Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic and Pharmacodynamic Properties of a New Thromboxane Receptor Antagonist (Z‐335) after Single and Multiple Oral Administrations to Healthy Volunteers

The pharmacokinetics and pharmacodynamics of a new oral thromboxane (TX) A2 receptor antagonist, Z‐335, were studied in healthy male volunteers following single doses (0.5–40 mg, PO) in a dose‐escalating manner and multiple doses (40 mg, PO, once daily for 7 consecutive days) with a single‐blind, placebo‐controlled design. Serial blood and urine samples were analyzed for Z‐335 and its metabolites to obtain key pharmacokinetic parameters. In the single‐dose (10, 20, and 40 mg) study, the maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) increased in proportion to the dose when administered after fasting, while the mean elimination half‐life (t1/2β) was essentially unchanged (7.79‐7.93 h). Recovery of the unchanged and taurine‐conjugated drugs in the urine within 24 hours was 6.5% to 8.4% and 11.9% to 14.2%, respectively. These parameters essentially remained unchanged when the effect of meal intake was evaluated at the dose of 20 mg with a crossover design. Ex vivo platelet aggregation in the plasma by a TXA2 analogue, U46619, was completely inhibited within 2 hours after all doses, and complete inhibition was maintained for 12 to 14 hours, depending on the dose. The aggregation induced by collagen was also inhibited to a lesser extent, whereas that by adenosine diphosphate was hardly influenced. In themultiple‐dose study, Cmax and AUC0–24 were increased by 34% after the last dose compared with the first dose. Z‐335 afforded extensive inhibition of platelet aggregation by U46619 throughout the administration period, which returned, however, almost to the control level 48 hours after the last dose. The agent was well tolerated without any abnormalities in subjective and objective symptoms, blood biochemistry, hematology, and urinalysis definitely attributable to the agent, except for the changes expected from its TXA2 receptor‐antagonizing actions. Z‐335 was concluded to be safe and to provide long‐lasting blockade of TXA2 receptors on the basis of a once‐daily regimen, promoting further clinical evaluation.
Nonlinear Disturbance Observers: Design and Applications to Euler?Lagrange Systems

The estimation of unknown inputs and/or disturbances has been a topic of constant interest in control engineering for the past several decades; see [1] for a detailed survey on the development of unknown input observers. Disturbance observers (DOBs) are a special class of unknown input observers that were introduced for robust motion-control applications in the early 1980s [2]. Since their introduction in the literature, DOBs have been employed efficaciously in numerous robust control and fault-detection applications, including process control [3], [4] and mechatronics [5]-[9]. Figure 1 depicts a DOB employed in a typical control system. The DOB is used to reconstruct, from the measured output variables and the known control inputs applied to the system, unknown disturbances that are acting on the plant. The output of the DOB, namely, the estimated disturbance, can then be used in feedforward compensation of disturbances or faults.
Transcriptional Activity of Androgen Receptor Is Modulated by Two RNA Splicing Factors, PSF and p54nrb

ABSTRACT Nuclear receptors regulate gene activation or repression through dynamic interactions with coregulators. The interactions between nuclear receptors and RNA splicing factors link gene transcription initiation with pre-mRNA splicing, providing a coordinated control of the products of gene transcription. Here we report that two RNA splicing factors, PTB-associated splicing factor (PSF) and p54nrb, synergistically form protein complexes with the androgen receptor (AR) in a ligand-independent manner and inhibit its transcriptional activity. PSF does not affect AR protein stability, as in the case of the progesterone receptor, but impedes the interaction of AR with the androgen response element. Both splicing factors interact directly with mSin3A and attract mSin3A to the AR complex in a synergistic manner. The suppression of AR transcriptional activity by PSF and p54nrb is reversed by the inhibition of histone deacetylase activity. These data demonstrated that PSF and p54nrb complex with AR and play a key role in modulating AR-mediated gene transcription.
Prognostic Association of Anxiety Post Myocardial Infarction With Mortality and New Cardiac Events: A Meta-Analysis

