Miracle-dz/UniFAR-FTUs huggingface dataset:
Three Michaelis‐Menten Pharmacokinetic Dosing Methods Compared with Physician Dosing of Phenytoin in an Outpatient Neurology Practice

We compared predicted phenytoin serum concentrations using three Michaelis‐Menten pharmacokinetic dosing methods with actual concentrations obtained from physician dosing in an outpatient neurology practice. Method 1 used population estimates for the Michaelis‐Menten constant (Km) and maximum velocity (Vmax), method 2 used one dose and serum concentration pair to determine Vmax, and method 3 used two dose‐concentration pairs to determine both Km and Vmax. In addition, physician doses were compared with pharmacokinetically calculated doses. Records of patients who received at least two phenytoin doses followed by two serum concentration determinations were reviewed. Data on age, gender, weight, physician doses, and resultant serum concentrations were collected. Pearson's correlation coefficient was used to compare physician maintenance doses with pharmacokinetically calculated predicted doses, whereas actual and predicted serum concentration data were used to determine precision and bias associated with each of the three methods. Actual serum concentrations fell into therapeutic range more frequently than predicted values in all but one comparison (method 3). Predicted and actual phenytoin doses were significantly correlated only with method 2. Only one of the three Michaelis‐Menten pharmacokinetic dosing methods evaluated (method 3) was more predictive than physician phenytoin dosing.
What is the role of serology for the study of chronic hepatitis B virus infection in the age of molecular biology?

To assess quantitative serology in chronic hepatitis B virus (HBV) infection, testing by novel immunoassays has been carried out on 202 specimens from untreated patients and in 83 samples from 10 patients with chronic hepatitis B treated with lamivudine. Serum samples were assayed for quantitative HBsAg, in comparison with quantitative HBV‐DNA, and for anti‐HBc IgM and the avidity index (AI) of total anti‐HBc antibodies. The AI was high (mean: 0.93 ± 0.19) in all groups, confirming the consistency of this procedure in chronic HBV infections. A low‐level positivity (2–28 Paul‐Ehrlich units/ml) for IgM anti‐HBc was detectable both in HBeAg‐positive and in HBeAg‐negative untreated chronic hepatitis cases (mean S/CO values by the Abbott Architect assay: 0.51 ± 0.12 and 0.48 ± 0.10, respectively; correlation between assays: r = 0.685), while treated patients (mean: 0.20 ± 0.15) and inactive carriers (mean: 0.17 ± 0.21), were generally negative for IgM. The levels of HBsAg (IU/ml) showed a weak correlation with HBV‐DNA (IU/ml). A difference in HBsAg levels was found between inactive carriers (1,935 ± 2,887 IU/ml) and chronic hepatitis B cases, either treated (5,199 ± 9,259 IU/ml) or untreated (14,596 ± 15,227 IU/ml). Pre‐treatment levels of HBsAg in patients undergoing lamivudine treatment were correlated with a sustained response to therapy over 13–33 months (mean: 27.3) of follow‐up: mean HBsAg values were 1,576 + 1,487 IU/ml in five responders and 6,063 + 5,142 in five nonresponders or breakthrough responders (P < 0.05). The availability of standardized quantitative immunoassays for HBsAg and anti‐HBc IgM may be considered in addition to quantitative HBV‐DNA in the staging and monitoring of chronic HBV infection. J. Med. Virol. 80:974–979, 2008. © 2008 Wiley‐Liss, Inc.
Learning to find your way: a role for the human hippocampal formation

The importance of the hippocampal formation of the brain for allocentric spatial mapping of the environment has been suggested by animal lesion and electrophysiological work. Here we describe a positron emission tomography (PET) study designed to investigate the regional cerebral blood flow changes associated with topographical memory formation in humans, i. e. the formation of representations of largescale environments necessary for way-finding. Topographical learning of an urban environment from viewing of film footage depicting navigation was associated with activation of the right parahippocampal gyrus and hippocampus, with activation also of the left parahippocampal gyrus. In addition, there was activity in the precuneus. In contrast, the encoding of non-navigation episodic memory in a similar real-world context was not associated with activity in the hippocampal formation. Our results shed light on the neural basis of the human representation of large-scale space, pinpointing a particular role for the human hippocampal formation in learning to find one’s way.
The Arabidopsis RNA-Binding Protein AtRGGA Regulates Tolerance to Salt and Drought Stress1[OPEN]

