Miracle-dz/UniFAR-FTUs huggingface dataset:
Economic impact of new active substance status on EU payers’ budgets: example of dimethyl fumarate (Tecfidera®) for multiple sclerosis

Background Recently, collaboration between regulators and payers was set up and was mainly focused on evidence generation along product clinical development. However, neither the regulatory path nor the new active substance status (NASs) was considered. Granting NASs will provide the product with 8 years of data protection and 2 years of market exclusivity during which no generic could enter the market. Objective To review the economic impact (for payers) of NASs granted by the European Medicines Agency (EMA) for dimethyl fumarate (DMF), developed by Biogen and approved for multiple sclerosis (MS) as Tecfidera® on 3 February 2014. Method We reviewed the available DMF-containing products and identified their indication and price through relevant databases and official Web sites. The economic impact of Tecfidera® on payers’ budgets was calculated assuming NASs was or was not granted. The forecast was identified in Datamonitor. Results Results identified four products already containing DMF as the main or unique active substance. This would have potentially prevented Tecfidera® from being granted NASs. The EMA Committee for Medicinal Products for Human Use (CHMP) denied Tecfidera® NASs and, following a company appeal, reversed its position opening as polemic. The impact of that decision has been evaluated at €7 to €10 billion over a 10-year period. Conclusion NASs is a critical decision because it does have a major budget impact for payers, and it prevents generic competition. Current European Union (EU) regulations on that topic are unclear and open up too many interpretations thus distorting fair trade and affecting payers’ bills. Greater clarity and more stringent rules are required to prevent mistrust of this EMA decision.
Activation of human bitter taste receptors by polymethoxylated flavonoids

Tangeretin and nobiletin are polymethoxylated flavonoids in citrus peel. Both tangeretin and nobiletin are bitter; however, their bitterness has not been evaluated using human bitter taste receptors (hTAS2Rs). We screened 25 kinds of hTAS2Rs and found that hTAS2R14 and hTAS2R46 received both compounds.
Impact of normative feedback on problem drinkers: a small-area population study.

OBJECTIVE As many as one in four adults in North America experiences some problems due to alcohol consumption. Although most of these problem drinkers do not have concerns that are severe enough to merit formal treatment, such drinking has large economic costs and can place the drinker at risk for long-term negative health and social consequences. The present study evaluated a minimal intervention that used normative feedback about population drinking to motivate changes in alcohol use. METHOD An intervention pamphlet was mailed to over 6,000 households in Toronto, randomized by block from a region containing almost 10,000 households. In the month after the mailing, a general population survey was conducted in the region to assess alcohol use. RESULTS Respondents from households receiving normative feedback (n = 472) reported significantly lower alcohol use than controls (n = 225), but this effect occurred only among respondents who met an objective criterion for problem drinking and who perceived some risk associated with their drinking. CONCLUSIONS Viewed from a public health perspective, normative feedback interventions have the potential for a significant payoff because they can be provided at low cost and to problem drinkers who might ordinarily never access any treatment services.
Top 10 data mining techniques in business applications: a brief survey

Purpose Data mining is widely considered necessary in many business applications for effective decision-making. The importance of business data mining is reflected by the existence of numerous surveys in the literature focusing on the investigation of related works using data mining techniques for solving specific business problems. The purpose of this paper is to answer the following question: What are the widely used data mining techniques in business applications? Design/methodology/approach The aim of this paper is to examine related surveys in the literature and thus to identify the frequently applied data mining techniques. To ensure the recent relevance and quality of the conclusions, the criterion for selecting related studies are that the works be published in reputed journals within the past 10 years. Findings There are 33 different data mining techniques employed in eight different application areas. Most of them are supervised learning techniques and the application area where such techniques are most often seen is bankruptcy prediction, followed by the areas of customer relationship management, fraud detection, intrusion detection and recommender systems. Furthermore, the widely used ten data mining techniques for business applications are the decision tree (including C4.5 decision tree and classification and regression tree), genetic algorithm, k-nearest neighbor, multilayer perceptron neural network, naive Bayes and support vector machine as the supervised learning techniques and association rule, expectation maximization and k-means as the unsupervised learning techniques. Originality/value The originality of this paper is to survey the recent 10 years of related survey and review articles about data mining in business applications to identify the most popular techniques.
The contingent value of venture capitalist reputation

