Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and Bioequivalence Study of a Generic Amlodipine Tablet Formulation in Healthy Male Volunteers

Abstract Two different tablets containing amlodipine besylate (CAS 111470-99-6) (Vazkor© 10 mg tablet as test preparation and 10 mg tablet of the originator product as reference preparation) were investigated in 18 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence between both treatments after oral single dose administration. The study was performed according to an open-label, randomized, two-period cross-over design with a wash-out phase of 21 days. Blood samples for pharmacokinetic profiling were taken up to 144 h post-dose, and amlodipine plasma concentrations were determined with a validated LC-MS/MS method. Maximum plasma concentrations (Cmax) of 6,183.7 pg/ml (test) and 5,366.7 pg/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC0-∞)of 267,231.0 pg · h/ml (test) and 266,061.7 ng · h/ml (reference) were calculated. The median tmax was 5.6 h (test) and 6.1 h (reference). Plasma elimination half-lives (t1/2) were 46.46 h (test) and 45.34 h (reference). Both primary target parameters AUC0→∞ and Cmax were tested parametrically by analysis of variance (ANOVA); 90% confidence intervals were between 93.20%-107.16% (AUC0→∞ and 103.36%-123.13% (Cmax)- Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%–125%.
Beyond topographic representation: Decoding visuospatial attention from local activity patterns in the human frontal cortex

The ability to detect where a person is attending is fundamental for brain‐computer‐interfaces. We explore how the attentional focus can be decoded from brain signals noninvasively acquired with functional magnetic resonance imaging (fMRI). Several cortical regions have previously been reported to have topographic maps reflecting the focus of visual attention. Interestingly, attentional maps were observed to be gradually less topographic when moving from early visual areas toward extra‐occipital areas. Recent studies suggested that this might indicate a shift from topographically represented local processing to a global processing dominated by laterality. However, it remains unclear, to which extent the topographical representation of a region characterizes its quality to encode visuospatial attention. Here we addressed this problem by applying multivoxel pattern analysis to fMRI signals. In combination with a cortical surface‐based mapping of spatial preference, our analysis revealed a broad cortical network that locally contains information about the locus of visual attention. The informative regions are not restricted to topographic areas, but even in frontal areas, where topographic organization is almost indiscernible, the attentional locus can be decoded from brain activity. Specifically, we find attentional information in the right middle frontal gyrus and the right ventrolateral prefrontal cortex. Furthermore, in these two areas information is sufficient to distinguish attentional loci within the ipsi‐ as well as the contra‐lateral visual hemifields. The laterality dominance decreases when moving from occipital to frontal areas. Our results suggest that information about visuospatial attention is encoded beyond topographically organized regions by local patterns of brain activity. VVC 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 201–210, 2011
Three essays on growth and competitiveness of the chinese economy

El objeto de esta Tesis Doctoral es analizar los determinantes del crecimiento economico y competitividad de la economia China e investigar si diferenciales de renta per capita entre sus diferentes regiones tienden a un proceso de convergencia o divergencia durante las ultimas cuatro decadas. En el primer capitulo se reviso el papel desempenado por las exportaciones y la acumulacion de capital en el proceso de crecimiento de la economia China. En el segundo capitulo se analizo especificamente el efecto de la inversion en equipamiento junto con otros factores de crecimiento como las exportaciones, infraestructuras, actividades de innovacion y capital humano sobre el nivel de actividad. En el tercer capitulo se re-examino el orden de integrabilidad de las tasas de crecimiento del output y la productividad. Ademas, se investigo los potenciales determinantes de las tasas de crecimiento del output y la productividad con el objetivo de distinguir si el proceso de crecimiento de la economia China es mas consistente con un modelo a la Solow o con los modelos de crecimiento endogeno. Finalmente, la tesis concluye examinando a nivel regional si las provincias mas pobres en China tienden a un proceso de convergencia (divergencia) respecto a las mas ricas o si se estan formando clusters regionales en terminos de renta per capita. Ademas se examina la existencia de spillovers regionales.
DC grid control through the pilot voltage droop concept: Mitigating consequences of time delays

The control of the individual converters in a voltage-source-converter high-voltage dc (VSC-HVDC) based multi-terminal dc grid is central for the overall performance of the system. A few different variants of power drooped against dc voltage control have been proposed in the literature for the purpose of distributing the power mismatch, following a disturbance, on several converters. One such variant is the pilot voltage droop control concept which involves communication. As is always the case when communication is involved, there is a risk of latencies and even communication failure. This paper proposes a way to mitigate the consequences of latencies for the pilot voltage droop concept. The approach may also have bearing on other control problems, involving communication, where the aim is to adjust the steady state solution based on remote measurements. The proposed solution is established in a stepwise fashion starting from the basic control principle, and the performance is exemplified by time domain simulations with a four station dc grid using Digsilent's Powerfactory platform.
Functional analysis of the Ca(2+)-regulated hemolysin I operon of Actinobacillus pleuropneumoniae serotype 1