An Arabidopsis RNA-binding protein contributes to drought and salt stress tolerance. Salt and drought stress severely reduce plant growth and crop productivity worldwide. The identification of genes underlying stress response and tolerance is the subject of intense research in plant biology. Through microarray analyses, we previously identified in potato (Solanum tuberosum) StRGGA, coding for an Arginine Glycine Glycine (RGG) box-containing RNA-binding protein, whose expression was specifically induced in potato cell cultures gradually exposed to osmotic stress. Here, we show that the Arabidopsis (Arabidopsis thaliana) ortholog, AtRGGA, is a functional RNA-binding protein required for a proper response to osmotic stress. AtRGGA gene expression was up-regulated in seedlings after long-term exposure to abscisic acid (ABA) and polyethylene glycol, while treatments with NaCl resulted in AtRGGA down-regulation. AtRGGA promoter analysis showed activity in several tissues, including stomata, the organs controlling transpiration. Fusion of AtRGGA with yellow fluorescent protein indicated that AtRGGA is localized in the cytoplasm and the cytoplasmic perinuclear region. In addition, the rgga knockout mutant was hypersensitive to ABA in root growth and survival tests and to salt stress during germination and at the vegetative stage. AtRGGA-overexpressing plants showed higher tolerance to ABA and salt stress on plates and in soil, accumulating lower levels of proline when exposed to drought stress. Finally, a global analysis of gene expression revealed extensive alterations in the transcriptome under salt stress, including several genes such as ASCORBATE PEROXIDASE2, GLUTATHIONE S-TRANSFERASE TAU9, and several SMALL AUXIN UPREGULATED RNA-like genes showing opposite expression behavior in transgenic and knockout plants. Taken together, our results reveal an important role of AtRGGA in the mechanisms of plant response and adaptation to stress.
MOLECULAR DISK PROPERTIES IN EARLY-TYPE GALAXIES

We study the simulated CO emission from elliptical galaxies formed in the mergers of gas-rich disk galaxies. The cold gas not consumed in the merger-driven starburst quickly resettles into a disk-like configuration. By analyzing a variety of arbitrary merger orbits that produce a range of fast- to slow-rotating remnants, we find that molecular disk formation is a fairly common consequence of gas-rich galaxy mergers. Hence, if a molecular disk is observed in an early-type merger remnant, it is likely the result of a “wet merger” rather than a “dry merger. ” We compare the physical properties from our simulated disks (e.g., size and mass) and find reasonably good agreement with recent observations. Finally, we discuss the detectability of these disks as an aid to future observations.
The Diagnosis is Made Only with Suspicion: Miller Fisher Syndrome

Miller Fisher syndrome (MFS) is an uncommon variant of Guillain-Barré syndrome (GBS) characterised by external ophthalmoplegia, ataxia, and areflexia. This syndrome is observed in about 5% of all GBS cases. Miller-Fisher syndrome can be distinguished from GBS by a few clinical features. As the laboratory findings are not specific for MFS, the diagnosis is made only with suspicion of the disease. The aim of this report was to remind the MFS to emergency physicians and to emphasize the differential characteristics and treatment of this neurological emergency. We reported the clinical features of two patients who were diagnosed to have MFS in the emergency department. Emergency physicians should not underestimate the flu like illness together with the typically clinical triad of MFS in the possibility of variant MFS. The first dose IVIG therapy in the ED may be an important factor for early recovery of the patients who have clinically severe findings. (Hong Kong j.emerg.med. 2011;18:428-431)
Understanding pantograph arcing in electrified railways - influence of various parameters