This study explores the signaling and substantive value of high-reputation affiliates to young firms, and the factors that moderate the nature of the value they provide. Specifically, the study examines the extent to which venture capitalist (VC) reputation is related to the first-day valuation and post-IPO operating performance of the firms they take public, and whether the value of a high-reputation VC is contingent on the timing of VC involvement in the portfolio firm, the VC firms’ industry-specific experience and their geographic proximity. The authors develop a time-varying, multi-item composite index of VC reputation and use a sample of VC-backed IPOs between 1990 and 2000 to test their hypotheses. The results suggest that early involvement in an IPO firm’s development significantly enhances the positive relationship between a VC’s reputation and both initial market reactions and post-IPO operating performance. The study also finds that the industry specialization of early-round VCs, regardless of their reputation, is positively related to post-IPO operating performance, and that the relationship is even stronger when the VC has a high reputation and invests in the first round. Finally, while the geographic proximity of VCs to their portfolio firms has no effect on the relationship between their reputation and the firm’s post-IPO operating performance, investors nonetheless discount the value of VC reputation when VCs are more geographically distant from their portfolio firm. However, when endogeneity associated with having greater access to high-potential start-ups is controlled for, geographic proximity significantly decreases the relationship between VC reputation and operating performance, but it no longer affects initial market valuation.
Uplift Capacity of Rock Anchor Groups

The uplift capacity of rock anchor groups was examined by full- scale field tests in different rock formations. The results are analyzed and the different modes of failure are discussed in view of the test results with emphasis on the rock pull-up failure mechanism. Important design parameters are summarized for the convenient use of the engineer in the design of transmission tower foundations anchored in bedrock.
Total learning environment and the implications for rural student nurse retention.

Background: Student cohorts are becoming more diverse and universities need to respond accordingly to meet their needs. Differences within cohorts are a priority area for research, in order to identify how universities can best tailor resources to deal with this diversity. Preventing attrition is a significant factor in planning to meet students needs. In the nursing arena, the attrition rate has widespread implications for the nursing workforce, which is experiencing major shortages especially in rural areas. Method and Results: Themes emerging from a review of the literature include the identification of the first year of university as the most difficult. The literature identifies school leavers and mature aged students as having particular problems, as do students from rural areas, and first generation university students. Mature aged women have more issues associated with the pressures of balancing family, part time work and study and may identify with more than one of these categories. Research supports the claim that students from rural and geographically isolated areas and, particularly, socioeconomically disadvantaged groups, are more at risk of failure and attrition (Bambrick 2002, Lawrence 2002, Howells 2003). Conclusions: A review of literature on this subject has shown that in order to improve the retention of students from diverse groups, universities must ask students what they perceive to be their needs, and then offer appropriate support (Lawrence 2002). Universities need to get to know their own students. What may be suitable for one cohort and one university may differ from what is suitable for others.
Is There an Active Role for Monetary Policy in the Endogenous Money Approach?

In the last two decades or so monetary policy has gained the most prominent role in the economic policy debate. More importantly, academics and policy makers have abandoned the targeting of monetary aggregates, generally considered not to be co-integrated with nominal income, and are now engaged in unison in aggregate demand fine tuning through interest rate management. This is what Laurence Meyer, a member of the Board of Governors of the Federal Reserve System, has defined as the "new consensus" view on macroeconomics (2001). The aggregate demand fine tuning is understood to work through changes in the output gap. The story goes as follows. Changes in real factors such as population, investment in physical and human capital, and technology determine the growth of potential real GDP. Changes in consumption, investment, government expenditure, and net exports determine the growth of aggregate demand. Then, when aggregate demand is greater than potential real GDP, inflation pressures are generated. The reverse holds when aggregate demand grows too slowly. By changing the short-term nominal interest rate, central banks can then bring the growth of aggregate demand in line with the growth of potential output. In the "new consensus" view, inflation is thus a proxy for the state of economic balance. It is an outcome "summary statistic" describing the gap between current and potential output. To put it bluntly, changes in the rate of inflation, and the resulting changes in the interest rate set exogenously by the central bank, are the pri-
Prognostic Factors In Patients with GastroenteropancreaticNeuroendocrine Neoplasms and Hepatic Metastases