The genetic determinant encoding the synthesis and secretion of hemolysin I (HlyI; gene designation, hlyI) by Actinobacillus pleuropneumoniae serotype 1 4074T was cloned in the lambda vector EMBL4. A 10.2-kb fragment that encoded hemolytic activity in the phage lysate was aligned by Southern blot hybridization to genes hlyC, hlyA, hlyB, and hlyD of the Escherichia coli hemolysin operon, and expression of the A. pleuropneumoniae genes in E. coli revealed that they have the same functions as their E. coli analogs: hlyIC encodes a protein that activates inactive 105-kDa prohemolysin I (encoded by hlyIA) to active hemolysin I, while hlyIB and hlyID are necessary for HlyIA secretion. Northern (RNA) hybridization of A. pleuropneumoniae RNA revealed that the gene cluster is transcribed as two RNA species, a major one of 3.5 kb, corresponding to hlyICA, and a second, minor one of 7.5 kb, corresponding to the whole operon, hlyICABD. The level of hlyI mRNA was substantially higher in A. pleuropneumoniae 4074T cells grown in the presence of Ca2+, supporting the view that the expression of the hlyI determinant is Ca2+ regulated. Parallel RNA hybridization with random gene probes suggested that this Ca2+ regulation is specific for the hlyI determinant.
Bayesian Semiparametric Frailty Selection in Multivariate Event Time Data

Biomedical studies often collect multivariate event time data from multiple clusters (either subjects or groups) within each of which event times for individuals are correlated and the correlation may vary in different classes. In such survival analyses, heterogeneity among clusters for shared and specific classes can be accommodated by incorporating parametric frailty terms into the model. In this article, we propose a Bayesian approach to relax the parametric distribution assumption for shared and specific‐class frailties by using a Dirichlet process prior while also allowing for the uncertainty of heterogeneity for different classes. Multiple cluster‐specific frailty selections rely on variable selection‐type mixture priors by applying mixtures of point masses at zero and inverse gamma distributions to the variance of log frailties. This selection allows frailties with zero variance to effectively drop out of the model. A reparameterization of log‐frailty terms is performed to reduce the potential bias of fixed effects due to variation of the random distribution and dependence among the parameters resulting in easy interpretation and faster Markov chain Monte Carlo convergence. Simulated data examples and an application to a lung cancer clinical trial are used for illustration.
Neuronal Substrates of Sleep and Epilepsy

1. Pioneering steps in studies on sleep and epilepsy 2. Neuronal types and circuits in sleep and epilepsy 3. Neuronal properties, network operations and behavioral signs during sleep states and wakefulness 4. Plastic changes in thalamocortical systems developing from low-frequency sleep oscillations 5. Neuronal mechanisms of seizures.
Microsurgery in the Hypercoagulable Patient: Review of the Literature

Abstract Improved techniques in microvascular surgery over the last several decades have led to the increased use of free tissue transfers as a mode of reconstructing difficult problems with a high success rate. However, undiagnosed thrombophilias have been associated with microsurgery free flap failures. We present a case of successful free tissue transfer in a patient with lupus anticoagulant and review the literature.
Eyelid opening induces expression of a glycocalyx glycoprotein of rat ocular surface epithelium.

PURPOSE We previously characterized a monoclonal antibody against a glycoprotein of rat ocular surface glycocalyx (ROSG). This monoclonal antibody recognizes a carbohydrate epitope on a glycoprotein expressed in apical cells of the differentiated ocular surface epithelium. Our goal was to determine the developmental appearance of the ROSG glycoprotein. METHODS We localized the antigen immunohistochemically and immunocytochemically in newborn (day 1) rats and in rats 2-5, 7, and 11-15 days after birth. RESULTS Before eyelid opening (days 12-14), the ROSG antigen was localized in the palpebral conjunctiva near the lid margin. The binding extended to layers of the subapical flattened cells. However, the antigen was not found in the corneal epithelium while the eyelid remained closed. In contrast, at the first day of eyelid opening (days 12-15), the antigen was present contiguously in several cell layers from the eyelid margin along the entire ocular surface, including the corneal epithelium. Thus, the binding pattern seen upon eyelid opening was similar to that of adult rats. The phenomenon of appearance of the glycoprotein upon eyelid opening was further demonstrated in rats with asynchronous eyelid opening. Artificial, premature eyelid opening at days 8-11 also induced the expression of the antigen along the entire ocular surface epithelium, similar to the binding in naturally opened eyes. CONCLUSION Eyelid opening may induce glycosylation or expression of a glycocalyx component that we hypothesize to be involved in mucin spread.
Mandibular osteotomies in patients with juvenile rheumatoid arthritic disease