Objective: To assess the association of anxiety after myocardial infarction (MI) with cardiac prognosis. Methods: A meta-analysis of references derived from MEDLINE, EMBASE, and PSYCINFO (1975–March 2009) was performed without language restrictions. End point was cardiac outcome defined as all-cause mortality, cardiac mortality, and cardiac events. The authors selected prospective studies with at least 6 months follow-up, and anxiety had to be assessed within 3 months after MI with reliable and valid instruments. Results: Twelve papers met selection criteria. These studies described follow-up (on average, 2.6 years) of 5750 patients with MI. Anxious patients were at risk of adverse events (odds ratio (OR) fixed, 1.36; 95% confidence interval (CI), 1.18–1.56; p < . 001). Anxiety was also specifically associated with all-cause mortality (OR fixed, 1.47; 95% CI, 1.02–2.13; p = .04), cardiac mortality (OR fixed, 1.23; 95% CI, 1.03–1.47; p = .02), and new cardiac events (OR fixed, 1.71; 95% CI, 1.31–2.23; p < .001). Conclusions: Post-MI anxiety is associated with a 36% increased risk of adverse cardiac outcomes in bivariate analyses. Because the existing literature is small and contains several limitations, more research is needed to evaluate the association of anxiety and prognosis in patients with MI and to assess the extent to which this association is independent of clinical variables, such as disease severity, and other psychological variables, especially depression. BMI = body mass index; CABG = coronary artery bypass graft; CHD = coronary heart disease; CI = confidence interval; CBAHF = Cognitive Behavioral Assessment Hospital Form; ENRICHD = Enhancing Recovery in Coronary Heart Disease Patients; FEM = fixed effects model; GAD = generalized anxiety disorder; HADS = Hospital Anxiety and Depression Scale; HR = hazard ratio; LVEF = left ventricular ejection fraction; MI = myocardial infarction; MIND-IT = Myocardial Infarction and Depression Intervention Trial; NA = not available; OR = odds ratio; REM = random effects model; STAI = State Trait Anxiety Inventory; STPI = State Trait Personality Inventory; UA = unstable angina.
The child's worries about the mother's breast cancer: sources of distress in school-age children.

PURPOSE/OBJECTIVES To describe children's worries when their mothers are newly diagnosed with early-stage breast cancer. DESIGN Descriptive, qualitative study. SETTING Private family homes. SAMPLE Case intensive interviews with 16 children who ranged in age from 11-18 years at the time that interviews were conducted and who had been 8-12 years of age when their mothers were diagnosed with early-stage breast cancer. METHODS Semistructured interviews with the children were audiorecorded, transcribed, and inductively coded into categories of distinct worries about their mothers' breast cancer. MAIN RESEARCH VARIABLES Children's descriptions of their worries and confusion resulting from their mothers' breast cancer diagnoses. FINDINGS The children voiced nine categories of worry during the interviews: worrying that the mother was going to die; feeling confused; worrying that something bad would happen; worrying about the family and others; worrying when the mother did not look good; worrying that their mothers would change; wondering if the family would have to cut back financially; worrying about talking to others; and wondering if they, the children, would get cancer. CONCLUSIONS Children of mothers with breast cancer experience multiple worries concerning their mothers, their families, and themselves. The data revealed that they attempted to make sense of their mothers' illness for themselves and imagined how it might affect their own lives in the future. IMPLICATIONS FOR NURSING PRACTICE Programs and materials need to be developed that help parents address the multiple worries that children whose mothers have early-stage breast cancer experience.
Phase Retrieval Motivated Nonlinear MIMO Communication With Magnitude Measurements

