LLukas22/scidocs huggingface dataset:
Steady-state pharmacokinetic comparison of generic and branded formulations of stavudine, lamivudine and nevirapine in HIV-infected Ugandan adults.

BACKGROUND
We aimed to compare the steady-state pharmacokinetic parameters and tolerability of Triomune 40 (stavudine 40 mg, lamivudine 150 mg and nevirapine 200 mg) and branded formulations of these drugs in HIV-infected Ugandans.


METHODS
This includes a randomized, open-label, cross-over study of HIV-infected patients stable on therapy for 1 month. Patients were randomized to generic or branded formulation. Plasma pharmacokinetics were assessed after 1 month. The following day, alternate formulation was administered, and 1 month later, drug pharmacokinetics were re-assessed. Plasma pharmacokinetics were determined using HPLC-UV detection. Similarity between steady-state pharmacokinetic parameters was assessed using the US Food and Drug Administration standards for bioequivalency testing. Tolerability was assessed using questionnaires.


RESULTS
Sixteen (10 females) patients completed the study. Median (IQR) age, weight and CD4 count were 37 (33.7-40) years, 65 (63.4-66) kg and 292 (220.7-344.5) cells/mm(3), respectively. All patients received co-trimoxazole. The geometric mean ratio (90% CI) for stavudine, lamivudine and nevirapine was 0.92 (0.78-1.08), 1.11 (0.95-1.30) and 0.84 (0.64-1.11), respectively, for C(max), and 0.83 (0.70-0.97), 1.06 (0.94-1.20) and 0.88 (0.71-1.10), respectively, for AUC. Stavudine plasma concentrations were significantly lower for the generic formulation. Pharmacokinetic parameter inter-individual variability ranged from 29% to 99%. There were no differences in tolerability for the two formulations.


CONCLUSIONS
Pharmacokinetic profiles of generic and branded drugs were similar. Differences particularly with regard to stavudine were demonstrated. Surveillance of the quality of generic antiretroviral drugs in the target populations is needed. Capacity building for pharmacokinetic research in resource-limited settings is a priority.
Dyadosphere bending of light

In the context of the static and spherically symmetric solution of a charged compact object, we present the expression for the bending of light in the region just outside the event horizon -the dyadosphere -where vacuum polarization effects are taken into account.
Left ventricular electromechanical mapping to assess efficacy of phVEGF(165) gene transfer for therapeutic angiogenesis in chronic myocardial ischemia.

BACKGROUND
NOGA left ventricular (LV) electromechanical mapping (EMM) can be used to distinguish among infarcted, ischemic, and normal myocardium. We investigated the use of percutaneous LV EMM to assess the efficacy of myocardial gene transfer (GTx) of naked plasmid DNA encoding for vascular endothelial growth factor (phVEGF(165)), administered during surgery by direct myocardial injection in patients with chronic myocardial ischemia.


METHODS AND RESULTS
A total of 13 consecutive patients (8 men, mean age 60.1+/-2. 3 years) with chronic stable angina due to angiographically documented coronary artery disease, all of whom had failed conventional therapy (drugs, PTCA, and/or CABG), were treated with direct myocardial injection of phVEGF(165) via a minithoracotomy. Foci of ischemic myocardium were identified on LV EMM by preserved viability associated with an impairment in linear local shortening. Myocardial viability, defined by mean unipolar and bipolar voltage recordings >/=5 and >/=2 mV, respectively, did not change significantly after GTx. Analysis of linear local shortening in areas of myocardial ischemia, however, disclosed significant improvement after (15.26+/-0.98%) versus before (9.94+/-1.53%, P:=0. 004) phVEGF(165) GTx. The area of ischemic myocardium was consequently reduced from 6.45+/-1.37 cm(2) before GTx to 0.95+/-0. 41 cm(2) after GTx (P:=0.001). These findings corresponded to improved perfusion scores calculated from single-photon emission CT-sestamibi myocardial perfusion scans recorded at rest (7.4+/-2.1 before GTx versus 4.5+/-1.4 after GTx, P:=0.009) and after pharmacological stress (12.8+/-2.7 before GTx versus 8.5+/-1.7 after GTx, P:=0.047).


