Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Clinical Pharmacists’ Recommendations on a Proton Pump Inhibitor Taper Protocol in an Ambulatory Care Practice

BACKGROUND: Previous studies have demonstrated an association between chronic proton pump inhibitor (PPI) utilization and adverse events such as fractures, infections, hypomagnesemia, and vitamin B12 deficiency. Because patients taking PPIs for an extended period of time are more susceptible to these adverse events, an approach to tapering patients off PPIs is clinically warranted. OBJECTIVES: To evaluate the impact of clinical pharmacists’ recommendations to clinicians to decrease PPI use in patients when chronic therapy is not indicated. METHODS: Clinical pharmacists electronically sent PPI taper recommendations for qualifying patients to primary care providers the day before each patient’s appointment. Using insurance claims data, an average pills per month (PPM) count was calculated for the 5-month period prior to initiating the PPI taper as well as for the 5-month period after the date of taper initiation. The PPM count was calculated by dividing the total number of pills a patient received by the total number of days in that period, multiplied by 30. The primary outcome for the study was the change in average PPM count from baseline (pretaper period) to follow-up (posttaper period) and was assessed using a paired t-test. Secondary outcomes included change in total annualized PPI costs to the organization, proportion of patients who began the taper protocol after primary care provider recommendation, and whether baseline characteristics were predictors of successful response. Change in annualized PPI costs to the organization was calculated by multiplying the average unit cost per pill (determined using a weighted average of the average wholesale price of the individual drugs) by the PPM change seen with the primary outcome and by the number of patients included in the study and expressed over the period of a full year. Logistic regression analysis was used to determine whether baseline variables including alcohol and tobacco use, diagnosis related to PPI use, PPI dose, dosing frequency, gender, and length of prior PPI use significantly impacted successful tapering. RESULTS: Average PPM count decreased by 8.7 pills (95% CI: 6.4, 11.1), from 25.6 at baseline (95% CI: 23.1, 28.1) to 16.9 at follow-up (95% CI: 14.3, 19.5; P less than 0.001). For the 117 evaluable patients in the study, there was an annualized PPI cost reduction of $18,151. 37.6% (44/117) of pharmacist-recommended tapers were enacted upon by primary care providers at the patient visit. Baseline patient characteristics were not found to be predictors of a successful taper response. CONCLUSIONS: Clinical pharmacist intervention may decrease overutilization of PPIs and associated costs in the primary care setting. While a decrease in PPI use was observed in this study, these findings do not imply improvement in clinically meaningful patient outcomes.
Hydrolysis of penicillins and related compounds by the cell-bound penicillin acylase of Escherichia coli.

1. A method is given for the preparation of penicillin acylase by using Escherichia coli N.C. I.B. 8743 and a strain selected for higher yield. The enzyme is associated with the bacterial cells and removes the side chains of penicillins to give 6-amino-penicillanic acid and a carboxylic acid. 2. The rates of penicillin deacylation indicated that p-hydroxybenzylpenicillin was the best substrate, followed in diminishing order by benzyl-, dl-alpha-hydroxybenzyl-, 2-furylmethyl-, 2-thienylmethyl-, d-alpha-aminobenzyl-, n-propoxymethyl- and isobutoxymethyl-penicillin. Phenylpenicillin and dl-alpha-carboxybenzylpenicillin were not substrates and phenoxymethyl-penicillin was very poor. 3. Amides and esters of the above penicillins were also substrates for the deacylation reaction, as were cephalosporins with a thienylmethyl side chain. 4. For the deacylation of 2-furylmethylpenicillin at 21 degrees the optimum pH was 8.2. The optimum temperature was 60 degrees at pH7. 5. By using selection A of N.C. I.B. 8743 and determining reaction velocities by assaying yields of 6-amino-penicillanic acid in a 10min. reaction at 50 degrees and pH8.2, the K(m) for benzylpenicillin was found to be about 30mm and the K(m) for 2-furylmethylpenicillin, about 10mm. The V(max.) values were 0.6 and 0.24mumole/min./mg. of bacterial cells respectively.
Glucosylceramidase Mass and Subcellular Localization Are Modulated by Cholesterol in Niemann-Pick Disease Type C*