Objective: This retrospective study evaluates the results after orthognathic surgery in a group of patients with juvenile rheumatoid arthritis. Methods: The material comprised sixteen patients where genioplasty with or without bilateral sagittal split (BSSO) had been performed during a 10‐year period between 1991 and 2000. The patients were recalled for follow‐up examination and the clinical records and radiographs of the patients were analysed. Results: All patients reported an improved facial esthetics. Sixty‐two% reported altered neurosensory dysfunction in the inferior alveolar nerve, but no patients reported altered feelings to interfere with function. Two patients reported reduction in pain in the TMJ from a score 10 and 7 in the VAS‐scale preoperatively, to 0 after the orthognathic surgery. Eight of the patients reported this to be less uncomfortable compared to other surgical procedures because of their JRA. Ninety‐four% noted a positive social change after the operation. Conclusion: Orthognathic surgical treatment of the JRA patient improves the facial profile. The described procedures are safe and serious complications were not seen in our study.
The Evolutionary Economics of Immunity

How much of its resources should an individual invest in a costly immune system? In this article, we apply an evolutionarily stable strategy analysis to an epidemic model to answer this question. On the one hand, an investment in immune function confers protection to infectious agents by reducing host susceptibility, pathogen virulence, or the length of the infectious period. On the other hand, an immune system is costly since it absorbs resources that otherwise might be invested in increasing the host’s fertility or longevity. In addition, an active immune system may be able to clear pathogens efficiently but at the same time may result in immunopathology. By means of a reproductive value approach, we show how to compare the costs and benefits of an immune system systematically and how to derive the evolutionarily stable level of immune function. We then apply these methods to various plausible scenarios. The analysis reveals that the relationship between the life span of an organism and the optimal level of investment in immune function is less straightforward than one might expect. First, the prevalence of infection is reduced to the lowest possible level only under special circumstances. Second, members of a long‐lived species do not necessarily have to invest more in immune function than those of a short‐lived species. In fact, the opposite may be true. Third, the outcome of evolution can be contingent on the initial conditions. Depending on its initial investment strategy, a population may evolve to a state where very much or almost nothing is invested in a costly immune system.
Measurements of Random Telegraph Signal in CCDs Irradiated with Protons and Neutrons

CCD imagers have been irradiated with 10 to 100 MeV protons, 45 MeV neutrons and measurements focussed on random telegraph signal (RTS) characterization. The objective is to propose a method for RTS detection and to analyse pixels behaviour with temperature, particle species and energy.
Early diagnosis of ulnar nerve palsy

Simple, relatively quick, electrophysiologic tests make it possible to diagnose the early cubital tunnel syndrome. Electrophysiologic investigation demonstrated dysfunction of the ulnar nerve due to a lesion localized to the elbow in (1) 60 percent of 56 patients with a presumptive diagnosis of cubital tunnel syndrome but no confirmatory clinical signs, (2) 25 percent of 48 control subjects, and (3) 91 percent of 34 patients with clear-cut clinical evidence of an ulnar nerve compression at the elbow. The terminal motor latency from above the elbow to the abductor digiti quinti minimi muscle was of the most value in diagnosing early cubital tunnel syndrome. If this latency is greater than 9 msec, the diagnosis of the syndrome should be seriously considered.
Cuidados de saúde primários em Portugal

A evolucao dos cuidados de saude primarios em Portugal nos ultimos trinta anos conheceu varias fases. A partir de 1971 foram criados os primeiros centros de saude — os centros de saude de primeira geracao, associados ao que entao se entendia por saude publica —, incluindo actividades como a vacinacao, vigilância de saude da mulher, da gravida e da crianca, saude escolar e ambiental, entre outras. Em 1983 os primeiros centros de saude foram integrados com os numerosos postos dos ex-Servicos Medico-Sociais («caixas»). Este processo de fusao conduziu a uma maior racionalidade formal, mas nao resultou numa melhoria naquilo que eram as principais virtudes dos componentes integrados — acessibilidade a consultas e a visitas domiciliarias, por um lado, e, por outro, a programacao de actividades com objectivos de saude. Em 1999 foi publicada a legislacao sobre os «centros de saude de terceira geracao». Esta aparece na sequencia de experiencias sobre o terreno — «projectos Alfa» e outras iniciativas semelhantes, baseados numa filosofia de «pratica de grupo» — e do inicio de um regime remuneratorio experimental para a clinica geral. As unidades operativas dos novos centros de saude pressupoem um processo de mudanca organizacional que nao pode ser implementada pela via normativa classica tipo top down. Embora necessite de um enquadramento «de cima», a sua realizacao dependera essencialmente da capacidade de despoletar uma dinâmica de mudanca em cada centro de saude e de proporcionar acompanhamento e apoio tecnico a esses processos de mudanca locais.
Induced systemic listeriosis in Alectoris chukar chicks: clinical, histopathological and microbiological findings

