Miracle-dz/UniFAR-FTUs huggingface dataset:
Maximal skin vascular conductance in subjects aged 5-85 yr.

This study examined maximal forearm skin vascular conductance (FVCmax) as a function of age in 74 healthy male and female subjects ranging in age from 5 to 85 yr. The skin temperature of the left forearm was uniformly clamped at 42 degrees C by spraying a fine mist of water over the surface. Forearm blood flow (FBF) was measured by venous occlusion plethysmography (Hg-in-Silastic strain gauge). After 60 min of heating, a reactive hyperemia maneuver was performed to verify that forearm skin blood flow was maximal by using laser Doppler flowmetry to isolate the skin component of FBF. The maximal FBF of each subject was then divided by mean arterial pressure to yield FVCmax (in ml.100 ml-1.min-1.100 mmHg-1), i.e., minimal resistance. The model that best fits the data was curvilinear, as described by FVCmax = 13.1 + 86.9 (age-0.75) (r2 = 0.52, P < 0.001). The exclusion of subjects younger than 18 yr of age simplified the model to a linear fit with a slope of -0.16 conductance units/yr for adults. Interindividual variability remained constant across the entire age span. Once the age effect was considered, there were no significant effects of gender, adiposity, resting blood pressure, physical activity level, or body surface area on FVCmax.
The neurologic syndrome of severe Alzheimer's disease. Relationship to functional decline.

OBJECTIVE To assess the possible association between functional decline and noncognitive neurologic signs in the severe stages of Alzheimer's disease (AD). DESIGN Case series. SETTING Subjects from a dementia research referral center, longitudinally followed, when necessary, into residential home and nursing home settings. PATIENTS A consecutive sample of 56 patients (16 men, 40 women; mean age, 74.6 years) with a clinical diagnosis of probable AD in the moderately severe and severe stages. MAIN OUTCOME MEASURE For global dementia severity, the Global Deterioration Scale and Mini-Mental State examination; for functional assessment, the Functional Assessment Staging Scale; and for assessment of neurologic function, nine release signs (primitive reflexes), 10 measures of extrapyramidal function, and five measures of pyramidal function, including deep-tendon reflexes and plantar signs. Changes in activity or presence of neurologic signs were rated on a seven-point scale. Results were analyzed in terms of prevalence and magnitude of change in relation to functional impairment. RESULTS Prevalence and mean scores of certain release signs, certain extrapyramidal measures commonly referred to as bradykinesia, and certain pyramidal signs showed significant associations with the magnitude of functional impairment. Other neurologic measures, for example, the palmomental reflex, and certain extrapyramidal measures commonly seen in Parkinson's disease, including the glabellar blink reflex, cogwheeling, tremor, shuffling gait, and festination, did not show significant increments with continuing functional decline in AD. CONCLUSIONS Functional decline in the advanced stages of AD appears to be associated with a particular combination of progressive cortical, extrapyramidal, and pyramidal system dysfunction. The characteristics of this neurologic syndrome of the severe stages of AD differ from those of other neurologic disorders. For example, the pattern of extrapyramidal system disease is different from that seen in Parkinson's disease. The neurologic syndrome of the severe stages of AD is amenable to description and deserves further investigation.
Understanding patient experience: a deployment study in cardiac remote monitoring

The term 'patient experience' is currently part of a global discourse on ways to improve healthcare. This study empirically explores what patient experience is in cardiac remote monitoring and considers the implications for user experience (UX). Through interviews around the deployment of a mobile app that enables patients to collaborate with clinicians, we unpack experiences in six themes and present narratives of patients' lifeworlds. We find that patients' emotions are grounded in negative feelings (uncertainty, anxiety, loss of hope) and that positive experiences (relief, reassurance, safety) arise from getting feedback on symptoms and from continuous and comforting interaction with clinicians. With this paper, we aim to sensitise UX researchers and designers of patient-centred e-health by proposing three UX dimensions: connectedness, comprehension, and compassion.
An Empirical Analysis of Social Dimension Factors Towards Better IT Service Quality for Malaysian Public Agencies

Information technology (IT) has become an important part in enabling business decisions and strategies in organizations. The IT unit established in various organizations is responsible to ensure that different business units receive the expected level of technical assistance which they require. However, in many cases, the common understanding between business and IT is rarely achieved. This leads to the debate on how business and IT can be aligned in ensuring better IT services is provided to the end-users. Hence, there is a need to identify critical social factors that lead to better alignment thus leads to better service quality. This paper aims to conceptualize how business-IT alignment would have the impact to IT services through the social aspects of cognition, shared knowledge, and communication. A model is derived from the findings of the literatures and tested within the domain of the Malaysian agriculture public sectors using quantitative method. Results indicate that there are positive impacts of social dimensions towards business-IT alignment and thus has a significant impact towards IT service quality. This model reveals the insight on the importance of social alignment dimension factors in achieving better IT service quality in government agency setting.
Evaluation of gene targeting by homologous recombination in ovine somatic cells