CONCLUSIONS
The results of EMM constitute objective evidence that phVEGF(165) GTx augments perfusion of ischemic myocardium. These findings, together with reduction in the size of the defects documented at rest by serial single-photon emission CT-sestamibi imaging, suggest that phVEGF(165) GTx may successfully rescue foci of hibernating myocardium.
Context-aware Argument Mining and Its Applications in Education

CONTEXT-AWARE ARGUMENT MINING AND ITS APPLICATIONS IN EDUCATION
Multilateral Organizations as Morally Response‐Able

Global Poverty, Ethics and Human Rights: The Role of Multilateral Organisations. By Desmond McNeill, Asuncion Lera St. Clair. New York: Routledge, 2009. 192 pp., $39.95 paperback (ISBN-13: 978-0-415-44594-8).

Who is responsible for the persistence of extreme poverty in the world? International organizations (IO) are, according to the authors of Global Poverty, Ethics and Human Rights , not necessarily because they have caused it (although in some cases they have contributed to the conditions of extreme poverty) but because they are mandated to ameliorate conditions of extreme poverty. And yet, they fail. Why is this the case? The answer to this question is found in the analysis of four case studies. These cases include two of the perhaps most important global development organizations, the World Bank (WB) and the United Nations Development Program (UNDP), as well as two less studied IOs, the United Nations Educational Scientific and Cultural Organization (UNESCO) and the Inter-American Development Bank (IDB).

This is an ambitious comparative study about discourse (or lack thereof) within IOs on ethics and human rights as it relates to poverty. Building on the authors' earlier scholarship on ideas and material resources as influences on multilateral organizations, the book addresses the ethical and moral dimension of IOs. At the heart of it is the issue of global justice and the role played by IOs in responding to it. The authors ask “Why cannot organizations with global scope and global mandate—such as the World Bank and the UNDP—more explicitly act, and be proud to act, as promoters of global justice?” One major obstacle, according to the authors, is resistance by state governments within these organizations; thus, the structure of the IOs poses a hindrance to bringing about global justice.

While the book is structured so that each chapter analyzing the cases can be read independently (thus, enabling the reader interested in only one or two cases to go straight to the source), the comparative analysis (although not systematically uniform) of several IOs …
Phase II trial of the histone deacetylase inhibitor romidepsin in patients with recurrent/metastatic head and neck cancer.

OBJECTIVES
Patients with advanced squamous cell carcinoma of the head and neck (SCCHN) have limited treatment options. Inhibition of histone deacetylases (HDACs) represents a novel therapeutic approach warranting additional investigation in solid tumors.


METHODS
A phase II trial of single agent romidepsin, an HDAC inhibitor, was performed in 14 patients with SCCHN who provided consent for pre- and post-therapy samples of accessible tumor, blood and uninvolved oral mucosa. Romidepsin was administered at 13 mg/m(2) as a 4-h intravenous infusion on days 1, 8 and 15 of 28 day cycles, with response assessment by RECIST every 8 weeks.


RESULTS
Objective responses were not observed, although 2 heavily pretreated patients had brief clinical disease stabilization. Observed toxicities were expected, including frequent severe fatigue. Immunohistochemical analysis of 7 pre- and post-treatment tumor pairs demonstrated induction of p21(Waf1/Cip1) characteristic of HDAC inhibition, as well as decreased Ki67 staining. Exploratory microarray analyses of mucosal and tumor samples detected changes in gene expression following romidepsin treatment that were most commonly associated with regulation of transcription, cell cycle control, signal transduction, and electron transport. Treatment with romidepsin did not alter the extent of DNA methylation of candidate gene loci (including CDH1 and hMLH1) in SCCHN tumors.


