Miracle-dz/UniFAR-FTUs huggingface dataset:
A Breath of Fresh Air? Firm Type, Scale, Scope, and Selection Effects in Drug Development

This paper compares the innovation performance of established pharmaceutical firms and biotech companies, controlling for differences in the scale and scope of research. We develop a structural model to analyze more than 3,000 drug research and development projects advanced to preclinical and clinical trials in the United States between 1980 and 1994. Key to our approach is careful attention to the issue of selection. Firms choose which compounds to advance into clinical trials. This choice depends not only on the technical promise of the compound, but also on commercial considerations such as the expected profitability of the market or concerns about product cannibalization. After controlling for selection, we find that (a) even after controlling for scale and scope in research, established pharmaceutical firms are more innovative than newly entered biotech firms; (b) older biotech firms display selection behaviors and innovation performances similar to established pharmaceutical firms; and (c) compounds licensed during preclinical trials are as likely to succeed as internal compounds of the licensor, which is inconsistent with the “lemons” hypothesis in technology markets.
Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm

Diagnosis and management of coronary artery disease represents major challenges to our health care system, affecting millions of patients each year. Until recently, the diagnosis of coronary artery disease was possible only through cardiac catheterization and invasive coronary angiography. To avoid the risks of an invasive procedure, stress testing is often employed for an initial assessment of patients with suspected coronary artery disease, serving as a gatekeeper for cardiac catheterization. With the emergence of non-invasive coronary angiography, the question arises if such a strategy is still sensible, particularly, in view of only a modest agreement between stress testing results and the presence of coronary artery disease established by cardiac catheterization. Much data in support of the diagnostic accuracy and prognostic value of non-invasive coronary angiography by computed tomography have emerged within the last few years. These data challenge the role of stress testing as the initial imaging modality in patients with suspected coronary artery disease. This article reviews the clinical utility, limitations, as well as the hazards of stress testing compared with non-invasive coronary artery imaging by computed tomography. Finally, the implications of this review are discussed in relation to clinical practice.
Characterization and Comparison of Mycobacterial Antigens by Two-Dimensional Immunoelectrophoresis

Two-dimensional immunoelectrophoresis (2D-IEP), in which a complex of antigens is subjected to electrophoresis first through an agarose matrix in one direction and secondly through an antiserum-agarose matrix at right angles to the first direction, was evaluated as a tool for analysis of mycobacterial antigens. Cell extracts from four species of mycobacteria, Mycobacterium tuberculosis (four strains), M. bovis strain BCG, M. scrofulaceum, and M. phlei, were assayed by 2D-IEP with four anti-mycobacterial antisera. Besides displaying the precipitin curves in a more easily interpreted format than did conventional immunoelectrophoresis (IEP), 2D-IEP offered greater sensitivity in terms of numbers of precipitin curves when like reactions were compared with IEP patterns. As many as 60 immunoprecipitates were observed on 2D-IEP slides compared to 18 on comparable IEP plates. Technical reproducibility of patterns from run to run was excellent. Other parameters, such as the influence of using different batches of antigen on the pattern, are discussed. Each of the cell extract antigens gave a unique pattern of precipitin peaks which could be easily differentiated from the patterns given by the other mycobacterial cell extracts when reacted with any of the antisera in 2D-IEP. Since both the species and strains of mycobacteria could be easily and reproducibly differentiated solely on the basis of two-dimensional immunoelectrophoretic patterns obtained with any of the antisera employed in this study, it may be possible, by using IEP, to differentiate and identify all species and strains of mycobacteria with one standard, highly sensitive antiserum, rather than a battery of antisera.
Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson's Disease Patients

The impact of Parkinson's disease (PD) on psychological status and quality of life (QoL) may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3 (SD = 10.4) yr were recruited in this study. PD patients with the onset age of ≤50 yr were defined as “early-onset” (EOPD) group (n = 45), while the ones with >50 yr at the time of diagnosis were categorized as the “typical-onset” (TOPD) patients (n = 95). Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale), FSS (fatigue severity scale), MNA (mininutritional assessment), and the UPDRS. Depression score was significantly higher in EOPD group (6.3 (SD = 4.5) versus 4.5 (SD = 4.2), P = 0.02). Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 (SD = 21.6) versus 24.4 (SD = 22.7), P = 0.05). Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients.
Extracorporeal Gas Exchange and Spontaneous Breathing for the Treatment of Acute Respiratory Distress Syndrome: An Alternative to Mechanical Ventilation?*