This paper proposes a multiuser magnitude-only (MO-)MIMO, whose base station acquires quantized magnitudes of the complex baseband signals through envelop detectors and low-resolution ADCs. Consequently, MO-MIMO enjoys much lower circuit power and cost in comparison with the conventional MIMO. Because the phase information is unavailable, all the existing MIMO baseband algorithms cannot be applied into MO-MIMO. Therefore, two types of channel estimators and multiuser detectors are constructed by first categorizing the channel estimation and multiuser detection problems as a quantized phase retrieval (PR) problem, and then solving the latter by developing two methods under the framework of generalized approximate message passing (GAMP). The first method directly applies GAMP to solve the quantized PR problem by exploiting the probability relationships between the quantized magnitude measurements and unknown complex signals. The second method iterates between the missing phase estimation and signal recovery, where the latter calls for GAMP to handle a linear mixing problem with quantized observations. The developed estimators and detectors call for matrix-vector multiplications and nonlinear function calculations as the most complex operations, handle the nonlinear quantization loss specially, and exploit the signal prior probability distributions. Finally, their effectiveness is validated experimentally.
Workplace Injuries in Thoroughbred Racing: An Analysis of Insurance Payments and Injuries amongst Jockeys in Australia from 2002 to 2010

Background: There is no comprehensive study of the costs of horse-related workplace injuries to Australian Thoroughbred racing jockeys. Objectives: To analyse the characteristics of insurance payments and horse-related workplace injuries to Australian jockeys during Thoroughbred racing or training. Methods: Insurance payments to Australian jockeys and apprentice jockeys as a result of claims for injury were reviewed. The cause and nature of injuries, and the breakdown of payments associated with claims were described. Results: The incidence of claims was 2.1/1000 race rides, with an average cost of AUD 9 million/year. Race-day incidents were associated with 39% of claims, but 52% of the total cost. The mean cost of race-day incidents (AUD 33,756) was higher than non-race day incidents (AUD 20,338). Weekly benefits and medical expenses made up the majority of costs of claims. Fractures were the most common injury (29.5%), but head injuries resulting from a fall from a horse had the highest mean cost/claim (AUD 127,127). Conclusions: Costs of workplace injuries to the Australian Thoroughbred racing industry have been greatly underestimated because the focus has historically been on incidents that occur on race-days. These findings add to the evidence base for developing strategies to reduce injuries and their associated costs.
Three essays on growth and economic diversification in resource-rich countries

This thesis looks into the relationship between natural resources and non-resource economic activity in resource-rich countries. This relationship has been investigated through the literature of the “resource curse” which was first noted by Sachs and Warner (1995) who show a significant negative relation between natural resource dependence and income growth. Despite the developing literature in that area, empirical tests suffered from endogeneity. In this thesis, I try to add more resilient identification strategies in order to assess the effect of resource abundance on the macro economy using exogenous variations in 136 countries from 1962-2012. The first essay of this thesis examines the correlation between natural resource rents and economic diversification. The main question I ask in this essay is can resource-rich countries diversify their economies? To address this issue, the essay empirically tests diversification in exports, in employment and in value added and finds a significant negative impact. In the second empirical essay of this thesis, I focus on giant oil and gas discoveries as the main external variation and test the role of institutional quality in diversification when a country becomes resource abundant. Results show that all countries with varied institutional quality go through export concentration after giant oil discoveries. The third empirical essay looks more thoroughly into the manufacturing sector. I estimate the causal effect of two commodity shocks suggested by the Dutch Disease hypothesis on the tradable manufacturing industries: giant oil discoveries as a resource discovery shock, and oil price boom and bust as a commodity price shock. The results suggest a negative impact on the tradable industries growth in manufacturing value added and wages. These results add more credible empirical evidence to the Dutch Disease literature.
Migration of cells from primary transplants of allo‐ and xenografted foetal striatal tissue in the adult rat brain