Mouse models for some human genetic diseases are limited in their applications since they do not accurately reproduce the phenotype of the human disease. It has been suggested that larger animals, for example sheep, might produce more useful models, as some aspects of sheep physiology and anatomy are more similar to those of humans. The development of methods to clone animals from somatic cells provides a potential novel route to generate such large animal models following gene targeting. Here, we assess targeting of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in ovine somatic cells using homologous recombination (HR) of targeting constructs with extensive (>11 kb) homology. Electroporation of these constructs into ovine fetal and post‐natal fibroblasts generated G418‐resistant clones, but none analyzed had undergone HR, suggesting that at least for this locus, it is an extremely inefficient process. Karyotyping of targeted ovine fetal fibroblasts showed them to be less chromosomally stable than post‐natal fibroblasts, and, moreover, extended culture periods caused them to senesce, adversely affecting their viability for use as nuclear transfer donor cells. These data stress the importance of donor cell choice in somatic cell cloning and suggest that culture time be kept to a minimum prior to nuclear transfer in order to maximize cell viability. Mol. Reprod. Dev. 66: 115–125, 2003. © 2003 Wiley‐Liss, Inc.
Saving the breeds: German Farmers’ preferences for Endangered Dairy Breed conservation programs

Animal genetic diversity is a unique and irreplaceable heritage. Globally, about 20 % of all breeds or livestock populations are considered to be ‘at risk’ and 9 % are already extinct. On farm, the concentration on elite breeding lines has endangered a number of alternative breeds. In Germany, over half of the entire dairy cattle population belongs to only three dominant breeds. Although several alternative breeds are well known for superior functional characteristics like e.g. a good fertility, an excellent udder health, and their ability to adapt to diverse environments, they are increasingly replaced by Holstein cows due to higher milk performances. To design effective incentive schemes that encourage farmers to maintain desired breeds, it is crucially important to know about their preferences for certain contract components. A discrete choice experiment (DCE) with 160 dairy cattle breeders revealed determinants of farmers’ willingness to accept conservation contracts to conserve rare German cattle breeds like Red dual-purpose cattle or Angler cattle. We included attributes like the monitoring of pairing, requirements for the keeping conditions, a collective bonus for an increase in population by five percent and the contract length in our experimental design. A Random Parameter Logit (RPL) model revealed that farmers favor shorter contracts (one or five years), a bonus for a population increase and the requirement of outdoor access. In contrast, farmers rather reject to choose a contract that requires participation in a breeding program and the prohibition of slatted floors. Two distinctive classes of farmers can be identified based on the results of a Latent Class Model (LCM). Organic farmers are generally less likely to join a program and are even more disapproving contracts where the pairing is monitored by the breeding association. However, it seems that program requirements should not be too restrictive on the farm management and rather focus on the compensation of associated income loss.
Migration and employment change: empirical evidence on the spatial and temporal dimensions of the linkage.

"This paper uses a unique set of [U.S.] data to estimate the magnitude of the linkages between employment changes and net employment migration. A simple simultaneous system is specified and estimated for 17 consecutive years. In an average year two extra jobs attract about one additional net migrant, and one additional net migrant has a direct effect on area employment of almost 1.4 jobs. " The data are from the One-Percent Social Security Continuous Work History Sample and are for the years 1958 to 1975. The changes in this relationship over time as the economic situation varies are analyzed.
Operational Momentum During Ordering Operations for Size and Number in 4-Month-Old Infants

An Operational Momentum (OM) effect is shown by 9-month-old infants during non-symbolic arithmetic, whereby they overestimate the outcomes to addition problems, and underestimate the outcomes to subtraction problems. Recent evidence has shown that this effect extends to ordering operations for size-based sequences in 12-month-olds. Here we provide evidence that OM occurs for ordering operations involving numerical sequences containing multiple quantity cues, but not size-based sequences, already at 4 months of age. Infants were tested in an ordinal task in which they detected and represented increasing or decreasing variations in physical and/or numerical size, and then responded to ordinal sequences that exhibited greater or lesser sizes/numerosities, thus following or violating the OM generated during habituation. Results showed that OM was absent during size ordering (Experiment 1), but was present when infants ordered arrays of discrete elements varying on numerical and non-numerical dimensions, if both number and continuous magnitudes were available cues to discriminate between with-OM and against-OM sequences during test trials (Experiments 2 vs. 3). The presence of momentum for ordering number only when provided with multiple cues of magnitude changes suggests that OM is a complex phenomenon that blends multiple representations of magnitude early in infancy.
Mortality of Workers Occupationally Exposed to Refractory Ceramic Fibers