Objectives:Venovenous extracorporeal gas exchange is increasingly used in awake, spontaneously breathing patients as a bridge to lung transplantation. Limited data are available on a similar use of extracorporeal gas exchange in patients with acute respiratory distress syndrome. The aim of this study was to investigate the use of extracorporeal gas exchange in awake, spontaneously breathing sheep with healthy lungs and with acute respiratory distress syndrome and describe the interactions between the native lung (healthy and diseased) and the artificial lung (extracorporeal gas exchange) in this setting. Design:Laboratory investigation. Setting:Animal ICU of a governmental laboratory. Subjects:Eleven awake, spontaneously breathing sheep on extracorporeal gas exchange. Interventions:Sheep were studied before (healthy lungs) and after the induction of acute respiratory distress syndrome via IV injection of oleic acid. Six gas flow settings (1–10 L/min), resulting in different amounts of extracorporeal CO2 removal (20–100% of total CO2 production), were tested in each animal before and after the injury. Measurements and Main Results:Respiratory variables and gas exchange were measured for every gas flow setting. Both healthy and injured sheep reduced minute ventilation according to the amount of extracorporeal CO2 removal, up to complete apnea. However, compared with healthy sheep, sheep with acute respiratory distress syndrome presented significantly increased esophageal pressure variations (25 ± 9 vs 6 ± 3 cm H2O; p < 0.001), which could be reduced only with very high amounts of CO2 removal (> 80% of total CO2 production). Conclusions:Spontaneous ventilation of both healthy sheep and sheep with acute respiratory distress syndrome can be controlled via extracorporeal gas exchange. If this holds true in humans, extracorporeal gas exchange could be used in awake, spontaneously breathing patients with acute respiratory distress syndrome to support gas exchange. A deeper understanding of the pathophysiology of spontaneous breathing during acute respiratory distress syndrome is however warranted in order to be able to propose extracorporeal gas exchange as a safe and valuable alternative to mechanical ventilation for the treatment of patients with acute respiratory distress syndrome.
Voltage‐dependent membrane potential oscillations of rat striatal fast‐spiking interneurons

We used whole‐cell recordings to investigate subthreshold membrane potential oscillations and their relationship with intermittent firing in striatal fast‐spiking interneurons. During current injections (100–500 pA, 1 s), these cells displayed a highly variable pattern of spike bursts (comprising 1–30 action potentials) interspersed with membrane potential oscillations. The oscillation threshold was −42 ± 10 mV, and coincided with that for action potentials. The oscillation frequency was voltage dependent and ranged between 20 and 100 Hz. Oscillations were unaffected by the calcium channel blockers cadmium and nickel and by blockers of ionotropic glutamate and GABA receptors. Conversely, the sodium channel blocker tetrodotoxin fully abolished the oscillations and the spike bursts. The first spike of a burst appeared to be triggered by an oscillation, since the timing and rate of rise of the membrane potential in the subthreshold voltage region was similar for the two events. Conversely, the second spike (and the subsequent ones) displayed much faster depolarisations in the subthreshold voltage range, indicating that they were generated by a different mechanism. Consistent with these notions, a small pulse of intracellular current delivered during the oscillation was effective in triggering a burst of action potentials that largely outlasted the pulse. We conclude that fast‐spiking interneuron oscillations are generated by an intrinsic membrane mechanism that does not require fast synaptic transmission, and which depends on sodium conductance but not calcium conductance, and that such oscillations are responsible for triggering the intermittent spike bursts that are typical of these neurons.
The Pentapeptide RM-131 Promotes Food Intake and Adiposity in Wildtype Mice but Not in Mice Lacking the Ghrelin Receptor

The gastrointestinal peptide hormone ghrelin is the endogenous ligand of the growth hormone secretagogue receptor (a.k.a. ghrelin receptor, GHR). Currently, ghrelin is the only circulating peripheral hormone with the ability to promote a positive energy balance by stimulating food intake while decreasing energy expenditure and body fat utilization, as defined in rodents. Based on these and additional, beneficial effects on metabolism, the endogenous ghrelin system is considered an attractive target to treat diverse pathological conditions including those associated with eating/wasting disorders and cachexia. As the pharmacological potential of ghrelin is hampered by its relatively short half-life, ghrelin analogs with enhanced pharmacokinetics offer the potential to sustainably improve metabolism. One of these ghrelin analogs is the pentapeptide RM-131, which promotes food intake and adiposity with higher potency as compared to native ghrelin in rodents. Whereas, the effect of RM-131 on energy metabolism is solidly confirmed in rodents, it remains elusive whether RM-131 exerts its effect solely via the ghrelin receptor. Accordingly, we assessed the receptor specificity of RM-131 to promote food intake and adiposity in mice lacking the GHR. Our data show that in wildtype mice RM-131 potently promotes weight gain and adiposity through stimulation of food intake. However, RM-131 fails to affect food intake and body weight in mice lacking the GHR, underlining that the anabolic effects of RM-131 are mediated via the ghrelin receptor in mice.
Tackling magnetoencephalography with particle swarm optimization

