Miracle-dz/UniFAR-FTUs huggingface dataset:
Aliskiren in hypertension: evidence for its potential therapeutic value

Introduction: Aliskiren is the first in a new class of antihypertensive drugs that inhibits the conversion of angiotensinogen to angiotensin I by renin, thereby inhibiting production of angiotensin II, the key mediator in the regulation of body fluid volume and blood pressure. Aliskiren is currently in phase III trials as monotherapy and phase II as combination therapy in patients with mild-to-moderate hypertension, and in phase II trials in patients with diabetic nephropathy. Aims: The aim of this review is to evaluate the emerging evidence for use of aliskiren in patients with hypertension and to predict its preliminary place in therapy in clinical outcome terms. All randomized, controlled clinical trials of aliskiren (evidence level 2) were included for analysis of efficacy with the selected outcomes of blood pressure lowering, tolerability, and adherence; all other publications were excluded. Evidence review: The available level 2 evidence, although limited to phase II trials, suggests that aliskiren is effective at lowering blood pressure, an accepted surrogate outcome of morbidity and mortality, in patients with mild-to-moderate uncomplicated essential hypertension. Preliminary evidence suggests aliskiren is as effective as the angiotensin receptor blocker irbesartan, but more studies are needed. The available evidence also suggests that aliskiren is well tolerated and that patients exhibit good adherence to therapy. Aliskiren’s effect on outcomes such as all-cause mortality, reduction in cardiovascular mortality, and reduction in cardiovascular events in patients with mild-to-moderate essential hypertension as well as in special patient populations, remains to be determined. Clinical potential: The evidence available regarding aliskiren’s effect on outcomes, including blood pressure, tolerability, and adherence, supports its use in patients with mild-to-moderate hypertension. Although there is some preliminary evidence from small pilot trials, the use of aliskiren in combination with other antihypertensives, and the use of aliskiren in other patient populations, cannot be recommended without further evidence.
How Costly are Limited Liability Rules?

We analyze the optimal contract, and quantify the cost of limited liability rules, in a standard agency model with ex-ante action choices. Under limited liability, we show that, for typical parametrizations, compensation contracts always specify a "performance target" for the risk-averse agent. Alternatively, in a model of investment financing under moral hazard, external debt and the granting of absolute priority to debtholders are key (though not the unique) ingredients of the optimal financing contract. Removing liability limits makes possible a superior contract that punishes the agent harshly for low-output results. We interpret these harsh penalties in terms of debt bondage (or debtors' prisons), and show that the deadweight losses brought about by the judicial imposition of liability limits are significant. Our results indicate that the costs associated with debt bondage must be substantial to explain the ubiquity of limited liability rules in modern economies.
Validity testing of patient objections to acceptance of tamper-resistant opioid formulations

Background Tamper-resistant formulations (TRFs) of oral opioid drugs are intended to prevent certain types of abuse (eg, intranasal, intravenous). Patients raising objections to receiving a TRF may have valid concerns or may be seeking a formulation that can be more easily misused. Methods US clinicians experienced in pain management met in October 2011 to discuss common patient objections to being switched from a non-TRF opioid to a TRF of the same opioid. Retail pharmacy, health insurance, and scientific data were used to assess the potential validity of these patient objections. Results Clinical experience switching patients from a non-TRF to a TRF opioid was limited to oxycodone controlled release (CR), as it was the only TRF available at that time; knowledge of other TRFs was limited to the scientific literature. Common objections from patients included “costs more,” “not covered by insurance,” “can’t feel it working,” and “causes adverse events. ” Objective retail pharmacy and insurance coverage information for oxycodone CR was accessible and indicated that patient objections were based on cost and coverage varied by insurer. Unpublished trial results (ClinicalTrials.gov) revealed that TRF oxycodone CR has a slower initial release than the non-TRF formulation, which may reduce positive subjective effects. The complaint “I can’t feel it working” may reflect lessened positive subjective effects rather than reduced analgesic efficacy. Most tolerability complaints lacked objective support. Conclusion The general process used to assess the validity of patient objections to TRF oxycodone CR may be applied to other TRFs once they become available. Publication of clinical data on TRFs would help clinicians to appropriately weigh patient concerns.
Choice, Contract, Consent: A Restatement of Liberalism

