LLukas22/scidocs huggingface dataset:
Small is Beautiful : Preferential Trade Agreements and The Impact of Country Size , Market Share , Efficiency and Trade Policy

1668 The smaller the volume (or share) of imports from the trading partner, the larger the impact of a preferential trade agreement on home country welfare—because the smaller the imports, the smaller the loss in tariff revenue. And the home country is better off as a small member of a large bloc than as a large member of a small bloc. Summary findings There has been a resurgence of preferential trade agreements (PTAs) partly because of the deeper European integration known as EC-92, which led to a fear of a Fortress Europe; and partly because of the U.S. decision to form a PTA with Canada. As a result, there has been a domino effect: a proliferation of PTAs, which has led to renewed debate about how PTAs affect both welfare and the multilateral system. Schiff examines two issues: the welfare impact of preferential trade agreements (PTAs) and the effect of structural and policy changes on PTAs. He asks how the PTA's effect on home-country welfare is affected by higher demand for imports; the efficiency of production of the partner or rest of the world (ROW); the share imported from the partner (ROW); and the initial protection on imports from the partner (ROW). Among his findings: • An individual country benefits more from a PTA if it imports less from its partner countries (with imports measured either in volume or as a share of total imports). This result has important implications for choice of partners. • A small home country loses from forming a free trade agreement (FTA) with a small partner country but gains from forming one with the rest of the world. In other words, the home country is better off as a small member of a large bloc than as a large member of a small bloc. This result need not hold if smuggling is a factor. • Home country welfare after formation of a FTA is higher when imports from the partner country are smaller, whether the partner country is large or small. Welfare worsens as imports from the partner country increase. • In general, a PTA is more beneficial (or less harmful) for a country with lower import demand. A PTA is also more beneficial for a country with a more efficient import-substituting sector, as this will result in a lower demand for imports. • A small country may gain from forming a PTA when smuggling …
The effectiveness of pulsed electrical stimulation (E-PES) in the management of osteoarthritis of the knee: a protocol for a randomised controlled trial

BACKGROUND
Osteoarthritis (OA) of the knee is one of the main causes of musculoskeletal disability in the western world. Current available management options provide symptomatic relief (exercise and self-management, medication and surgery) but do not, in general, address the disease process itself. Moreover, adverse effects and complications with some of these interventions (medication and surgery) and the presence of co-morbidities commonly restrict their use. There is clearly a need to investigate treatments that are more widely applicable for symptom management and which may also directly address the disease process itself. In two randomised controlled trials of four and 12 weeks duration, pulsed electrical stimulation was shown to be effective in managing the symptoms of OA of the knee. Laboratory and animal studies demonstrate the capacity of externally applied electric and electromagnetic fields to positively affect chondrocyte proliferation and extracellular matrix protein production. This latter evidence provides strong theoretical support for the use of electrical stimulation to maintain and repair cartilage in the clinical setting and highlights its potential as a disease-modifying modality.


METHODS/DESIGN
A double-blind, randomised, placebo-controlled, repeated measures trial to examine the effectiveness of pulsed electrical stimulation in providing symptomatic relief for people with OA of the knee over 26 weeks. Seventy people will be recruited and information regarding age, gender, body mass index and medication use will be recorded. The population will be stratified for age, gender and baseline pain levels. Outcome measures will include pain (100 mm VAS and WOMAC 3.1), function (WOMAC 3.1), stiffness (WOMAC 3.1), patient global assessment (100 mm VAS) and quality of life (SF-36). These outcomes will be measured at baseline, four, 16 and 26 weeks. Activity levels will be measured at baseline and 16 weeks using accelerometers and the Human Activity Profile questionnaire. A patient global perceived effect scale (11-point Likert) will be completed at 16 and 26 weeks.


DISCUSSION
This paper describes the protocol for a randomised, double-blind, placebo-controlled trial that will contribute to the evidence regarding the use of sub-sensory pulsed electrical stimulation in the management of OA of the knee.