CONCLUSIONS
Single agent romidepsin has limited activity for the treatment of SCCHN but can effectively achieve tumor-associated HDAC inhibition. Although tolerability of romidepsin in this setting may be limiting, further evaluation of other HDAC inhibitors in combination with active therapies may be justified.
Acute effects of instrument assisted soft tissue mobilization for improving posterior shoulder range of motion in collegiate baseball players.

BACKGROUND
Due to the repetitive rotational and distractive forces exerted onto the posterior shoulder during the deceleration phase of the overhead throwing motion, limited glenohumeral (GH) range of motion (ROM) is a common trait found among baseball players, making them prone to a wide variety of shoulder injuries. Although utilization of instrument-assisted soft tissue mobilization (IASTM), such as the Graston® Technique, has proven effective for various injuries and disorders, there is currently no empirical data regarding the effectiveness of this treatment on posterior shoulder tightness.


PURPOSE
To determine the effectiveness of IASTM in improving acute passive GH horizontal adduction and internal rotation ROM in collegiate baseball players.


METHODS
Thirty-five asymptomatic collegiate baseball players were randomly assigned to one of two groups. Seventeen participants received one application of IASTM to the posterior shoulder in between pretest and posttest measurements of passive GH horizontal adduction and internal rotation ROM. The remaining 18 participants did not receive a treatment intervention between tests, serving as the controls. Data were analyzed using separate 2× 2 mixed-model analysis of variance, with treatment group as the between-subjects variable and time as the within-subjects variable.


RESULTS
A significant group-by-time interaction was present for GH horizontal adduction ROM with the IASTM group showing greater improvements in ROM (11.1°) compared to the control group (-0.12°) (p <0.001). A significant group-by-time interaction was also present for GH internal rotation ROM with the IASTM group having greater improvements (4.8°) compared to the control group (-0.14°) (p < 0.001).


CONCLUSIONS
The results of this study indicate that an application of IASTM to the posterior shoulder provides acute improvements in both GH horizontal adduction ROM and internal rotation ROM among baseball players.


LEVEL OF EVIDENCE
2b.
Does Influenza Vaccination Modify Influenza Severity? Data on Older Adults Hospitalized With Influenza During the 2012-2013 Season in the United States.

BACKGROUND
Some studies suggest that influenza vaccination might be protective against severe influenza outcomes in vaccinated persons who become infected. We used data from a large surveillance network to further investigate the effect of influenza vaccination on influenza severity in adults aged ≥50 years who were hospitalized with laboratory-confirmed influenza.


METHODS
We analyzed influenza vaccination and influenza severity using Influenza Hospitalization Surveillance Network (FluSurv-NET) data for the 2012-2013 influenza season. Intensive care unit (ICU) admission, death, diagnosis of pneumonia, and hospital and ICU lengths of stay served as measures of disease severity. Data were analyzed by multivariable logistic regression, parametric survival models, and propensity score matching (PSM).


RESULTS
Overall, no differences in severity were observed in the multivariable logistic regression model. Using PSM, adults aged 50-64 years (but not other age groups) who were vaccinated against influenza had a shorter length of ICU stay than those who were unvaccinated (hazard ratio for discharge, 1.84; 95% confidence interval, 1.12-3.01).


CONCLUSIONS
Our findings show a modest effect of influenza vaccination on disease severity. Analysis of data from seasons with different predominant strains and higher estimates of vaccine effectiveness are needed.
Collaboration in Augmented Reality

Augmented Reality (AR) is a technology that allows users to view and interact in real time with virtual images seamlessly superimposed over the real world. AR systems can be used to create unique collaborative experiences. For example, co-located users can see shared 3D virtual objects that they interact with, or a user can annotate the live video view of a remote worker, enabling them to collaborate at a distance. The overall goal is to augment the face-to-face collaborative experience, or to enable remote people to feel that they are virtually co-located. In this special issue on collaboration in augmented reality, we begin with the visions of science fiction authors of future technologies that might significantly improve collaboration, then introduce research articles which describe progress towards these visions, finally we outline a research agenda discussing the work still to be done.
Metyrapone as additive treatment in major depression: a double-blind and placebo-controlled trial.