This study was prompted by refractory ceramic fibers (RCF) inhalation studies at high dose levels in animals that demonstrated positive effects for lung fibrosis, mesothelioma, and lung cancer. Current and former male workers employed between 1952 and 2000 at two RCF manufacturing facilities were followed to investigate a possible excess in mortality. The mortality analytic methods included: (1) standardized mortality ratios comparing this cohort to the general and state populations, and (2) a proportional hazards model that relates risk of death to the lifetime cumulative fiber-months/cc exposure among the RCF cohort, adjusted for age at hire and for race. There was no excess mortality related to all deaths, all cancers, or malignancies or diseases of the respiratory system including mesothelioma, but there was a statistically significant association with cancers of the urinary organs SMR = 344.8 (95% CL of 111.6, 805.4). The quality of the data for job history, exposure, and smoking history were very high. Although the cohort was relatively small and young with an average age of 51, the mean latency period was over 21 years. Because of these limitations, the preliminary findings warrant the continuation of this mortality registry for future analyses.
Inference for Causal Interactions for Continuous Exposures under Dichotomization

Summary Dichotomization of continuous exposure variables is a common practice in medical and epidemiological research. The practice has been cautioned against on the grounds of efficiency and bias. Here we consider the consequences of dichotomization of a continuous covariate for the study of interactions. We show that when a continuous exposure has been dichotomized certain inferences concerning causal interactions can be drawn with regard to the original continuous exposure scale. Within the context of interaction analyses, dichotomization and the use of the results in this article can furthermore help prevent incorrect conclusions about the presence of interactions that result simply from erroneous modeling of the exposure variables. By considering different dichotomization points one can gain considerable insight concerning the presence of causal interaction between exposures at different levels. The results in this article are applied to a study of the interactive effects between smoking and arsenic exposure from well water in producing skin lesions.
Fluvastatin inhibits activation of JAK and STAT proteins in diabetic rat glomeruli and mesangial cells under high glucose conditions

AbstractAim:The aim of the present study was to further elucidate the mechanism of the protective role of fluvastatin on diabetic nephropathy.Methods:Streptozotocin-induced diabetic rats were treated daily with fluvastatin (4 mg/kg body weight) by gavage. The animals were killed 4 weeks later and urine and blood samples were collected. The kidney tissues were removed and subjected to the following experiments. Rat glomerular mesangial cells (GMC) were cultured under normal glucose (5.5 mmol/L), high glucose (HG, 30 mmol/L), HG+AG490 (10 μmol/L), or HG with fluvastatin (1 μmol/L). Glomeruli or the GMC lysate was immunoprecipitated and/or immunoblotted with antibodies against Janus kinase 2 (JAK2), SH2-domain containing tyrosine phosphatase-1 (SHP-1), phosphospecific SHP-2, and signal transducer and activators of transcription (STAT), respectively. Transforming growth factor-β (TGF-β1) mRNA was measured by RT-PCR. The protein synthesis of TGF-β1 and fibronectin in the culture medium of GMC was detected by ELISA.Results:The phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 increased significantly, and SHP-1 phosphorylation was reduced in glomeruli of diabetic rats. Treatment with fluvastatin reduced phosphorylation levels of JAK2, STAT1, STAT3, and SHP-2 in glomeruli of diabetic rats, but it had no effect on the dephosphorylation of SHP-1. The exposure of GMC to 30 mmol/L glucose caused the activation of JAK2, STAT1, STAT3, and SHP-2. It upregulated TGF-β1 expression and increased protein synthesis of fibronectin. These high glucose-induced changes were suppressed by fluvastatin, as well as AG490, a JAK2 inhibitor.Conclusion:The regulation of the phosphorylation of JAK/STAT by fluvastatin may be responsible for its renal protective effects on diabetic nephropathy.
Two central core disease (CCD) deletions in the C‐terminal region of RYR1 alter muscle excitation–contraction (EC) coupling by distinct mechanisms