The most common and yet unavoidable EMC problems with electrified railways are due to pantograph arcing. This distorts the waveform of the supply voltage and current, can generates transients during the zero crossings of the current and can cause interference with the traction power and signalling system. Pantograph arcing is a complex phenomenon and depends on speed of the train, current, presence of inductance etc. In a sliding contact like pantograph and contact wire, the arc root moves across both electrodes because of the relative motion between them. In this paper, we will present an experimental analyses of the arc root movement and influence of different parameters on it using a laboratory setup.
Zero-Ripple Input-Current High-Step-Up Boost–SEPIC DC–DC Converter With Reduced Switch-Voltage Stress

This paper proposes a zero-ripple input-current high-step-up boost–single ended primary inductor converter (SEPIC) dc–dc converter with reduced switch-voltage stress to overcome some drawbacks of the conventional cascaded boost–SEPIC dc–dc converter. In the proposed converter, the input current ripple is significantly removed by the auxiliary circuit at the boost stage and the voltage gain is more increased by using turn ratio of a coupled inductor at the SEPIC stage. Additional, the switch-voltage stress is reduced due to the clamping circuit, and the reverse-recovery problem of the output diode is alleviated by the leakage inductor. Hence, the low-voltage-rating MOSFET, which has low $R_{{{\rm ds(on)}}}$, can be utilized as a main switch device. Therefore, the total power efficiency is improved. The theoretical analysis of the proposed converter is verified on an output 200-V to 200-W prototype.
Development and validation of a simple assay for the determination of cholinesterase activity in whole blood of laboratory animals

Current methods for measuring acetylcholinesterase (AChE) activities in whole blood use butyrylcholinesterase (BChE)‐selective inhibitors. However, the poor selectivity of these inhibitors results in the inhibition of AChE activity to some degree, leading to errors in reported values. The goal of this study was to develop and validate a simple assay for measuring AChE and BChE activities in whole blood from humans as well as experimental animals. Blood was fractionated into plasma and erythrocytes, and cholinesterase activities were titrated against ethopropazine and (−)‐huperzine A to determine the lowest concentration of ethopropazine that inhibited BChE completely without affecting AChE activity and the lowest concentration of (−)‐huperzine A that inhibited AChE completely without interfering with BChE activity. Results indicate that 20 µm ethopropazine can be successfully used for the accurate measurement of AChE activity in blood from humans as well as animals. Use of (−)‐huperzine A is not required for measuring BChE activity in normal or ‘exposed’ blood samples. The method was validated for blood from several animal species, including mice, rats, guinea pigs, dogs, minipigs, and African green, cynomolgus and rhesus monkeys. This method is superior to all reported methods, does not require the separation of erythrocyte and plasma fractions, and is suitable for measuring cholinesterase activities in fresh or frozen blood from animals that were exposed to nerve agents or those that were administered high doses of BChE. The method is simple, direct, reproducible, and reliable and can easily be adapted for high‐throughput screening of blood samples. Published 2012. This article is a US Government work and is in the public domain in the USA.
Decreased plasma concentrations of brain-derived neurotrophic factor (BDNF) in patients with functional hypothalamic amenorrhea

Abstract Introduction: Functional hypothalamic amenorrhea (FHA) is a non organic, secondary amenorrhea related to gonadotropin-releasing hormone pulsatile secretion impairment. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays an important role in the growth, development, maintenance and function of several neuronal systems. Aim of the study: The aim of the study was the evaluation of plasma BDNF concentrations in patients with the diagnosis of FHA. Material and methods. We studied 85 subjects diagnosed with FHA who were compared with 10 healthy, eumenorrheic controls with normal body mass index. Plasma BDNF and serum luteinizing hormone, follicle-stimulating hormone and estradiol (E2) concentrations were measured by immunoenzymatic method (enzyme-linked immunosorbent assay). Results: Significantly lower concentration of plasma BDNF was found in FHA patients (196.31 ± 35.26 pg/ml) in comparison to healthy controls (407.20 ± 25.71 pg/ml; p < 0.0001). In the control group, there was a strong positive correlation between plasma BDNF and serum E2 concentrations (r = 0.92, p = 0.0001) but in FHA group it was not found. Conclusions: Role of BDNF in FHA is not yet fully understood. There could be found studies concerning plasma BDNF concentrations in humans and animals in the literature. However, our study is one of the first projects which describes decreased plasma BDNF concentration in patients with diagnosed FHA. Therefore, further studies on BDNF in FHA should clarify the role of this peptide.
Clinical Features of Elderly Patients Submitted to Coronary Artery Bypass Graft