TRIAL REGISTRATION
Australian Clinical Trials Registry ACTRN12607000492459.
Dapagliflozin Monotherapy in Type 2 Diabetic Patients With Inadequate Glycemic Control by Diet and Exercise

OBJECTIVE
Dapagliflozin, a highly selective inhibitor of the renal sodium-glucose cotransporter-2, increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner. We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes.


RESEARCH DESIGN AND METHODS
This was a 24-week parallel-group, double-blind, placebo-controlled phase 3 trial. Patients with A1C 7.0-10% (n = 485) were randomly assigned to one of seven arms to receive once-daily placebo or 2.5, 5, or 10 mg dapagliflozin once daily in the morning (main cohort) or evening (exploratory cohort). Patients with A1C 10.1-12% (high-A1C exploratory cohort; n = 73) were randomly assigned 1:1 to receive blinded treatment with a morning dose of 5 or 10 mg/day dapagliflozin. The primary end point was change from baseline in A1C in the main cohort, statistically tested using an ANCOVA.


RESULTS
In the main cohort, mean A1C changes from baseline at week 24 were -0.23% with placebo and -0.58, -0.77 (P = 0.0005 vs. placebo), and -0.89% (P < 0.0001 vs. placebo) with 2.5, 5, and 10 mg dapagliflozin, respectively. Signs, symptoms, and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms. There were no major episodes of hypoglycemia. Data from exploratory cohorts were consistent with these results.


CONCLUSIONS
Dapagliflozin lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes. The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes.
Plasma Fetuin-A Levels and the Risk of Type 2 Diabetes

OBJECTIVE
The liver-secreted protein fetuin-A induces insulin resistance in animals, and circulating fetuin-A is elevated in insulin resistance and fatty liver in humans. We investigated whether plasma fetuin-A levels predict the incidence of type 2 diabetes in a large prospective, population-based study.


RESEARCH DESIGN AND METHODS
A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 27,548 subjects was designed. We randomly selected a subcohort of 2,500 individuals of whom 2,164 were diabetes free at baseline and had anamnestic, anthropometrical, and metabolic data for analysis. Of the 849 incident diabetic case subjects identified in the full cohort during 7 years of follow-up, 703 remained for analyses after similar exclusions.


RESULTS
Plasma fetuin-A levels were positively associated with diabetes risk after adjustment for age (relative risk [RR] for extreme quintiles 1.75 [95% CI 1.32-2.31]; RR for 10 mug/ml 1.04 [1.03-1.06]). The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 mug/ml 1.03 [1.01-1.06]). Adjustment for glucose, triglycerides, HDL cholesterol, A1C, gamma-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 mug/ml full adjusted model 1.05 [1.02-1.07]). Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose.


CONCLUSIONS
Our data suggest that fetuin-A is an independent risk factor of type 2 diabetes.
Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity.

PURPOSE
Mixed bacterial vaccine (MBV, Coley's toxins) is a historical, vaguely defined preparation of heat-inactivated Streptococcus pyogenes and Serratia marcescens used as nonspecific immunotherapy in the treatment of cancer. The mechanism of action is suspected to have an immunologic basis, yet it is poorly defined up to now. We developed a new, biochemically well defined and current good manufacturing practice-compliant MBV preparation, which has been investigated in patients with NY-ESO-1 expressing cancers.


EXPERIMENTAL DESIGN
Patients received MBV subcutaneously at a starting dose of 250 EU (endotoxin units) twice a week. The MBV dose was escalated in each patient until a body temperature of 38°C to 39.5°C was induced or up to the maximum dose of 547.000 EU. Changes in serum cytokine levels were determined and immune responses to NY-ESO-1 were evaluated. Tumor response was assessed according to RECIST.