BACKGROUND
Inhibitors of steroid synthesis have been reported to exert antidepressive effects, according to preliminary findings.


OBJECTIVE
To test whether the addition of metyrapone to standard antidepressants induces a more rapid, more efficacious, and sustained treatment response in patients with major depression.


DESIGN
Double-blind, randomized, placebo-controlled trial.


SETTING
Hospitalized care.


PATIENTS
Sixty-three inpatients with a DSM-IV diagnosis of major depression and a baseline score 18 points or higher on the Hamilton Rating Scale for Depression.


INTERVENTIONS
Random allocation to 2 treatment groups receiving either placebo or metyrapone (1 g/d) for the first 3 weeks during a 5-week treatment with standard serotonergic antidepressants (nefazodone or fluvoxamine).


MAIN OUTCOME MEASURES
Primary outcome criteria were the number of responders and the time to onset of action. Responder rates were considered twice after 3 and 5 weeks with a definition of treatment response as 30% and 50% reduction, respectively, of baseline Hamilton Rating Scale for Depression scores. Onset of action was defined as the time point at which at least a 20% reduction of baseline Hamilton Rating Scale for Depression scores occurred.


RESULTS
Using intention-to-treat analysis, we found that a higher proportion of patients receiving metyrapone showed a positive treatment response at day 21 (23 of 33 patients) and at day 35 (19 of 33 patients) compared with placebo patients (day 21: 13 of 30 patients; Fisher exact P = .031; day 35: 10 of 30 patients; Fisher exact P = .047). The clinical course of patients treated with metyrapone showed an earlier onset of action (Kaplan-Meier analysis; log-rank test P<.006) beginning in the first week. The plasma concentrations of corticotropin and deoxycortisol were significantly higher during metyrapone treatment (multivariate analysis of covariance, P<.05), whereas cortisol remained largely unchanged. Metyrapone treatment was well tolerated without serious adverse effects.


CONCLUSIONS
Metyrapone is an effective adjunct in the treatment of major depression, accelerating the onset of antidepressant action. A better treatment outcome compared with standard treatment and a sustained antidepressive effect were observed.
Sleep related problems and urological symptoms: testing the hypothesis of bidirectionality in a longitudinal, population based study.

PURPOSE
We evaluate the bidirectional association between urological symptoms (urinary incontinence, lower urinary tract symptoms and nocturia) and sleep related variables.


MATERIALS AND METHODS
Data were obtained from a prospective cohort study of 1,610 men and 2,535 women who completed baseline (2002 to 2005) and followup (2006 to 2010) phases of the BACH (Boston Area Community Health) Survey, a population based random sample survey. Sleep restriction (5 hours or less per night), restless sleep, sleep medication use and urological symptoms were assessed by self-report. Urinary incontinence was defined as weekly leakage or moderate/severe leakage, lower urinary tract symptoms (overall, obstructive, irritative) were defined by the AUA-SI (American Urological Association symptom index) and nocturia was defined as urinary frequency 2 or more times per night.


RESULTS
At the 5-year followup 10.0%, 8.5% and 16.0% of subjects newly reported lower urinary tract symptoms, urinary incontinence and nocturia, respectively, and 24.2%, 13.3% and 11.6% newly reported poor sleep quality, sleep restriction and use of sleep medication, respectively. Controlling for confounders, the odds of urological symptoms developing were consistently increased for subjects who reported poor sleep quality and sleep restriction at baseline, but only baseline nocturia was positively associated with incident sleep related problems at followup. Body mass index, a potential mediator, reduced selected associations between sleep and incident urinary incontinence and irritative symptoms, but C-reactive protein did not.


CONCLUSIONS
These data suggest that self-reported sleep related problems and urological symptoms are linked bidirectionally, and that body mass index may be a factor in the relationship between sleep and the development of urological symptoms.
Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial.

AIMS
This study investigated the efficacy and tolerability of empagliflozin as add-on to pioglitazone ± metformin in patients with type 2 diabetes (T2DM).


