. Methods: In an open, observational study, INR and TGA measurements were carried out on plasma samples from phenprocoumon-treated patients receiving VKA reversal. Following both analytical methods, PCC dosing correlates were calculated and compared retrospectively. Alternatively, in vitro PCC spiking experiments were performed. Results: As expected, an exponential relationship between PCC dose and INR was found. For the TGA parameters peak thrombin and endogenous thrombin potential (ETP), however, this relationship was found to be linear throughout the full therapeutic range. Additional computational analysis showed a positive correlation (r2=0.7) between the initial INR and PCC dose required for a target INR of 2.1, which was completely lost at a lower target INR. In contrast, a positive correlation (r2=0.8) between initial ETP as well as peak height and PCC dose required to obtain parameter normalization was found. These correlates appeared useful for calculating PCC dose. Conclusions: Our results support the current debate questioning the rationale for the use of the INR in the management of anticoagulation by VKA. Compared with INR, TGA-based calculations may enable a more accurate PCC dosing regimen for patients requiring VKA reversal.
JAK 2 and MPL Mutation Analysis in Myeloproliferative Neoplasms

©2014 Blue Cross and Blue Shield of Louisiana An independent licensee of the Blue Cross and Blue Shield Association No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from Blue Cross and Blue Shield of Louisiana. Page 1 of 16 Applies to all products administered or underwritten by Blue Cross and Blue Shield of Louisiana and its subsidiary, HMO Louisiana, Inc.(collectively referred to as the “Company”), unless otherwise provided in the applicable contract. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically.
Better Management of Patients with Osteoarthritis: Development and Nationwide Implementation of an Evidence-Based Supported Osteoarthritis Self-Management Programme.

BACKGROUND Information and exercise are core treatments of osteoarthritis. Self-management and coping strategies with the disease are crucial to gain benefits. We developed a supported osteoarthritis self-management programme, delivered by trained physiotherapists, to facilitate patient and healthcare compliance. The programme combined peer- and healthcare professional-delivered information, and individually adapted exercise. METHODS Physiotherapists were trained to deliver and evaluate the programme. Patient-reported compliance and satisfaction with the programme was assessed at three- and 12-month follow-ups. RESULTS Data from 20,200 consecutive patients in 320 different care centres in Sweden showed that 97% attended the theory sessions and 83% volunteered for the optional individual exercise programme. The intervention was rated as good or very good by 94% of patients. After three months, 62% reported daily use of what they had learned during the course, and 91% reported weekly use. Corresponding numbers after 12 months were 37% and 72%. CONCLUSIONS The supported osteoarthritis self-management programme is feasible in clinical practice, and seems useful and acceptable to patients.
Toehold Acquisitions, Shareholder Wealth, and the Market for Corporate Control

Abstract This study examines the valuation consequences of control-related outcomes that follow toehold acquisitions. We find evidence that toehold acquisitions facilitate value enhancing control transfers. The types of control transfers not only include takeovers, but also internal mechanisms, such as proxy fights and management turnovers. We find that toehold targets experiencing such control transfers exhibit an abnormal increase in share value, while those not experiencing such control transfers exhibit an abnormal decrease in share value. The results suggest that the positive valuation effect associated with toehold acquisitions reflects the expected benefits of subsequent control transfers.
Tubulin homolog TubZ in a phage-encoded partition system

Partition systems are responsible for the process whereby large and essential plasmids are accurately positioned to daughter cells during bacterial division. They are typically made of three components: a centromere-like DNA zone, an adaptor protein, and an assembling protein that is either a Walker-box ATPase (type I) or an actin-like ATPase (type II). A recently described type III segregation system has a tubulin/FtsZ-like protein, called TubZ, for plasmid movement. Here, we present the 2.3 Å structure and dynamic assembly of a TubZ tubulin homolog from a bacteriophage and unravel the Clostridium botulinum phage c-st type III partition system. Using biochemical and biophysical approaches, we prove that a gene upstream from tubZ encodes the partner TubR and localize the centromeric region (tubS), both of which are essential for anchoring phage DNA to the motile TubZ filaments. Finally, we describe a conserved fourth component, TubY, which modulates the TubZ-R-S complex interaction.
A Study of Motivations and the Image of Shanghai as Perceived by Foreign Tourists at the Shanghai EXPO