Niemann-Pick disease type C (NPC) is characterized by the accumulation of cholesterol and sphingolipids in the late endosomal/lysosomal compartment. The mechanism by which the concentration of sphingolipids such as glucosylceramide is increased in this disease is poorly understood. We have found that, in NPC fibroblasts, the cholesterol storage affects the stability of glucosylceramidase (GCase), decreasing its mass and activity; a reduction of cholesterol raises the level of GCase to nearly normal values. GCase is activated and stabilized by saposin C (Sap C) and anionic phospholipids. Here we show by immunofluorescence microscopy that in normal fibroblasts, GCase, Sap C, and lysobisphosphatidic acid (LBPA), the most abundant anionic phospholipid in the endolysosomal system, reside in the same intracellular vesicular structures. In contrast, the colocalization of GCase, Sap C, and LBPA is markedly impaired in NPC fibroblasts but can be re-established by cholesterol depletion. These data show for the first time that the level of cholesterol modulates the interaction of GCase with its protein and lipid activators, namely Sap C and LBPA, regulating the GCase activity and stability.
Identification of Direct and Indirect Social Network Effects in the Pathophysiology of Insulin Resistance in Obese Human Subjects

Objective The aim of the present study was to examine to what extent different social network mechanisms are involved in the pathogenesis of obesity and insulin-resistance. Design We used nonparametric and parametric regression models to analyse whether individual BMI and HOMA-IR are determined by social network characteristics. Subjects and Methods A total of 677 probands (EGO) and 3033 social network partners (ALTER) were included in the study. Data gathered from the probands include anthropometric measures, HOMA-IR index, health attitudes, behavioural and socio-economic variables and social network data. Results We found significant treatment effects for ALTERs frequent dieting (p<0.001) and ALTERs health oriented nutritional attitudes (p<0.001) on EGO's BMI, establishing a significant indirect network effect also on EGO's insulin resistance. Most importantly, we also found significant direct social network effects on EGO's insulin resistance, evidenced by an effect of ALTERs frequent dieting (p = 0.033) and ALTERs sport activities (p = 0.041) to decrease EGO's HOMA-IR index independently of EGO's BMI. Conclusions Social network phenomena appear not only to be relevant for the spread of obesity, but also for the spread of insulin resistance as the basis for type 2 diabetes. Attitudes and behaviour of peer groups influence EGO's health status not only via social mechanisms, but also via socio-biological mechanisms, i.e. higher brain areas might be influenced not only by biological signals from the own organism, but also by behaviour and knowledge from different human individuals. Our approach allows the identification of peer group influence controlling for potential homophily even when using cross-sectional observational data.
Incorporating PV Inverter Control Schemes for Planning Active Distribution Networks

The distribution network planning under active network management (ANM) schemes is becoming of interest due to substantial benefits in facilitating the increasing integration of renewable energy sources. This paper presents various potential ANM schemes based on the photovoltaic inverter control (PVIC) considering enhanced utilization of the inverter reactive power capability. Depending on the active power generation of PV arrays, inverter size and desired reactive power settings, several PVIC schemes are proposed. The PVIC schemes are incorporated in the optimal power flow (OPF) and formulated as a nonlinear programming (NLP) problem. In this study, the PVIC schemes are applied to maximize the total wind-distributed generation (DG) penetration on a typical U.K. distribution system. Various case studies are presented and compared to evaluate the performance. The results show that the proposed schemes can significantly increase the wind penetration levels by 45.4% and up to 92.3%.
Centre De Referència En Economia Analítica Barcelona Economics Working Paper Series Competition and Well-being Competition and Well-being