This paper investigates the performance of particle swarm optimization (PSO) and unified particle swarm optimization (UPSO) in magnetoencephalography (MEG) problems. For this purpose, two interesting tasks are considered. The first is the source localisation problem, also called the 'inverse MEG problem', where an unknown excitation source has to be identified, based on a set of sensor measurements that can be contaminated by noise. We refer to the second task as 'forward task for inverse use'. It consists of the detection of the proper coefficients for approximating the magnetic potential through a spherical expansion, as accurately as possible. Also, the study of their behaviour under variations of the number of available measurements is considered. The obtained results are statistically analysed, providing useful insight regarding the applicability of the employed algorithms on such problems. Also, significant indications regarding the behaviour of several intrinsic dependencies of the problem are derived.
Chronic Elevation of Tumor Necrosis Factor-&agr; Mediates the Impairment of Leptomeningeal Arteriogenesis in db/db Mice

Background and Purpose— Leptomeningeal collateral growth is a key factor that defines the severity of ischemic stroke. Patients with stroke generally have vascular risk factors, such as diabetes mellitus; however, consensus is lacking on how diabetes mellitus affects leptomeningeal arteriogenesis. We investigate the influence of diabetes mellitus on the leptomeningeal arteriogenesis. Methods— We measured the vessel diameter of the leptomeningeal anastomoses 14 days after the common carotid artery occlusion in db/db, db/+, and streptozotocin-induced hyperglycemic mice. In another set of these mice, we measured the infarct volume attributed to subsequent middle cerebral artery occlusion 14 days after the common carotid artery occlusion. Mac-2–positive cells on the dorsal brain surface and the mRNA expression of several macrophage-related factors in the cerebral cortex were examined. Finally, we tested whether the leptomeningeal arteriogenesis could be restored by pharmaceutical intervention in the db/db mice. Results— Cerebral hypoperfusion led to significant ipsilateral leptomeningeal collateral growth in db/+ mice and streptozotocin-induced hyperglycemic mice. The collateral growth contributed to reduced infarct volume. In contrast, leptomeningeal arteriogenesis was impaired in the db/db mice. The number of Mac-2–positive cells was increased and tumor necrosis factor-&agr; mRNA expression was induced after common carotid artery occlusion in the db/+ mice. However, these responses were not observed in the db/db mice. Administration of the tumor necrosis factor-&agr; inhibitor etanercept before common carotid artery occlusion restored the hypoperfusion-induced leptomeningeal collateral growth in db/db mice. Conclusions— These results indicate that leptomeningeal arteriogenesis is impaired in db/db mice and that suppression of the tumor necrosis factor-&agr; response to hypoperfusion is the major contributing factor.
Thymocytes, pre-B cells, and organ changes in a mouse model of chronic ethanol ingestion--absence of subset-specific glucocorticoid-induced immune cell loss.

BACKGROUND The well-known immune deficiency of the chronic alcoholic dictates the need for a long-term rodent ethanol administration model to evaluate the baseline immunologic effects of chronic ethanol abuse, and investigate the genetic determinants of those effects. Much published work with rodents has shown clearly that acute ethanol administration and short-term ethanol-containing liquid diets both cause elevated corticosterone and can cause significant thymocyte, pre-B cell and peripheral lymphocyte losses. Such losses may mask more subtle alterations in immune homeostasis, and in any case are generally short-lived compared with the span of chronic ethanol abuse. Thus, it is important to have a model in which long-term immune alterations can be studied free of corticosteroid-induced cell losses. METHODS We have utilized chronic 20% (w/v) ethanol in water administration to several mouse strains for prolonged periods of time and evaluated serum corticosterone, immunologic stress parameters, and other organ changes by standard methods. RESULTS We now confirm earlier reports that chronic ethanol in water administration to mice does not produce net elevations of corticosterone, although diurnal variation is altered. Importantly, there is neither selective loss of immune cell populations known to be corticosteroid sensitive, CD4+CD8+ thymocytes and pre-B cells, nor are changes observed in the histologic appearance of the thymus. Nonetheless, there are significant chronic ethanol effects in other tissues, including reduced heart weight, mild hepatic steatosis, alterations of gut flora, increased serum peptidoglycan, and as published elsewhere, immune system abnormalities. CONCLUSIONS This model of ethanol administration is convenient, sustainable for up to 1 year, demonstrably feasible in several mouse strains, permits good weight gains in most strains, and results in significant changes in a number of organs. The administration method also will permit modeling of long-term steady abuse punctuated by major binges, and is suitable for supplementation studies using water soluble additives. Overall, the method is useful for a wide range of studies requiring a chronic low-stress method of ethanol administration.
A Genome-Wide Analysis of Liberal and Conservative Political Attitudes