RESULTS
Twelve patients were enrolled and 11 of them developed fever after the administration of MBV. Ten of 12 patients showed a consistent increase in serum IL-6 levels with the highest levels coinciding with the highest body temperature. A subgroup of patients showed increasing levels of TNF-α, IFN-γ, and IL1-β. A patient with metastatic bladder cancer showed a partial tumor response strongly correlated with MBV-induced fever and highly elevated levels of several cytokines.


CONCLUSIONS
MBV at fever-inducing dose levels can lead to a massive induction of immunoregulatory cytokines that may be involved in inducing tumor regressions. We propose to further explore the role of MBV as a potent immune modulator at higher dose levels and in conjunction with antigen-specific cancer vaccines.
The Metaphorical Concept “ Life is a Journey ” in the Qur ’ an : a Cognitive-semantic Analysis

This paper demonstrates how the conceptual metaphor “life is a journey” pervades the Qur’an and how within the same scope we can find some related metaphors, such as “the Straight Way”, “the way of Hell” and “Companions of the Fire”, among others. The metaphor “life is a journey” takes as a source domain the concept “journey” and as a target domain the concept “life”. The other related metaphors are an extension of that metaphor. The instances of the “journey” metaphor with its underlying “path” schema will be analyzed using the Cognitive Theory of Metaphor as created by Lakoff and Johnson (1980) and developed later by Lakoff and Turner (1989), and others, e.g. Wreth (1994, 1999). The application of the Cognitive Theory of Metaphor will reveal how this metaphor is used creatively, as it is built on dichotomy or contrast, and how it is widened to cover a broader aspect of life, i.e., life after physical death (the afterlife/hereafter). Meanwhile, the tenets of the theory will be confirmed by experimenting them with the Qur’anic metaphors to show how they are a most effective tool for conducting such an analysis. Der vorliegende Beitrag zeigt, wie sich die Konzeptmetapher „Leben ist Reise“ durch den Koran zieht und inwiefern dort weitere ähnliche Metaphern wie z.B. „der direkte Weg“, „der Weg der Hölle“ und „die Gefährten des Feuers“ auftreten. Die Metapher „Leben ist Reise“ hat das Konzept „Reise“ als Quellbereich und das Konzept „Leben“ als Zielbereich. Die anderen damit in Verbindung stehenden Metaphern stellen eine Fortführung der Metapher dar. Die Beispiele der Reise-Metapher mit dem ihnen zugrundeliegenden „Weg-Schema“ werden mit Hilfe der von Lakoff/Johnson (1980) begründeten und von Lakoff/Turner (1989), sowie Wreth (1994, 1999) weiterentwickelten kognitiven Metapherntheorie (Lakoff / Johnson, 1980) analysiert. Die Anwendung der kognitiven Metapherntheorie zeigt, inwiefern die Reisemetapher auf kreative Weise verwendet wird, insofern als sie auf Dichotomie oder Kontrast beruht, und wie sie sich auf einen sehr weit gefassten Begriff des Lebens, d.h. auch das Leben nach dem Tod (das Jenseits) umfassend, beziehen lässt. Durch das Experimentieren mit den Metaphern des Koran wird bestätigt, dass die verwendete Theorie ein äußerst effektives Analysewerkzeug darstellt.
Intradermal vs intramuscular vaccine against hepatitis B infection in dialysis patients: a meta-analysis of randomized trials.