We study the effects of competition in a context in which people's actions can not be contractually fixed. We find that in such an environment the very presence of competition does neither increase efficiency nor does it yield any payoff gains for the short side of the market. We also find that competition has a strong negative impact on social well-being, the disposition towards others, and individually experienced well-being, the emotional state, of those on the long side of the market. We conjecture that this limits the possibilities of satisfactory interaction in the future and, hence, has negative implications for efficiency in the longer-run. Rodriguez for excellent research assistance, Karin Breen for the translation of the experimental instructions and Jos Theelen for writing the software for the experiment. Financial support by the European Union through the TMR research network ENDEAR (FMRX-CT98-0238) is gratefully acknowledged.
Antibodies against acetaldehyde‐modified protein epitopes in human alcoholics

Acetaldehyde, the primary metabolite of ethanol, binds covalently to proteins forming condensation products which have been recently shown to be immunogenic. To assess whether an antibody response against acetaldehyde‐modified protein epitopes is associated with alcoholic liver disease, the serum immunoreactivity against proteins modified in vitro by acetaldehyde and against the corresponding unmodified proteins was measured by an enzyme‐linked immunosorbent assay in 58 alcoholics with varying degrees of liver damage. Alcoholics showed significantly higher titers against protein‐acetaldehyde conjugates than against the unmodified protein, independent of the nature of the carrier protein. The highest titers occurred in alcoholic hepatitis patients. Sera of patients with chronic hepatitis of nonalcoholic origin and of healthy controls also reacted with acetaldehyde conjugates, but their titers were significantly lower than those in alcoholic hepatitis patients. Our data support the idea that binding of acetaldehyde to proteins in humans generates antigenic determinants which trigger a corresponding immune response against such epitopes and suggest that this humoral immune response may be implicated in autoantibody formation and liver damage associated with excessive alcohol consumption.
PRE-SERVICE SECONDARY MATHEMATICS TEACHERS’ UNDERSTANDING OF ABSOLUTE VALUE

This study aims to give a comprehensive account of pre-service secondary mathematics teachers’ understanding of absolute value. Thirty two-item absolute value understanding test was developed and administered to thirty-eight students attending mathematics education department at one private university in Jakarta City, Indonesia. Five of them were selected purposively and interviewed to gain deep information and confirm their written responses in the test. We find that most participants struggled with the absolute value task. There are inconsistencies of the definition of absolute value expressed by them. Besides, typical mistakes made are: (a) removal of absolute value bars; (b) focus heavily on rules; (c) conversion of absolute value bars to parentheses; (d) exclusion of number inside absolute value bars; (e) poor algebraic manipulation; and (f) inability to draw absolute value graph. Based on the findings, the most common cause of mistakes made by the participants is didactical contract in mathematics teaching and learning. Limitation and implications of the study are presented.
Male Victims of Domestic Violence : A Substantive and Methodological Research Review A report to : The Equality Committee of the Department of Education and Science

Domestic violence has emerged as one of the world’s most pressing problems. The United Nations estimates that between 20% to 50% of all women worldwide have experienced physical violence at the hands of an intimate partner or family member. In the United States, more than one million cases of “intimate partner violence” are reported each year, according to the U.S. Department of Justice (Goldberg, 1999, A 16). Stark and Flitcraft (1988) argue that battering is the single most common source of serious injury to women, being responsible for more injuries than road accidents, muggings and rape combined. In 1989, the U.S. Surgeon General also noted that 4,000 women are beaten to death by their partners every year. One of the major platforms for action adopted at the World Conference on Women in Beijing in 1995 was “the prevention and elimination of violence against women and girls. ”
Independent Component Analysis-Based Identification of Covariance Patterns of Microstructural White Matter Damage in Alzheimer’s Disease