Context Hepatic metastases represent the most relevant prognostic factor in gastroenteropancreatic neuroendocrine tumors and are associated with significantly reduced survival. Objective The aim of this single-institution retrospective series was to evaluate overall survival and progression-free survival from the diagnosis of liver metastases. Patients Among 230 consecutive patients diagnosed with gastroenteropancreatic neuroendocrine tumors, between 1995 and 2013, 93 had hepatic metastases: in 48 the primary tumor was pancreatic, in 45 gastrointestinal. Results Median overall survival was 96 months (95% CI, 48-168), 67% of the patients were progressionfree at 5 years. Eleven patients underwent radical surgery, 49 had non-radical resection and medical therapy, 9 had partial resection with peptide receptor radionuclide therapy, 7 had medical treatment with radionuclide therapy; the remaining 17 patients received medical treatment only. Overall, 13 patients (14%) achieved complete remission, 22 (25%) partial remission, 25 (27%) disease stabilization, and 33 (35%) disease progression. The best overall survival (100% at 10 years) was observed in patients with radical resection. Age at diagnosis (p<0.005), low histological grade (p<0.0001), type of treatment (p<0.001), isolated liver involvement (p<0.001) and early chromogranin A decrease after treatment (p<0.0001) were positively associated with OS. At multivariate analysis, type of treatment (p=0.0029), low histological grade (p<0.0001) and early post-treatment chromogranin A decrease (p=0.0078), retained statistical significance, resulting independent predictors of overall survival. No specific factors were associated with progression-free surviva. Conclusions Our data has clearly defined the prognostic factors in a cohort of 93 patients with gastroenteropancreatic neuroendocrine tumors with liver metastasis.
Trouble in Paradise?: The Erosion of System Support in Costa Rica, 1978–1999

Costa Rica has been the real success story of Latin American democracy. For the last half-century, this small country has held free, fair, and competitive elections, experienced regular rotation of rulers and parties, and rarely violated human or civil rights. Consistent voter turnout rates of 80 percent and a firmly entrenched two-party system appeared to be unalterable features of the electoral landscape since the late 1950s. While democracy still seems securely entrenched, the 1998 elections brought a major shift. Abstention increased by 50 percent, and votes for minor parties in the legislature doubled, reaching one-quarter of the electorate. This research note presents evidence that the shift is the result of long-term forces, using cross-sectional survey data collected from 1978 to 1999. Notable declines in the legitimacy of the political system explain the drop in turnout and the rise of minor parties. The study then attempts to explain why this decline may have occurred.
Pilot Randomized Controlled Trial of Auricular Point Acupressure to Manage Symptom Clusters of Pain, Fatigue, and Disturbed Sleep in Breast Cancer Patients

Background: Current management for a symptom cluster of pain, fatigue, and disturbed sleep in breast cancer patients has limited effects. Objective: The purposes of this prospective, randomized controlled pilot study were to (1) assess the feasibility and tolerability of auricular point acupressure (APA) intervention to manage pain, fatigue, and sleep disturbance in breast cancer patients and (2) provide an initial appraisal of effect size as compared with a control intervention. Methods: Thirty-one participants were randomized into either an active APA group (n = 16) or a control APA group (n = 15), which included the sham APA treatment not related to the symptoms. All participants received the APA once a week for 4 weeks. Self-report measures were obtained at baseline, weekly during intervention, at end of intervention, and at a 1-month follow-up. Results: For the 4-week of APA treatment, the retention rate was 88% for the active APA group and 73% for the control APA group. After 4 weeks of APA, participants in the active APA treatment had reported a reduction of 71% in pain, 44% in fatigue, 31% in sleep disturbance, and 61% in interference with daily activities. The control APA group experienced some moderate reduction in these symptoms. Conclusion: Given that this was a pilot study with a small sample size, results must be interpreted with caution. Implications for Practice: Our results suggest that APA may provide an inexpensive and effective complementary approach for the management of symptom clusters for breast cancer patients, and further study is warranted.
Perceptions of surfing tourism operators regarding sustainable tourism development in the Mentawai Islands, Indonesia

ABSTRACT Surfing tourism has the potential to provide significant economic income and employment opportunities. However, the development of surfing tourism in the Mentawai Islands, Indonesia, has raised important questions regarding its impacts and sustainability. Economic leakages, increased pressure on the environment and resources, and adverse effects on local communities have been shown as the major barriers to sustainable development. This article provides insights into how surfing tourism operators perceive the development and impacts of the Mentawai Islands surfing tourism industry. This research project uses an interpretive qualitative approach and follows a case study methodology utilising semi-structured interviews with resort and charter boat surfing tourism operators. The study also investigated possible future directions for creating a more sustainable surfing tourism industry in the Mentawai Islands. Findings from the research showed that charter boat operators and resort operators had differing views as to how surfing tourism had developed: resort operators believed it to be sustainable, while charter boat operators felt it was unsustainable. A key finding of this study was that operators felt that surfing tourism had dramatically altered the traditional Mentawai village of Katiet and was producing adverse socio-cultural impacts on the local community. It is recommended that future research explore the issue of the impacts of surfing tourism development on other remote locations in Indonesia and other surfing tourism destinations around the globe.
Immunohistochemical demonstration of S‐100 protein in salivary gland neoplasms