This study examines aspects of perceived motivations and images of foreign attendants at the Shanghai EXPO. Even though significant differences were found on several factors according to socio-demographic variables, there are inconsistent patterns. However, significant differences were found on all image domains between before EXPO and after EXPO. This indicates that the effects of hosting the EXPO were influential in changing image as perceived by foreign tourists. Relationships between motivations and image perceptions were found. For example, those who attended the Shanghai EXPO with motivation to seek novelty and excitement strongly perceived after attending EXPO that Shanghai is a cultural and historic city as well as an important economic center.
A Microeconomic Approach to Diffusion Models For Stock Prices

This paper studies a class of diffusion models for stock prices derived by a microeconomic approach. We consider discrete-time processes resulting from a market equilibrium and then apply an invariance principle to obtain a continuous-time model. the resulting process is an Ornstein-Uhlenbeck process in a random environment, and we analyze its qualitative behavior. In particular, we provide simple criteria for the stability or instability of the corresponding stock price model, and we give explicit formulae for the invariant distributions in the recurrent case. Copyright 1993 Blackwell Publishers.
Essential Elements of Treatment: A Comparative Study Between European and American Therapeutic Communities for Addiction

The purpose of this study was to investigate whether European and American therapeutic communities (TCs) for addiction, both traditional and modified, share a common perspective on what is essential in treatment using the Survey of Essential Elements Questionnaire (SEEQ). The European sample (N = 19) was gathered in 2009. For the American sample (N = 19), we used previously published research data. Despite comparable perspectives, European traditional TCs (N = 11) scored significantly higher than their American predecessors (N = 11) on four SEEQ domains. Cluster differences were more pronounced in Europe than in America.
Optimal Control of an Assembly System with Multiple Stages and Multiple Demand Classes

We consider an assembly system with multiple stages, multiple items, and multiple customer classes. The system consists of m production facilities, each producing a different item. Items are produced in variable batch sizes, one batch at a time, with exponentially distributed batch production times. Demand from each class takes place continuously over time according to a compound Poisson process. At each decision epoch, we must determine whether or not to produce an item and, should demand from a particular class arise, whether or not to satisfy it from existing inventory, if any is available. We formulate the problem as a Markov decision process and use it to characterize the structure of the optimal policy. In contrast to systems with exogenous and deterministic production lead times, we show that the optimal production policy for each item is a state-dependent base-stock policy with the base-stock level nonincreasing in the inventory level of items that are downstream and nondecreasing in the inventory level of all other items. For inventory allocation, we show that the optimal policy is a multilevel state-dependent rationing policy with the rationing level for each demand class nonincreasing in the inventory level of all nonend items. We also show how the optimal control problem can be reformulated in terms of echelon inventory and how the essential features of the optimal policy can be reinterpreted in terms of echelon inventory. Subject classifications: production and inventory control; systems with multiple echelons; inventory rationing; Markov decision processes; make-to-stock queues.
Innovation and internationalisation of Malaysia’s education sector through e-learning: facilitators

Organisational investments in information and communication technologies have increased significantly in the past two decades, with the aim of increasing individual productivity and thus, contributing to organisational productivity. However, such productivity increases occur only when these systems are efficiently deployed and accepted by potential users. In this paper we examine adoption (of e-learning technology) and drivers, as well as implications for internationalisation of Malaysia's education sector. The results show that e-learning perceived benefit (outcome orientation) and usage ease (process orientation) are the key drivers of adoption, and significantly moderated by users' attitude and internal control (self-efficacy). Since e-learning can be effectively used to serve international markets without having the international students relocate to Malaysia, the findings of this study can help to develop interventions to facilitate wider acceptance of this mode of delivery in the global education market.
[Increased homocysteine levels in polycystic ovary syndrome].