The existing DTI studies have suggested that white matter damage constitutes an important part of the neurodegenerative changes in Alzheimer’s disease (AD). The present study aimed to identify the regional covariance patterns of microstructural white matter changes associated with AD. In this study, we applied a multivariate analysis approach, independent component analysis (ICA), to identify covariance patterns of microstructural white matter damage based on fractional anisotropy (FA) skeletonised images from DTI data in 39 AD patients and 41 healthy controls (HCs) from the Alzheimer’s Disease Neuroimaging Initiative database. The multivariate ICA decomposed the subject-dimension concatenated FA data into a mixing coefficient matrix and a source matrix. Twenty-eight independent components (ICs) were extracted, and a two sample t-test on each column of the corresponding mixing coefficient matrix revealed significant AD/HC differences in ICA weights for 7 ICs. The covariant FA changes primarily involved the bilateral corona radiata, the superior longitudinal fasciculus, the cingulum, the hippocampal commissure, and the corpus callosum in AD patients compared to HCs. Our findings identified covariant white matter damage associated with AD based on DTI in combination with multivariate ICA, potentially expanding our understanding of the neuropathological mechanisms of AD.
A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development

Background Evaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large animals are limited. To address this deficiency, we developed a neuropathic pain model in sheep, which shares many anatomical similarities in spine dimensions and cerebrospinal fluid volume as humans. Methods A neuropathic pain state was induced in sheep by tight ligation and axotomy of the common peroneal nerve. The analgesic effect of intrathecal (IT) morphine was investigated. Interspecies comparison was conducted by analyzing the ceiling doses of IT morphine for humans, sheep, and rats. Results Peroneal nerve injury (PNI) produced an 86% decrease in von-Frey filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted for the 8-week test period. Compared to the pre-injury, sham, and contralateral hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED50) for injured PNI hindlimb was 1.8-fold larger and Emax, the dose that produces maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT morphine ceiling dose by allometric scaling. This is in contrast to the approximately 10-fold lower morphine ceiling dose predicted by the rat spinal nerve ligated or spared nerve injury models. Conclusion PNI sheep model has a fast onset and shows stable and long-lasting pain behavioral characteristics. Since the antinociceptive properties of IT morphine are similar to those observed in humans, the PNI sheep model will be a useful tool for the development of analgesics. Its large size and consistent chronic pain behavior will facilitate the development and evaluation of surgical intervention and gene therapy. The PNI sheep pain model provides us with the opportunity for multi-species testing, which will improve the success of clinical trials.
Drug-induced QT prolongation in women during the menstrual cycle.

CONTEXT Women have a higher incidence of torsades de pointes than men, but it is not known if the risk of drug-induced torsades de pointes varies during the menstrual cycle. OBJECTIVES To determine if the degree of QT prolongation in response to ibutilide varies with the menstrual cycle phase and to compare QT prolongation between women and men. DESIGN AND SETTING Cohort study of men and women who received the same intervention conducted between November 1998 and November 2000 at a general clinical research center of a university hospital. PARTICIPANTS A volunteer sample of 58 healthy adults (38 men and 20 women) aged 21 to 40 years. INTERVENTION A low dose of ibutilide (0.003 mg/kg), infused intravenously for 10 minutes. Subjects were monitored for 120 minutes. Women received the intervention on 3 separate occasions to correspond with menstrual cycle phases, which were verified by using hormonal assays. MAIN OUTCOME MEASURE QT interval, recorded from electrocardiogram at timed intervals during and after ibutilide infusion and standardized for variations in heart rate (QTc). RESULTS Maximum (mean [SD]) millisecond increase in QTc after ibutilide infusion was greater for women during menses (63 [13]) and the ovulatory phase (59 [17]) compared with women during the luteal phase (53 [14]) and compared with men (46 [16]; P =.002 vs menses and P =.007 vs ovulation). Progesterone (r = -0.40) and progesterone-to-estradiol ratio (r = -0.41), but not estradiol (r = 0.14) or testosterone (r = 0.09), were inversely correlated with ibutilide-induced QT prolongation. CONCLUSIONS Menstrual cycle and sex differences exist in QTc responses to ibutilide, with the greatest increase in QTc corresponding to the first half of the menstrual cycle.
Induction of cellular and humoral immunological responsiveness to a soluble cercarial antigen preparation from Schistosoma mansoni