Abstract 1. Systemic listeriosis was induced in 14-d-old Chukar partridge chicks, Alectoris chukar, by intravenous injection of a suspension containing 106 cfu/ml of viable Listeria monocytogenes organisms to study the course of infection. 2. Septicaemic and encephalitic forms of listeriosis were observed in all birds. Infection resulted in a fever response 8-h post-inoculation. Disease rapidly developed over a 24-h period with decreased activity, lethargy, ruffled feathers, huddling, listlessness, inability to stand, wing droop, decreased feed and water consumption, growth depression, neural disturbances and finally death. Gross and histopathological changes were observed in the myocardium, proventriculus, gizzard, intestine, pancreas, kidney, liver, spleen, lung, meninges and joints. 3. The diversity of these clinical signs and lesions suggests a high susceptibility of Chukar partridge chicks to systemic listeriosis.
Comparison of On-Treatment Platelet Reactivity Between Triple Antiplatelet Therapy With Cilostazol and Standard Dual Antiplatelet Therapy in Patients Undergoing Coronary Interventions

Background: The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity. Methods: Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 µmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error <. 05 was considered as a level of significance. Results: Compared to dual antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 µmol/L (MD: −14.4, CI: −21.6 to −7.2, P < .001) and 20 µmol/L (MD: −14.9, CI: −22.9 to −6.8, P < .001), significantly lower PRUs (MD: −45, CI: −59.4 to −30.6, P < .001) and PRI (MD: −26, CI: −36.8 to −15.2, P < .001), and significantly higher P2Y12% inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025). Conclusion: Addition of cilostazol to conventional dual antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy.
Retained Foreign Bodies after Emergent Trauma Surgery: Incidence after 2526 Cavitary Explorations

Trauma patients are thought to be at high risk for iatrogenic retained foreign bodies (RFBs). The objective of this study was to evaluate this incidence. All cases of RFB after cavitary trauma surgery were identified by review of Morbidity and Mortality reports at a Level 1 trauma center from January 1998 to December 2005 and confirmed by the Octagon Risk Management System. Over 8 years, 10,053 trauma operations were performed (2075 laparotomies, 377 thoracotomies, and 74 sternotomies). Three cases (0.1%) of RFB (all sponges) occurred during one single-stage and two damage control laparotomies. The counts were correct before definitive closure in two of three cases. No postoperative x-rays were obtained in any of the cases. RFB diagnosis occurred between days 3 and 9, one on a routine chest x-ray and the other two on abdominal computed tomography scans during a septic workup. Four-month to 8-year follow up documented one pleural effusion and one abscess resulting from the RFB. Iatrogenic RFBs after emergent cavitary trauma surgery occur at a rate of 0.12 per cent and are associated with significant morbidity. In addition to standard preventive strategies, in emergent cases with risk factors such as requiring damage control, before final cavity closure, even with a correct sponge count, radiographic evaluation is warranted.
An analysis of five negative sprite‐parent discharges and their associated thunderstorm charge structures

In this study we analyze the discharge morphologies of five confirmed negative sprite‐parent discharges and the associated charge structures of the thunderstorms that produced them. The negative sprite‐parent lightning took place in two thunderstorms that were associated with a tropical disturbance in east central and south Florida. The first thunderstorm, which moved onshore in east central Florida, produced four of the five negative sprite‐parent discharges within a period of 17 min, as it made landfall from the Atlantic Ocean. These negative sprite‐parents were composed of bolt‐from‐the‐blue (BFB), hybrid intracloud‐negative cloud‐to‐ground (IC‐NCG), and multicell IC‐NCGs discharges. The second thunderstorm, which occurred inland over south Florida, produced a negative sprite‐parent that was a probable hybrid IC‐NCG discharge and two negative gigantic jets (GJs). Weakened upper positive charge with very large midlevel negative charge was inferred for both convective cells that initiated the negative‐sprite‐parent discharges. Our study suggests tall, intense convective systems with high wind shear at the middle to upper regions of the cloud accompanied by low cloud‐to‐ground (CG) flash rates promote these charge structures. The excess amount of midlevel negative charge results in these CG discharges transferring much more charge to ground than typical negative CG discharges. We find that BFB discharges prefer an asymmetrical charge structure that brings the negative leader exiting the upper positive charge region closer to the lateral positive screening charge layer. This may be the main factor in determining whether a negative leader exiting the upper positive region of the thundercloud forms a BFB or GJ.