Objective: To describe the clinical features as well as morbidity and mortality of elderly patients submitted to coronary artery bypass graft (CABG). Design: Randomized, single-center, observational study. Methods: A prospective study was carried out in a tertiary referral teaching hospital (Heart Institute-Brazil). A total of 220 inpatients submitted to elective CABG were evaluated and data collected from the pre-, intra- and postoperative periods. Instruments: The patients were assessed according to the Geriatric Depression Scale. A diagnosis of delirium was determined according to DSM-IV criteria. Results: Of these 220 patients 64.5% were males and 35.5% females. The mean age was 71 years. The most important preoperative findings were a higher incidence of comorbidities such as hypertension (73%), diabetes mellitus (35%), dyslipidemia (27%), and previous myocardial infarction (41%). The majority of patients were found to have three or more vessels obstructed at angiography (74%). The major intraoperative findings were that a high number of the patients received more than 3 grafts (74%). A large proportion (72%) of patients needed a blood transfusion and the overall incidence of clinical complications was 33%. The overall postoperative mortality rate for this observational study was 5%. A large number of patients presented complications (56%) such as hypotension (22%), atrial fibrillation (22%), and delirium (34%). Conclusions: Although elderly patients have a somewhat increased, however acceptable, operative mortality rate, we believe that this patient group can benefit from CABG.
Diet, sensitive periods in flavour learning, and growth

Abstract Diet in early infancy has an impact on early growth and the formation of flavour preferences, as well as on later life health outcomes. Although breast milk is the preferred source of nutrition during infancy, more than half of American infants receive infant formula by the age of 4 months. As a group, formula-fed infants weigh more by the age of one year and have a greater risk for later obesity than breastfed infants. However, a recent randomized study found that, when compared to breastfed infants, infants fed an extensively hydrolysed protein formula (ePHF) had more normative weight gain velocity than infants fed cow's milk formula (CMF). Therefore, grouping all formula-fed infants together with respect to certain health outcomes such as obesity may not be appropriate. Scientific evidence also suggests that there are sensitive periods for flavour learning. Infants become familiar with and learn to accept the flavours they experience through their mother's amniotic fluid and breast milk as well as formula. These early experiences influence flavour preferences of children that may affect food choices and therefore later life health. Further research on the influence of early diet on growth, flavour preferences, and food choices is imperative.
Detecting hydrologic deformation using GRACE and GPS

Hydrological processes cause variations in gravitational potential and surface deformations, both of which are detectable using space geodetic techniques. We computed elastic deformation using continental water load estimates derived from the Gravity Recovery and Climate Experiment and compared to 3D deformation estimated from GPS observations. The agreement is very good in areas where large hydrologic signals occur over broad spatial scales, with correlation in horizontal components as high as 0.9. Agreement is also observed at smaller scales, including across Europe. This suggests that: a) both techniques are perhaps more accurate than previously thought and b) a large percentage of the non‐linear variations seen in our GPS time series are most likely related to geophysical processes rather than analysis error. Low correlation at some sites suggests that local processes or site specific analysis errors dominate the GPS deformation estimates rather than the broad‐scale hydrologic signals detected by GRACE.
Efficacy of Directional Preference Management for Low Back Pain: A Systematic Review