The development of immunological responsiveness to a soluble cercarial antigenic preparation (CAP) from Schistosoma mansoni was analyzed in inbred CBA/J mice infected with cercariae, one or multiple times, or sensitized using CAP. Repeated exposure to 75 cercariae at three weekly intervals (3X-75) or subcutaneous administration of 20 mug of CAP (CAP/complete Freund adjuvant [CFA]) stimulated the development of specific anti-CAP lymph node cell blastogenesis. The degree of responsiveness was dependent upon the concentration of CAP in the culture system and was optimal in the dose range of 20 to 30 mug of protein of CAP per culture. Animals exposed once to 75 or 225 cercariae or to two sequential weekly infections with 75 cercariae exhibited a minimal response to CAP in comparison to the responsiveness of 3X-75 or CAP/CFA lymph node cells. Assessment of anti-CAP agglutinating antibody by application of a microtiter passive hemagglutination technique revealed that both 3X-75 and CAP/CFA animals possessed low titers of activity. In addition, both 3X-75 and CAP/CFA sera contained reagin-like antibodies to CAP as detected by the heterologous (rat), 72-h latent period, passive cutaneous anaphylaxis technique.
Splicing localization in motion blurred 3D scenes

We propose a passive forgery detection technique for locating spliced regions in motion blurred images of 3D scenes. We consider general camera motion in hand-held cameras and utilize discrepancies in local motion blur patterns as a cue for splicing detection. We first devise an automatic and computationally efficient scheme to estimate the camera motion using only the blur kernels from authentic region. Next, we utilize the relationship among blur kernels, camera trajectory and local depth to predict a set of authentic blur kernels for any depth map to directly flag spliced regions.
Comparing two tyrosine kinase inhibitors for treatment of advanced renal cell carcinoma in Medicare and commercially insured patients

Abstract Objective: The objective of this study was to compare treatment characteristics, survival and costs for sunitinib and pazopanib for advanced renal cell carcinoma (RCC) in a real-world setting. Methods: Using claims data, this observational, retrospective cohort study selected individuals aged 19 to 89 years, with commercial or Medicare insurance, advanced RCC, and at least one pharmacy claim for sunitinib or pazopanib between 1 November 2009 and 31 December 2012. Treatment characteristics (treatment interruption, adherence, duration and discontinuation), survival, and costs were measured up to 12 months. Statistical models were adjusted for age, gender, geographic region, race, and RxRisk-V score. Results: At baseline, pazopanib patients exhibited significantly worse health status indicators (RxRisk-V score, number of pharmacy claims, and pre-index total healthcare costs) than sunitinib patients. There were no differences in treatment characteristics or survival. Index medication costs (mean difference $5580, p = 0.03, adj p = 0.05) and total healthcare costs (mean difference $12,192, p = 0.09, adj p = 0.07) trended higher with sunitinib. Patients non-adherent with sunitinib incurred significantly higher total costs compared to patients non-adherent with pazopanib (mean difference $17,680, p = 0.04, adj p = 0.01). Conclusions: Mortality data and proxy variables for treatment effectiveness indicate comparable clinical value for both medications. Sunitinib treatment trended towards higher index medication and total healthcare costs despite higher pre-index total costs and worse health status indicators at baseline with pazopanib. Non-adherence with sunitinib was associated with significantly higher total healthcare costs, which may indicate differences in tolerability between the two agents and requires further investigation.
Determinants of students' performance at university: reflections from the caribbean

The study reported upon in this paper examines the performance of a sample of 900 students who graduated in 2004 from the Mona Campus of the University of the West Indies, the largest university in the Anglophone Caribbean region. This analysis of student performance is conducted against the background of considerable changes in the tertiary educational systems, around the world, in general, and in Jamaica and the Caribbean in particular. These changes are requiring universities to place much greater emphasis on self-study, and on ensuring that they are performing efficiently in all areas, including the area of student transformation, which is an area of performance linked, at least in part, to academic results. The study, relying on statistical analysis, identified five factors as important determinants of student performance: gender, which is the area of most intense study in the Caribbean in relation to student performance; enrolment status; faculty of study; on versus off campus residence; and whether students did or did not apply for financial assistance. The paper concludes with implications from the study’s findings.