METHODS
Patients with HbA1c ≥7 and ≤10% were randomized and treated with once daily empagliflozin 10 mg (n = 165), empagliflozin 25 mg (n = 168) or placebo (n = 165) as add-on to pioglitazone ± metformin for 24 weeks. Endpoints included changes from baseline in HbA1c (primary endpoint), fasting plasma glucose (FPG) and body weight at week 24.


RESULTS
Adjusted mean ± standard error changes in HbA1c were -0.6 ± 0.07% and -0.7 ± 0.07% with empagliflozin 10 mg and 25 mg, respectively, vs. -0.1 ± 0.07% with placebo (both p < 0.001). More patients with HbA1c ≥7% at baseline achieved HbA1c <7% with empagliflozin 10 mg (23.8%) and 25 mg (30.0%) vs. placebo (7.7%) (both p < 0.001). FPG decreased with empagliflozin (-0.94 mmol/l for 10 mg and -1.22 mmol/l for 25 mg) and increased with placebo (+0.36 mmol/l; both p < 0.001). Adjusted mean ± standard error changes in weight were -1.62 ± 0.21 kg and -1.47 ± 0.21 kg with empagliflozin 10 mg and 25 mg, respectively, vs. +0.34 ± 0.21 kg with placebo (both p < 0.001). Similar proportions of patients reported adverse events with empagliflozin (67.3-71.4%) and placebo (72.7%). Confirmed hypoglycaemia was reported by 1.2-2.4% of patients on empagliflozin and 1.8% on placebo.


CONCLUSION
Empagliflozin 10 mg and 25 mg once daily for 24 weeks as add-on to pioglitazone ± metformin reduced HbA1c, FPG and weight and were well tolerated in patients with T2DM.
Chapter 3 The Dog as a Model for Understanding Human Social Behavior

This chapter was originally published in the book Advances in The Study of Behavior, Vol. 39, published by Elsevier, and the attached copy is provided by Elsevier for the author's benefit and for the benefit of the author's institution, for non-commercial research and educational use including without limitation use in instruction at your institution, sending it to specific colleagues who know you, and providing a copy to your institution’s administrator.
Palliative radiotherapy for patients with tracheobronchial and esophageal compression due to intrathoracic malignant tumors.

AIMS
To evaluate palliative outcomes of patients with extrinsic malignant tracheobronchial or esophageal stenosis treated with radiation. Mediastinal or hilar lymphadenopathy surrounding the tracheobronchi or esophagus may cause compression, presenting as dyspnea and dysphagia respectively. Treatment is important for symptom relief and maintaining patients' quality of life.


METHODS
Dyspnea and dysphagia were assessed using the Hugh-Jones score and a modified dysphagia scale, respectively. A total of 13 patients (median age, 60 years) with dyspnea received palliative radiotherapy. The primary organs were lung (n = 6), colorectum (n = 5), hypopharynx (n = 1) and uterine cervix (n = 1). Three patients received concurrent chemotherapy. The median time-adjusted biological effective dose (BED) was 33.0 Gy(10) . Ten patients (median age, 61) with dysphagia received palliative radiotherapy. The primary organs were lung (n = 7), esophagus (n = 2) and hypopharynx (n = 1). Three patients received concurrent chemotherapy. The median time-adjusted BED was 32.1 Gy(10) .


RESULTS
Palliation of dyspnea and dysphagia occurred in seven (54%) and five (50%) patients, respectively. Patients treated with doses over 35 Gy(10) had greater score improvements than those treated with less than 35 Gy(10) in both groups. Patients who received concurrent chemoradiotherapy had greater score improvements than those treated with radiotherapy alone. Dyspnea patients with pretreatment scores of 2 (n = 5) had greater score improvements than those with scores of 3 or more (n = 8).


CONCLUSION
External beam radiotherapy should be considered for patients with tracheobronchial or esophageal stenosis before their symptoms worsen. The prescription dose should be over 35 Gy(10) .