Choice, Contract, Consent, in restating liberalism, finds its rock-bottom foundations in six first principles that are either self-evident, or readily acceptable to bona fide reason. These simple, relatively undemanding principles dictate the outline of a stable political doctrine. The doctrine is strict, in that it confines the state to mandatory tasks, instead of allowing it discretionary latitude within rules. This is a loose constraint because collective choice can choose its own rules. Political doctrine informs practical politics. In politics, collective choice replace and often overrides individual choice. For this to be legitimate, it does not suffice to respect procedures, such as those demanded by democracy. Collective choice to be morally justified, needs substantive legitimacy too. Choice, Contract, Consent develops the conditions that substantive legitimacy must meet and delineates the restricted class of cases where a liberal government may pre empt the voluntary choices of its citizens.
Sequence Validation of Candidates for Selectively Important Genes in Sunflower

Analyses aimed at identifying genes that have been targeted by past selection provide a powerful means for investigating the molecular basis of adaptive differentiation. In the case of crop plants, such studies have the potential to not only shed light on important evolutionary processes, but also to identify genes of agronomic interest. In this study, we test for evidence of positive selection at the DNA sequence level in a set of candidate genes previously identified in a genome-wide scan for genotypic evidence of selection during the evolution of cultivated sunflower. In the majority of cases, we were able to confirm the effects of selection in shaping diversity at these loci. Notably, the genes that were found to be under selection via our sequence-based analyses were devoid of variation in the cultivated sunflower gene pool. This result confirms a possible strategy for streamlining the search for adaptively-important loci process by pre-screening the derived population to identify the strongest candidates before sequencing them in the ancestral population.
Training and Manpower Development, Employee Productivity and Organizational Performance in Nigeria: an Empirical Investigation

Over time, organizations have been embarking on training and capacity building for their employees so as to enhance productivity and overall performance of the organizations. This is due to the recognition of the important role of training and manpower development in attainment of organizational goals. Consequently, this study investigated the effects of training and manpower development on employees’ productivity and organizational performance in Nigeria, using First Bank of Nigeria Plc as a case study. The study applied structured questionnaires to a sample size of 75 drawn by simple random sampling. The data generated was analyzed using descriptive statistics.The findings of the study show that majority (70%) of the respondents agreed that training and manpower development has enhanced their efficiency and job productivity. Secondly, majority (80%) of the respondents overwhelming agreed that training and manpower development enhanced organizational performance. The study recommends that organizations should conduct training needs assessment to ensure that the right training is given; ensure that their training programmes should be on a continuous basis; and motivate staff who performed exceptionally well during training sessions so that other staff will in turn aspire to excel. Keywords: Capacity Building, Manpower, Organizational Performance, Productivity, Training.
Seasonality of viral respiratory infections in southeast of Brazil: the influence of temperature and air humidity

Viruses are the major cause of lower respiratory tract infections in childhood and the main viruses involved are Human Respiratory Syncytial Virus (HRSV), Human Metapneumovirus (HMPV), Influenzavirus A and B (FLUA and FLUB), Human Parainfluenza Virus 1, 2 and 3 (HPIV1, 2 and 3) and Human Rhinovirus (HRV). The purposes of this study were to detect respiratory viruses in hospitalized children younger than six years and identify the influence of temperature and relative air humidity on the detected viruses. Samples of nasopharyngeal washes were collected from hospitalized children between May/2004 and September/2005. Methods of viral detection were RT-PCR, PCR and HRV amplicons were confirmed by hybridization. Results showed 54% (148/272) of viral positivity. HRSV was detected in 29% (79/272) of the samples; HRV in 23.1% (63/272); HPIV3 in 5.1% (14/272); HMPV in 3.3% (9/272); HPIV1 in 2.9% (8/272); FLUB in 1.4% (4/272), FLUA in 1.1% (3/272), and HPIV2 in 0.3% (1/272). The highest detection rates occurred mainly in the spring 2004 and in the autumn 2005. It was observed that viral respiratory infections tend to increase as the relative air humidity decreases, showing significant association with monthly averages of minimal temperature and minimal relative air humidity. In conclusion, viral respiratory infections vary according to temperature and relative air humidity and viral respiratory infections present major incidences it coldest and driest periods.
Poverty Alleviation and Child Labor

Does child labor decrease as household income rises? This question has important implications for the design of policy on child labor. This paper focuses on a program of unconditional cash transfers in Ecuador. It argues that the effect of a small increase in household income on child labor should be concentrated among children most vulnerable to transitioning from schooling to work. The paper finds support for this hypothesis. Cash transfers have small effects on child time allocation at peak school attendance ages and among children already out of school at baseline, but have large impacts at ages and in groups most likely to leave school and start work. Additional income is associated with a decline in paid work that takes place away from the child's home. Declines in work for pay are associated with increases in school enrollment, especially for girls. Increases in schooling are matched by an increase in education expenditures that appears to absorb most of the cash transfer. However, total household expenditures do not increase with the transfer and appear to fall in households most impacted by the transfer because of the decline in child labor.
Staple Food Prices in Ethiopia