A peroxidase—antiperoxidase technique for S‐100 protein has been applied to 68 salivary glands. These included 17 pleomorphic adenomas, seven adenoid cystic carcinomas, 23 adenolymphomas and a number of other neoplasms. In addition, five specimens of myoepithelial sialadenitis (‘benign lymphoepithelial lesion’) and five normal parotid glands were included. Consistent results were obtained, myoepithelial cells and cells in myxoid and chondroid areas in pleomorphic adenomas staining intensely. In adenoid cystic carcinoma, on the other hand, there was no staining. The adenolymphomas possessed intensely S‐100 protein‐positive cells in the interfollicular lymphoid areas: these were probably interdigitating reticulum cells. In addition, branching structures, probably corresponding to Langerhans' cells, were observed in the epithelium of adenolymphomas.
Dose estimates for the local inhabitants from 210Po ingestion via dietary sources at a proposed uranium mining site in India

Abstract Purpose: To study the distribution of 210Po activity in food in Bagjata in East Singhbhum, India. Materials and methods: 210Po were analyzed in the food samples of plant origin such as cereals, pulses, fruits, vegetables and food of animal origin such fish, chicken, egg, etc., in and around Bagjata uranium mining area as a part of baseline study after acid digestion. The intake and ingestion dose of the radionuclide was estimated. Results: The general range of 210Po activity in all the dietary components ranged widely from <0.2–36 Bqkg-1fresh. In the food of plant origin, the minimum activity of 210Po was estimated in vegetables while maximum in pulses. In food of animal origin, the observed minimum activity of 210Po was in eggs and the maximum observed was in chicken samples. The intake of 210Po considering all dietary components was found to be 464 Bq.Y-1 while the ingestion dose was calculated to be 557 μSv. Y-1, respectively. The estimated doses are reflecting the natural background dose via the route of ingestion, which is much below the 1 mSv limit set in the International Commission on Radiological Protection (ICRP) recommendations. Conclusion: The study confirms that current levels of 210Po do not pose a significant radiological risk to the local inhabitants.
Tubal flushing for subfertility.

BACKGROUND A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. OBJECTIVES To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent fertility outcomes in couples with infertility. SEARCH STRATEGY We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched 31 January 2007), MEDLINE, EMBASE, Biological Abstract and reference lists of articles. SELECTION CRITERIA All randomised trials comparing tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media or with no treatment in women with subfertility. DATA COLLECTION AND ANALYSIS Four authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials. MAIN RESULTS Twelve trials involving 2079 participants were included. Tubal flushing with oil-soluble media versus no intervention was associated with a significant increase in the odds of live birth (Peto OR 2.98, 95% CI 1.40 to 6.37) and of pregnancy (Peto OR 3.30, 95% CI 2.00 to 5.43). For the comparison of tubal flushing with oil-soluble media versus tubal flushing with water-soluble media, the increase in the odds of live birth for tubal flushing with oil-soluble versus water-soluble media (Peto OR 1.49, 95% CI 1.05 to 2.11) was based on two trials where statistical heterogeneity was present and the higher quality trial showed no significant difference; there was no evidence of a significant difference in the odds of pregnancy (Peto OR 1.21, 95% CI 0.95 to 1.54). The addition of oil-soluble media to flushing with water-soluble media showed no evidence of a significant difference in the odds of pregnancy (Peto OR 1.28, 95% CI 0.92 to 1.79) or live birth (Peto OR 1.06, 95% CI 0.64 to 1.77). There were no serious adverse event reported. AUTHORS' CONCLUSIONS There is evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy and live birth versus no intervention. Future robust randomised trials, comparing oil-soluble versus water-soluble media, water-soluble media versus no intervention and tubal flushing versus established treatments for infertility would be a useful further guide to clinical practice.
Early diagnosis of herpes simplex encephalitis by MRI

The mortality rate of herpes simplex encephalitis (HSE) may be reduced by antiviral therapy, but early administration of the drug and therefore early diagnosis are essential. In our experience with four cases, MRI is the most sensitive noninvasive test in early diagnosis of HSE due to its high sensitivity to inflammatory increased brain water content, and it is superior to CT in localizing the pathognomonic lesions of the limbic system.