Primary neural cells derived from human xenografts migrate extensively following transplantation into the adult rat CNS. However, it is unknown whether cells from allografts have the same capability to migrate within the adult rat brain. Moreover, it is unclear whether human‐derived cells migrate to this extent as an inherent property of being in a xenograft environment, or whether it is due to the large size of the developed human brain compared with the adult rat brain. In order to address these issues we have designed an experimental paradigm to investigate the potential for cells derived from grafts of primary rat, mouse and human foetal striatal tissue to migrate following intrastriatal transplantation in an adult rat model of Huntington's disease (HD). Green fluorescent protein (GFP)‐expressing rat and mouse donors and an antibody specific to human nuclear antigen enabled identification of graft‐derived cells within the host brain, and double‐labelling with GFP and neuronal nuclear antigen or immunostaining with human‐specific tau identified graft‐derived neurons. Twelve weeks post‐transplantation, cells had migrated throughout the host in all groups; however, human cells and neurons had migrated significantly more than rat or mouse cells. These results demonstrate that neural cells derived from allografts are capable of migrating in the adult rat CNS and that the extent of migration is most likely determined by the size of the mature donor adult brain. This has important implications for the use of allo‐ and xenogeneic tissue as a source for transplantation in treating diffuse neurodegenerative disorders such as HD.
Melaleuca alternifolia and its application against dental plaque and periodontal diseases: A systematic review

This is a systematic review of clinical and laboratory studies evaluating the effect of Melaleuca alternifolia on periodontopathogens, dental plaque, gingivitis, periodontitis, and inflammatory responses. The PubMed, Cochrane, Web of science, Bireme, Lilacs, Prospero, Open Grey, and Clinical Trials databases were searched to identify potentially eligible studies through October 2016. Of 1,654 potentially eligible studies, 25 were included in the systematic review. Their methodology was evaluated through the Cochrane Handbook for clinical studies and the GRADE system for in vivo/in vitro studies. Although clinical studies must be interpreted with caution due to methodological limitations, laboratory studies have found promising results. In vitro evidences showed that M. alternifolia has bactericidal and bacteriostatic effects against the most prevalent periodontopathogens. Clinical studies found comparable effects to chlorhexidine 0.12% in reducing gingival inflammation, although the antiplaque effect was lower. M. alternifolia also showed antioxidant properties, which are beneficial to the host, allied to the reduction on immune‐inflammatory responses to pathogens. This systematic review suggests that the M. alternifolia has potential anti‐inflammatory and antimicrobial properties, which can be easily applied to the periodontal tissues. However, further clinical trials are needed to elucidate the clinical relevance of its application.
Macroeconomic Determinants of Foreign Direct Investment Inflows and Impulse Response Function

The purpose of the contemporary research was the examination of macroeconomic determinants of foreign direct investment inflows into post-conflict Sierra Leone for the period, 2002-2015, and whether the determinants have a long-run and short-run association with FDI. A complementary exploration was the likely impulse response effect on FDI and GDP of a shock to FDI. The research method was quantitative, applying time series data with 56 observations and 6 variables. Applying the Phillips-Ouliaris cointegration model, the results indicated a statistically significant long-run relationship between FDI inflows and its determinants (Rho = -17.064, Tau = -2.996, p
Basal ganglia volume and proximity to onset in presymptomatic Huntington disease.