Chronic dialysis patients are at risk of contracting hepatitis B virus infection and have a diminished immune response to hepatitis B virus vaccine. Recent reports support intradermal administration of hepatitis B virus vaccine in patients on regular dialysis but the efficacy and safety of this approach remain unclear. We conducted a meta-analysis of randomized, controlled clinical trials to compare seroprotection achieved by intradermal vs intramuscular hepatitis B vaccine, in patients on maintenance dialysis. Meta-analysis of data from 718 adults (14 trials) on long-term dialysis demonstrated that intramuscular hepatitis B vaccination was less likely to achieve seroprotection than intradermal vaccination, the pooled odds ratio was 0.454 (95% CI, 0.3; 0.67), P = 0.001. The test of study heterogeneity was not significant. This difference did not persist during follow-up (6-60 months after completing vaccine schedule), the pooled odds ratio being 0.718 (95% CI, 0.36; 1.47), NS. Some evidence of significant heterogeneity including publication bias was present but stratified analysis in various subgroups showed that this issue did not meaningfully change our results. Intradermal hepatitis B vaccine was safe and well tolerated. We conclude that intradermal hepatitis B vaccine induces a superior response rate compared to intramuscular route at completion of vaccine cycle, despite a lower vaccine dose. No significant advantage was found over longer follow-up. It remains unclear whether the higher seroprotection rate achieved with intradermal route translates into a lower frequency of de novo hepatitis B among patients on maintenance dialysis.
Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial.

BACKGROUND
Dacomitinib is an irreversible pan-EGFR family tyrosine kinase inhibitor. Findings from a phase 2 study in non-small cell lung cancer showed favourable efficacy for dacomitinib compared with erlotinib. We aimed to compare dacomitinib with erlotinib in a phase 3 study.


METHODS
In a randomised, multicentre, double-blind phase 3 trial in 134 centres in 23 countries, we enrolled patients who had locally advanced or metastatic non-small-cell lung cancer, progression after one or two previous regimens of chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and presence of measurable disease. We randomly assigned patients in a 1:1 ratio to dacomitinib (45 mg/day) or erlotinib (150 mg/day) with matching placebo. Treatment allocation was masked to the investigator, patient, and study funder. Randomisation was stratified by histology (adenocarcinoma vs non-adenocarcinoma), ethnic origin (Asian vs non-Asian and Indian sub-continent), performance status (0-1 vs 2), and smoking status (never-smoker vs ever-smoker). The coprimary endpoints were progression-free survival per independent review for all randomly assigned patients, and for all randomly assigned patients with KRAS wild-type tumours. The study has completed accrual and is registered with ClinicalTrials.gov, number NCT01360554.


FINDINGS
Between June 22, 2011, and March 12, 2013, we enrolled 878 patients and randomly assigned 439 to dacomitinib (256 KRAS wild type) and 439 (263 KRAS wild type) to erlotinib. Median progression-free survival was 2·6 months (95% CI 1·9-2·8) in both the dacomitinib group and the erlotinib group (stratified hazard ratio [HR] 0·941, 95% CI 0·802-1·104, one-sided log-rank p=0·229). For patients with wild-type KRAS, median progression-free survival was 2·6 months for dacomitinib (95% CI 1·9-2·9) and erlotinib (95% CI 1·9-3·0; stratified HR 1·022, 95% CI 0·834-1·253, one-sided p=0·587). In patients who received at least one dose of study drug, the most frequent grade 3-4 adverse events were diarrhoea (47 [11%] patients in the dacomitinib group vs ten [2%] patients in the erlotinib group), rash (29 [7%] vs 12 [3%]), and stomatitis (15 [3%] vs two [<1%]). Serious adverse events were reported in 52 (12%) patients receiving dacomitinib and 40 (9%) patients receiving erlotinib.


INTERPRETATION
Irreversible EGFR inhibition with dacomitinib was not superior to erlotinib in an unselected patient population with advanced non-small-cell lung cancer or in patients with KRAS wild-type tumours. Further study of irreversible EGFR inhibitors should be restricted to patients with activating EGFR mutations.


FUNDING
Pfizer.
Connecting usability education and research with industry needs and practices

Ideally, academic research should inform workplace practices and workplace practices should inform academic research and education. However, as many researchers have noted, a gap often exists between academia and industry. This article begins to bridge that gap by reporting the results of a small-scale study at Microsoft in which 12 individuals were interviewed about their views on usability education and research. This study addressed two questions: (1) What knowledge, skills, and abilities should technical communication teachers stress in teaching usability and (2) how can academic research in usability benefit practitioners? The results indicate that usability education needs to be expanded to include additional usability evaluation methods and that students need strong critical assessment and communication skills when they enter the workplace. The results also reveal that usability research in the areas of return-on-investment, online help, and cognition would be of great use to practitioners.
Managerial coping with organizational change: A dispositional perspective.