Cereal production and marketing are the means of livelihood for millions of households in Ethiopia. It is the single largest sub-sector within Ethiopia’s agriculture, far exceeding all others in terms of its share in rural employment, agricultural land use, calorie intake, and contribution to national income. Therefore, while the country has experimented with almost all dominant forms of political and economic ideologies,2 keeping the cereal subsector stable has influenced the agricultural policy thinking of all three political regimes over the past half century. The monarchic regime instituted grain market board; the central planning region (1974-91) renamed it the Agricultural Marketing Corporation (AMC) and expanded its scope to practically take over the staple food markets; and while the current government implemented substantial reforms, it continues to maintain the necessary policy instruments to intervene in case of emergencies. There is a widespread recognition that parastatal-centric policies of cereal price stabilization proved expensive and led to inequitable distribution of benefits. However, recent policy actions suggest that, like many other developing countries, Ethiopia is not yet ready to fully rely on markets. This became particularly evident during the food price crisis when the government re-instituted urban food rationing programs, carried out open market sales, and suspended local procurement by the World Food Programme (WFP), country’s food logistic agency (Ethiopian Grain Trading Enterprise), and non-governmental organizations (NGOs). This perhaps reflects the fact that risks of price instability—in term of economic, human, and political costs—is still the predominant consideration in food policy making of the country. This paper discusses the sources of such concerns and how they are reflected in recent policy actions. It provides evidence of the subsector’s significance; characterizes the key cereal markets in terms of production, trade, and price patterns; and summarizes the policy actions following food price crisis. The evidence on the importance of selected cereals is presented in Section 2, which is followed by a discussion of production and trade of those cereals. Section 4 analyzes price patterns, focusing on seasonality and tradability. A summary of public policy actions following the global food crisis is presented in Section 5; and the paper concludes with a summary and implications.
Nonthermal X-Ray Emission: An Alternative to Cluster Cooling Flows?

We report the results of experiments aimed at reducing the major problem with cooling flow models of rich cluster X-ray sources, i.e., the fact that most of the cooled gas or its products have not been found. Here we show that much of the X-ray emission usually attributed to cooling flows can, in fact, be modeled by a power-law component which is indicative of a source(s) other than thermal bremsstrahlung from the intracluster medium. We find that adequate simultaneous fits to ROSAT PSPC and ASCA GIS/SIS spectra of the central regions of 10 clusters are obtained for two-component models that include a thermal plasma component that is attributable to hot intracluster gas and a power-law component that is likely generated by compact sources and/or extended nonthermal emission. For five of the clusters that purportedly have massive cooling flows, the best-fit models have power-law components that contribute ~30% of the total flux (0.14-10.0 keV) within the central 3'. Because cooling flow mass deposition rates are inferred from X-ray fluxes, our finding opens the possibility of significantly reducing cooling rates.
b 1 Integrin Establishes Endothelial Cell Polarity and Arteriolar Lumen Formation via a Par 3-Dependent Mechanism

Ann C. Zovein,1,2,8 Alfonso Luque,1,3,8,9 Kirsten A. Turlo,1,3 Jennifer J. Hofmann,1,3 Kathleen M. Yee,3 Michael S. Becker,3 Reinhard Fassler,4 Ira Mellman,5 Timothy F. Lane,6,7 and M. Luisa Iruela-Arispe1,3,6,* 1Department of Molecular, Cellular, and Developmental Biology 2Division of Neonatology, Department of Pediatrics 3Molecular Biology Institute University of California, Los Angeles, Los Angeles, CA 90095, USA 4Department of Molecular Medicine, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany 5Research Drug Discovery, Genentech, South San Francisco, CA 94080, USA 6Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA 7Department of Obstetrics and Gynecology and Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA 8These authors contributed equally to this work 9Present address: Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain *Correspondence: arispe@mcdb.ucla. edu DOI 10.1016/j.devcel. 2009.12. 006
A Bayesian test to identify variance effects

Identifying genetic variants that regulate quantitative traits, or QTLs, is the primary focus of the field of statistical genetics. Most current methods are limited to identifying mean effects, or associations between genotype and the mean value of a quantitative trait. It is possible, however, that a genetic variant may affect the variance of the quantitative trait in lieu of, or in addition to, affecting the trait mean. Here, we develop a general methodological approach to identifying covariates with variance effects on a quantitative trait using a Bayesian heteroskedastic linear regression model. We show that our Bayesian test for heteroskedasticity (BTH) outperforms classical tests for differences in variation across a large range of simulations drawn from scenarios common to the analysis of quantitative traits. We apply BTH to methylation QTL study data and expression QTL study data to identify variance QTLs. When compared with three tests for heteroskedasticity used in genomics, we illustrate the benefits of using our approach, including avoiding overfitting by incorporating uncertainty and flexibly identifying heteroskedastic effects.
Contribution of Li-Ion Batteries to the Environmental Impact of Electric Vehicles