Background Providing specific treatment based on symptom response for people with low back pain (LBP) and a directional preference (DP) is a widely used treatment approach. The efficacy of treatment using the principles of directional preference management (DPM) for LBP is unclear. Objective The purpose of this study was to determine the efficacy of treatment using the principles of DPM for people with LBP and a DP. Methods Computer databases were searched for randomized controlled trials (RCTs) published in English up to January 2010. Only RCTs investigating DPM for people with LBP and a DP were included. Outcomes for pain, back specific function, and work participation were extracted. Results Six RCTs were included in this review. Five were considered high quality. Clinical heterogeneity of the included trials prevented meta-analysis. GRADE quality assessment revealed mixed results; however, moderate evidence was identified that DPM was significantly more effective than a number of comparison treatments for pain, function, and work participation at short-term, intermediate-term, and long-term follow-ups. No trials found that DPM was significantly less effective than comparison treatments. Conclusions Although this systematic review showed mixed results, some evidence was found supporting the effectiveness of DPM when applied to participants with a DP, particularly at short-term and intermediate-term follow-ups. Further high-quality RCTs are warranted to evaluate the effect of DPM applied to people with LBP and a DP.
Dual leadership in complex organizations.

gate rigorously the interrelations of the two (e.g., the physical consequences of movement in social space), and this will in turn enable sociological theory to treat meaningfully the dialectic between the quantitative and the qualitative. In broad outline, these are the directions to which the sociological tradition points. Finally, an existential awareness translated into empirical research will enable sociology better to appreciate and thereby cope with the seemingly "irrational" discontinuities and large-scale upheavals of modern society. Far from abandoning sociology as a science, this is to restore its heritage, grounded in the sociological tradition, of utilizing its global knowledge for socially responsible ends.
A Framework for Emotion Recognition from Human Computer Interaction in Natural Setting

Since human's emotions play a central role in everyday decisions and well-being, developing systems for recognizing and managing human's emotions captured significant research interest in the last decade. However, there is limited research on studying emotion recognition from human-computer interaction (HCI) in natural settings. This work aims at providing a comprehensive study of emotion recognition from HCI, while addressing several remaining challenges in the context of HCI systems. The first challenge incudes the development of HCI emotion recognition models in natural settings instead of lab-controlled settings. The second challenge is to provide a comprehensive collection of potential humans’ interactions with their computers. The third challenge is to provide a meaningful mapping from digital interactions to human related activities, where the mapped activities can then be used as a feature set for accurate emotion recognition models. Hence, the objective of this work is to develop a framework to address these challenges. A robust ground-truth system is defined for the natural capture of a person’s emotion in the context of computer usage while having unobtrusive and seamless data collection. A ground-truth model is designed for emotion recognition by combining facial expressions analysis and selfassessment. New rules are then defined for capturing the digital activity, and then mapping it to human activity that reflects the person’s context and behavior. Finally, the inferred features are used to derive personalized machine learning models for emotion recognition from digital activity. This work also includes a study from real life experiments, where participants were conducting their activity in their natural settings. The inferred features were annotated using the proposed class labels extraction strategy. Finally, a Bayesian Network was used for the emotion recognition model. Results show evidence that it is indeed feasible to sense the user’s emotions through implicit monitoring of everyday computer interactions.
The fate of microbial mutators.

The separation of sex and reproduction in bacteria and most other microbes makes their evolutionary adaptation primarily dependent on mutation as the ‘raw material ’. At first sight, producing as many mutations as possible may thus seem a profitable strategy for microbes, because it would allow them to respond rapidly to changing environmental conditions. However, mutations come in many forms and only very few are beneficial for adaptation of the organism to its environment, while many more have deleterious effects (Sturtevant, 1937). This begs the question to what level the mutation rate should evolve to balance the necessity of adaptive changewith the cost of deleteriousmutations (Sniegowski et al., 2000). Whatever the best mutation rate might be theoretically, actual changes of the mutation rate come about by natural selection acting on mutants with different mutation rates. Since these forces can be different for individual mutation-rate mutants within a population and entire populations of such mutants (see below), the observed mutation rate does not always reflect a single theoretical optimum. Actual mutation rates are rather a product of the interplay between shortand long-term evolutionary forces acting on these mutants, where short-term forces affect the frequency of individual mutation-rate mutants within populations, and long-term forces affect the frequency of populations of these mutants relative to other populations. The clonal structure of most microbial populations causes competition between populations to be a relevant force.