OBJECTIVE To determine in presymptomatic individuals who carry the gene mutation for Huntington disease whether proximity to estimated age at onset is associated with volume of basal ganglia, as measured on magnetic resonance imaging scans. DESIGN Survey study involving correlations between basal ganglia volume, measured blind to subject status, and estimation of subjects' age at onset. SETTING Huntington's Disease Presymptomatic Testing Program at The Johns Hopkins University School of Medicine, Baltimore, Md. PATIENTS AND OTHER PARTICIPANTS Subjects included 47 individuals at risk for Huntington disease (ie, off-spring of patients with Huntington disease). Twenty subjects tested positive for the gene mutation but were not symptomatic. Twenty-seven subjects tested negative. MAIN OUTCOME MEASURES Estimated age at onset was calculated for each of 20 gene-positive individuals using an empirically derived formula based on the subject's trinucleotide repeat length and parental age at onset. Each subject's age at the time of the magnetic resonance imaging scan was subtracted from his or her estimated age at onset, yielding estimated years to onset. Volumes of caudate, putamen, and globus pallidus were measured on magnetic resonance imaging scans. RESULTS After controlling for the subject's age at the time of the scan, significant correlations were found between volumes of all basal ganglia structures and years to onset. Gene-positive subjects who were far from onset had smaller basal ganglia volumes than gene-negative subjects for all structures except globus pallidus. Gene-positive subjects who were close to onset had smaller volumes than gene-negative subjects for all basal ganglia structures and had smaller volumes than subjects far from onset for all structures except caudate. CONCLUSIONS The results suggest that atrophy of the basal ganglia occurs gradually, beginning years before symptom onset.
The Effect of Therapeutic Touch on Behavioral Symptoms and Cortisol in Persons with Dementia

Background: Between 75–90% of nursing home (NH) residents with dementia develop behavioral symptoms (BSD) which may be associated with a stress response. Therapeutic touch has been shown to decrease restlessness in NH residents, however the mechanism is unknown. The purpose of this randomized controlled trial (RCT) was to examine the effect of therapeutic touch on BSD and basal cortisol levels among NH residents with dementia. Participants and Methods: Using a double blind experimental interrupted time series ABAB design, 65 participants were assigned to one of three groups. The experimental group received therapeutic touch with contact on the neck and shoulders delivered twice daily for 3 days (administered over 2 separate treatment periods); the placebo group received a mimic treatment identical in appearance, and the control group received routine care. Study outcomes were BSD, measured by the modified Agitated Behavior Rating Scale (mABRS), and salivary cortisol levels, measured by enzyme-linked immunosorbent assay (ELISA). Results: 64 residents, aged 67–93 years (M = 85.5, SD = 5.50), completed the study. Restlessness was significantly reduced in the experimental group compared to the control group (p = 0.03). There was a significant difference in morning cortisol variability among groups across time periods (<0.0001). Findings suggest that therapeutic touch may be effective for management of symptoms like restlessness coupled with stress reduction. At a time when cost containment is a consideration in health care, therapeutic touch is an intervention that is non-invasive, readily learned, and can provide a non-pharmacologic alternative for selected persons with BSD.
Should troponin-T be assessed during exercise stress testing in patients with stable angina pectoris?

OBJECTIVE This study was planned to investigate whether or not troponin-T positivity has occurred during exercise stress testing in patients with stable angina pectoris and if yes, its relationship with the severity of the disease. METHODS One hundred patients with stable angina pectoris who presented with typical chest pain were included in this study. They were subjected to the exercise stress testing according to Bruce protocol. Troponin-T was studied 3 times: immediately before, 6 and 24 hours after the exercise testing. Coronary angiography was performed two hours after the last blood sampling. RESULTS Exercise stress test was found positive in 67 (67%) and negative in 33 (33%) patients. Coronary artery disease was present in 47 (70.1%) of those with positive and in 17 (51.5%) with negative test results. Troponin-T was negative in all the patients before the stress test. Troponin-T was found positive in readings taken 6 and 24 hours after the test in 4 patients (6.2%) with coronary artery disease. Of these patients, 2 had positive and the remaining 2 had negative stress test results. Troponin-T was found negative in readings after the stress test in all the patients without coronary artery disease. The duration of the exercise stress test was found to be significantly shorter in patients with troponin positivity than their counterparts with negativity (277.5 +/- 81 sec vs. 428.8 +/- 195 sec, p = 0.024). Troponin-T positivity after the stress test was found considerably higher in patients with three-vessel disease (p = 0.021). CONCLUSIONS Heavy exercises like stress test may severely lead to myocardial damage. The study of post-stress test tropinin T readings, in patients with stable angina pectoris and with negative stress test result, may be of great help in detecting especially the patients with multiple vessel disease.