In a departure from the organizational development literature, this study hypothesized that managerial responses to organizational change are influenced by 7 dispositional traits (locus of control, generalized self-efficacy, self-esteem, positive affectivity, openness to experience, tolerance for ambiguity, and risk aversion). Data were collected from 6 organizations (N = 514) to test the hypotheses. The 7 traits were reduced to 2 factors: Positive Self-Concept and Risk Tolerance. Both of these trait factors significantly predicted self-reports and independent assessments of coping with change. Results also indicated that coping with organizational change was related to extrinsic (salary, job level, plateauing, job performance) and intrinsic (organizational commitment, job satisfaction) career outcomes and that coping mediated roughly half of the relationships between the dispositional factors and these career outcomes.
A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

OBJECTIVES:
To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator.


METHODS:
This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade.


RESULTS:
The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety.


CONCLUSION:
The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯).
A randomized controlled trial for improving patient self-assessment of synovitis in rheumatoid arthritis with education by ultrasonography: the RAEUS Study.

OBJECTIVE
Patients can potentially monitor disease activity of RA through self-assessed swollen joints (clinical synovitis), but reliability is poor. The objective is to evaluate the use of education by US feedback on the ability of patients to assess for clinical synovitis in RA.


METHODS
We performed a 6 month, single-centre, randomized controlled trial on patients with established RA to study the effect of education on self-assessment of joints that included initial brief patient training on tender (TJC) and swollen (SJC) joint counts followed by US feedback every 3 months vs standard care without education. Patient and physician independently performed 28-joint counts at each visit. Outcome variables included the percentage of patients with good agreement with physician-derived swollen joints [prevalence-adjusted bias-adjusted kappa (PABAK) >0.6] as well as agreement in the SJC (Bland and Altman 95% limits of agreement), feasibility/patient satisfaction survey and disease activity at 6 months.


RESULTS
Of the 101 randomized patients, 95 were included (51 in the education arm and 44 in the standard care arm). At 6 months there was a significant difference in the proportion of patients with swollen joint PABAK >0.6 in the education arm compared with standard care (98 vs 85%, P = 0.02). Limits of agreement for the SJC difference between physician and patients were reduced only in the education arm. The training method is considered feasible, with 94% of patients reporting it as useful. A trend of higher rates of disease remission (28-joint DAS <2.6) in the education arm vs standard care (47% vs 29%, P = 0.07) was seen.


CONCLUSION
A short course of education with US feedback may be helpful in educating patients to assess for clinical synovitis.


TRIAL REGISTRATION
Clinical trials.gov, https://clinicaltrials.gov, NCT02351401.
Efficacy and safety of flexible-dose oral sildenafil citrate (Viagra®) in the treatment of erectile dysfunction in Brazilian and Mexican men

A 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of flexible-dose sildenafil citrate (Viagra®) treatment (25, 50 or 100 mg) in Brazilian and Mexican men with erectile dysfunction (ED) of broad-spectrum etiology. Efficacy was assessed on the basis of responses to the 15-item International Index of Erectile Function (IIEF) questionnaire, completed at baseline and after 12 weeks of treatment. At end point, mean scores for all IIEF domains of sexual function (erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction) were significantly (P<0.0001) higher in the sildenafil group (n=109) than in the placebo group (n=105). These findings confirm the significant increases in frequency of penetration and frequency of maintained erections reported previously. Sildenafil treatment was well tolerated. The most common adverse events were headache and flushing. In conclusion, sildenafil is a well-tolerated and effective treatment for ED of broad-spectrum etiology in Latin American men.