The assumption that the transmission of social behaviors and political preferences is purely cultural has been challenged repeatedly over the last 40 years by the combined evidence of large studies of adult twins and their relatives, adoption studies, and twins reared apart. Variance components and path modeling analyses using data from extended families quantified the overall genetic influence on political attitudes, but few studies have attempted to localize the parts of the genome which accounted for the heritability estimates found for political preferences. Here, we present the first genome-wide analysis of Conservative-Liberal attitudes from a sample of 13,000 respondents whose DNA was collected in conjunction with a 50-item sociopolitical attitude questionnaire. Several significant linkage peaks were identified and potential candidate genes discussed.
Trace: Tennessee Research and Creative Exchange Nursing Publications and Other Works Nursing Effects of Individualized Acupuncture on Sleep Quality in Hiv Disease Recommended Citation Effects of Individualized Acupuncture on Sleep Quality in Hiv Disease

Although it may begin at any point, sleep disturbance often appears early in HIV disease and contributes to decreased quality of life during the course of the illness. Relatively few studies have explored the complex nature of poor sleep quality in HIV disease or tested interventions to improve sleep quality. The purpose of this study was threefold: explore the nature of sleep quality in HIV disease, test the relationship between pain and sleep quality, and test the effectiveness of acupuncture delivered in a group setting for improving sleep quality in those who are HIV infected. A pretest, posttest, preexperimental design was used to test the effects of acupuncture on sleep quality. Participating in the study were 21 HIV-infected men and women between the ages of 29 and 50 years who reported sleep disturbance three or more times per week and who scored greater than 5 on the Pittsburgh Sleep Quality Index. The Wrist Actigraph was used to measure sleep activity, and the Current Sleep Quality Index was used to measure sleep quality for 2 nights before and after a 5-week acupuncture intervention (10 treatments). Acupuncture was individualized to address insomnia and other symptoms reported by the participants. Sleep activity and sleep quality significantly improved following 5 weeks of individualized acupuncture delivered in a group setting. Disrupted sleep quality is a frequent symptom of (73%) of 115 HIV-seropositive patients attending an outpatient HIV/AIDS clinic at an urban teaching hospital were classified as having a sleep disorder as measured by the Pittsburgh Sleep Quality Index (PSQI). Sleep quality is dynamic and is influenced, positively and negatively, by a multitude of physiological, psychological, emotional, psychosocial, and pharmacological factors. The HIV envelope glycoprotein 120 (gp120) induces the secretion of cytokines, such as interleukin-1 (IL-1), interleukin-6 (Il-6), and tumor necrosis factor-alpha (TNF-α), which enhance or sup-TNF-α activate the hypothalamic-pituitary-adrenal axis and stimulate the secretion of hormones that are important in initiating, maintaining, and ending sleep (Chrousos, 1995). Stress may accelerate disease progression by increasing the rate of viral replication, suppressing immunity, and inducing behaviors that are harmful to health (Robinson, Mathews, & Witek-Janusek, 2000). Symptoms of opportunistic infections that occur as HIV disease progresses often result in sleep disturbance. Pain is one such symptom associated with sleep disturbance, which continues to be a major source of suffering and concern for persons with A number of psychosocial factors have the potential to disrupt sleep by the …
Involvement matters: the proper involvement of users and behavioural theories in the design of a medical teleconferencing application

WoundLog is a mobile application that enables district nurses to consult dermatologists, while being in the home situation of the patient. Next to communication tools for teleconferencing and multimedia messaging, it also provides a wound logbook service, and presence, location and availability information of various healthcare professionals. In this paper, we describe the applied user-centred design approach, and a conducted user experiment. The results of the experiment reveal that even district nurses with modest (or no) computing experiences can work adequately with WoundLog. Moreover, they expect that using WoundLog will increase the quality and efficiency of wound care.
Identification of Bilingual Terms from Monolingual Documents for Statistical Machine Translation

This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2289 and by the European Union supported projects EuroSentiment (Grant No. 296277), LIDER (Grant No. 610782) and MateCat (ICT-2011.4.2-287688).
A Procurement Market Model for Reactive Power Services Considering System Security

This paper proposes a two-level framework for the operation of a competitive market for reactive power ancillary services. It is argued that the first-level, i.e., reactive power procurement, be on a seasonal basis while the second-level, i.e., reactive power dispatch, be close to real-time operation. To this effect, a reactive power procurement market model is proposed here taking into consideration system security aspects. This procurement procedure is based on a two-step optimization model. First, the marginal benefits of reactive power supply from each provider with respect to system security are obtained by solving an optimal power flow (OPF) that maximizes system loadability subject to transmission security constraints imposed by voltage limits, thermal limits, and stability limits. Second, the selected set of generators is then determined by solving an OPF-based auction to maximize a societal advantage function comprising generators' offers and their corresponding marginal benefits with respect to system security, considering all transmission system constraints. The proposed procedure yields the selected set of generators and zonal price components, which would form the basis for seasonal contracts between the system operator and the selected reactive power service providers.