BACKGROUND AND OBJECTIVE Women with polycystic ovary syndrome (PCOS) exhibit frequently risk factors that predispose to cardiovascular disease. Hyperhomocysteinemia is an independent risk factor for this disease. The aim of this study was to know whether young women with PCOS have increased homocysteine levels. We also analyzed their possible relation with folate and vitamin B12 levels. PATIENTS AND METHOD Thirty nine patients with PCOS were studied; (age: mean [standard deviation] 28.9 [5.8] years), and 39 healthy women similar in age. We evaluated in all of them: smoking, menstrual cycles, hirsutism, body mass index, metabolic syndrome and levels of homocysteine, lipids, glucose, creatinine, folate, vitamin B12, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and androstendione. RESULTS Menstrual cycles, hirsutism, androstendione, LH levels and LH/FSH were higher, as we expected, in patients with PCOS. Moreover, patients had increased homocysteine (9.1 [2.1] vs 6.4 [1.8] micromol/L; p < 0.001) and glucose levels (99 [13] vs 88 [10] mg/dl; p < 0.001), a higher frequency of abnormal fasting glycemia (> 110 mg/dl) (23% vs 2.5%; p =.01) and lower folate levels (7.6 [3.7] vs 10.2 [3.6] ng/ml; p = 0.02). A multiple linear regression showed a negative association between homocysteine and folate levels (r2 = 0.05; p =.02). CONCLUSIONS Homocysteinemia is increased in women with PCOS, and it is negatively associated with folate levels.
Receptor noise as a determinant of colour thresholds

Inferences about mechanisms at one particular stage of a visual pathway may be made from psychophysical thresholds only if the noise at the stage in question dominates that in the others. Spectral sensitivities, measured under bright conditions, for di–, tri–, and tetrachromatic eyes from a range of animals can be modelled by assuming that thresholds are set by colour opponency mechanisms whose performance is limited by photoreceptor noise, the achromatic signal being disregarded. Noise in the opponency channels themselves is therefore not statistically independent, and it is not possible to infer anything more about the channels from psychophysical thresholds. As well as giving insight into mechanisms of vision, the model predicts the performance of colour vision in animals where physiological and anatomical data on the eye are available, but there are no direct measurement of perceptual thresholds. The model, therefore, is widely applicable to comparative studies of eye design and visual ecology.
The Role of Public-Sector Family Planning Programs in Meeting the Demand for Contraception in Sub-Saharan Africa.

CONTEXT Commonly used indicators of contraceptive behavior in a population-modern contraceptive prevalence (mCPR), unmet need for contraception, demand for contraception and demand satisfied-are not well-suited for evaluating the progress made by government family planning programs in helping women and men achieve their reproductive goals. METHODS Trends in these measures in 26 Sub-Saharan African countries between 1990 and 2014 were examined. Trends in a proposed new indicator, the public-sector family planning program impact score (PFPI), and its relationship to mCPR and the family planning effort score were also assessed. Case studies were used to review public family planning program development and implementation in four countries (Nigeria, Ethiopia, Rwanda and Kenya). RESULTS The four commonly used indicators capture the extent to which women use family planning and to which demand is satisfied, but shed no direct light on the role of family planning programs. PFPI provides evidence that can be used to hold governments accountable for meeting the demand for family planning, and was closely related to policy developments in the four case-study countries. CONCLUSIONS PFPI provides a useful addition to the indicators currently used to assess progress in reproductive health and family planning programs.
The Value of Full-Duplex for Cellular Networks: A Hybrid Duplex-Based Study

Recent work has demonstrated the gain of full-duplex (FD) network over half-duplex (HD) network in bidirectional sum throughput under the assumption of symmetric uplink-downlink traffic demands and perfect self-interference suppression (SIS). In this paper, we study the performance gain of FD network over HD network under asymmetric bidirectional traffic demands and non-ideal SIS. To this end, we investigate the traditional static time division duplex (TDD) transmission mode and the advanced dynamic TDD transmission mode to obtain the performance of HD network, and investigate the pure FD transmission mode and a flexible HD-FD hybrid transmission mode, namely, XD mode, to obtain the performance of FD network. We use the number of users supported by a network as performance metric, which is defined as the minimum of the weighted numbers of users supported in uplink and downlink given random traffic demands of users. To maximize the number of users, we optimize the bidirectional transmit power for pure FD mode, bidirectional time slot configuration for dynamic TDD mode, and both for XD mode. Numerical results show an evident gain of pure FD mode and XD mode over static TDD mode for different levels of traffic asymmetry, but the gain over dynamic TDD mode is marginal, which cannot justify the application of FD technology in cellular systems without advanced interference control mechanisms.