Battery-powered electric cars (BEVs) play a key role in future mobility scenarios. However, little is known about the environmental impacts of the production, use and disposal of the lithium ion (Li-ion) battery. This makes it difficult to compare the environmental impacts of BEVs with those of internal combustion engine cars (ICEVs). Consequently, a detailed lifecycle inventory of a Li-ion battery and a rough LCA of BEV based mobility were compiled. The study shows that the environmental burdens of mobility are dominated by the operation phase regardless of whether a gasoline-fueled ICEV or a European electricity fueled BEV is used. The share of the total environmental impact of E-mobility caused by the battery (measured in Ecoindicator 99 points) is 15%. The impact caused by the extraction of lithium for the components of the Li-ion battery is less than 2.3% (Ecoindicator 99 points). The major contributor to the environmental burden caused by the battery is the supply of copper and aluminum for the production of the anode and the cathode, plus the required cables or the battery management system. This study provides a sound basis for more detailed environmental assessments of battery based E-mobility.
A Generalization of the Blahut–Arimoto Algorithm to Finite-State Channels

The classical Blahut-Arimoto algorithm (BAA) is a well-known algorithm that optimizes a discrete memoryless source (DMS) at the input of a discrete memoryless channel (DMC) in order to maximize the mutual information between channel input and output. This paper considers the problem of optimizing finite-state machine sources (FSMSs) at the input of finite-state machine channels (FSMCs) in order to maximize the mutual information rate between channel input and output. Our main result is an algorithm that efficiently solves this problem numerically; thus, we call the proposed procedure the generalized BAA. It includes as special cases not only the classical BAA but also an algorithm that solves the problem of finding the capacity-achieving input distribution for finite-state channels with no noise. While we present theorems that characterize the local behavior of the generalized BAA, there are still open questions concerning its global behavior; these open questions are addressed by some conjectures at the end of the paper. Apart from these algorithmic issues, our results lead to insights regarding the local conditions that the information-rate-maximizing FSMSs fulfill; these observations naturally generalize the well-known Kuhn-Tucker conditions that are fulfilled by capacity-achieving DMSs at the input of DMCs.
Marijuana and Youth

This paper contains the first estimates of the price sensitivity of the prevalence of youth marijuana use. Survey data on marijuana use by high school seniors from the Monitoring the Future Project are combined with data on marijuana prices and potency from the Drug Enforcement Administration Office of Intelligence or Intelligence Division. Our estimates of the price elasticity of annual marijuana participation range from 0.06 to 0.47, while those for thirty day participation range from 0.002 to 0.69. These estimates clearly imply that changes in the real, quality adjusted price of marijuana contributed significantly to the trends in youth marijuana use between 1982 and 1998, particularly during the contraction in use from 1982 to 1992. Similarly, changes in youth perceptions of the harms associated with regular marijuana use had a substantial impact on both the contraction in use during the 1982 though 1992 period and the subsequent expansion in use after 1992. These findings underscore the usefulness of considering price in addition to more traditional determinants in any analysis of marijuana consumption decisions made by youths.
What Determines the Implementation of IMF Programs

For many years analysis of IMF conditionality overlooked the extent to which it was implemented. However, more recently increasing attention has been paid to implementation. Theoretical contributions have focused on the importance of special interest groups, but empirical evidence has failed to provide compelling support for the theory. Indeed, empirical studies have reported mixed results that sometimes seem to be conflicting. This paper identifies a range of economic, political and institutional factors that may, in principle, influence implementation. Using various measures of implementation, it then tests an econometric model designed to capture these influences over 1992-2004 exploiting improved sources of data. The results suggest that significant determinants of implementation are trade openness, the existence of veto players and the amount of resources committed by the Fund. The paper offers an interpretation of the results and discusses the implications for policy.
Dielectric breakdown in a 45 nm high-k/metal gate process technology

In this paper, we present extensive breakdown results on our 45nm HK+MG technology. Polarity dependent breakdown and SILC degradation mechanisms have been identified and are attributed gate and substrate injection effects. Processing conditions were optimized to achieve comparable TDDB lifetimes on HK+MG structures at 30% higher E-fields than SiON with a reduction in SILC growth. Extensive long-term stress data collection results and a change in voltage acceleration are reported.