Central core disease (CCD) and malignant hyperthermia (MH) are skeletal muscle disorders that are linked to mutations in the gene that encodes the type 1 ryanodine receptor (RYR1). The RYR1 ion channel plays a central role in excitation–contraction (EC) coupling by releasing Ca2+ from an internal store. Pathogenic CCD mutations in RYR1 result in changes in the magnitude of Ca2+ release during EC coupling. CCD has recently been linked to two novel deletions (c.12640_12648delCGCCAGTTC [p.Arg4214_Phe4216del] and c.14779_14784delGTCATC [p.Val4927_Ile4928del]) in the C‐terminal region of RYR1. To determine the phenotypic consequences of these mutations and extend our understanding of the pathogenic mechanisms that underlie CCD, we determined functional effects on Ca2+ release channel activity of analogous deletions (p.Arg4215_Phe4217del and p.Val4926_Ile4927del) engineered into rabbit RYR1 following expression in RYR1‐null (dyspedic) myotubes and HEK293 cells. In addition, we assessed effects of the p.Arg4214 Phe4216del mutation on RYR1 function in lymphoblastoid cells obtained from CCD patients heterozygous for the mutation. Here we report that both deletions significantly reduce Ca2+ release following RYR1 activation, but by different mechanisms. While the p.Arg4214_Phe4216del deletion promotes Ca2+ depletion from intracellular stores by exhibiting a classic “leaky channel” behavior, the p.Val4927_Ile4928del deletion reduces Ca2+ release by disrupting Ca2+ gating and eliminating Ca2+ permeation through the open channel. Hum Mutat 28(1), 61–68, 2007. Published 2006 Wiley‐Liss, Inc.
Effects of Orthostatism and Hemodialysis on Mean Heart Period and Fractal Heart Rate Properties of Chronic Renal Failure Patients

The aim of this work was to evaluate the short-term fractal index (α1 ) of heart rate variability (HRV) in chronic renal failure (CRF) patients by identifying the effects of orthostatism and hemodialysis (HD), and by evaluating the correlation between α1 and the mean RR interval from sinus beats (meanNN). HRV time series were derived from ECG data of 19 CRF patients and 20 age-matched healthy subjects obtained at supine and orthostatic positions (lasting 5 min each). Data from CRF patients were collected before and after HD. α1 was calculated from each time series and compared by analysis of variance. Pearson's correlations between meanNN and α1 were calculated using the data from both positions by considering three groups: healthy subjects, CRF before HD and CRF after HD. At supine position, α1 of CRF patients after HD (1.17 ± 0.30) was larger (P < 0.05) than in healthy subjects (0.89 ± 0.28) but not before HD (1.10 ± 0.34). α1 increased (P < 0.05) in response to orthostatism in healthy subjects (1.29 ± 0.26) and CRF patients after HD (1.34 ± 0.31), but not before HD (1.25 ± 0.37). Whereas α1 was correlated (P < 0.05) with the meanNN of healthy subjects (r = -0.562) and CRF patients after HD (r = -0.388), no significance in CRF patients before HD was identified (r = 0.003). Multiple regression analysis confirmed that α1 was mainly predicted by the orthostatic position (in all groups) and meanNN (healthy subjects and patients after HD), showing no association with the renal disease condition in itself. In conclusion, as in healthy subjects, α1 of CRF patients correlates with meanNN after HD (indicating a more irregular-like HRV behavior at slower heart rates). This suggests that CRF patients with stable blood pressure preserve a regulatory adaptability despite a shifted setting point of the heart period (i.e., higher heart rate) in comparison with healthy subjects.
Regulatory Competition in Banking: A General Equilibrium Approach

We study competition between governments with regard to capital requirements, bank levies and resolution regimes in a general equilibrium setting. In a two-country model, households can invest both domestically and abroad, with banks acting as intermediaries between households and risky technologies. When competing governments set banking regulation, the mechanism at work is driven by the trade-off between accentuating benefits over costs stemming from banking activities, on the one hand, and enhancing banks' competitiveness, on the other hand. Whether or not regulatory competition yields the efficient allocation of resources and risks crucially depends on whether governments compete with one, two or three policy tools.
Pharmacokinetics of meropenem in intensive care unit patients receiving continuous veno‐venous hemofiltration or hemodiafiltration

Objective: To evaluate an intravenous meropenem dosage regimen in adult intensive care patients with acute renal failure treated by continuous renal replacement therapy. Design: A prospective, clinical study. Setting: General intensive care unit of a university hospital. Patients: Ten critically ill adult patients being treated with meropenem and receiving continuous veno‐venous hemofiltration (hemofiltration rates, 1‐2 L/hr) (n = 5) or continuous veno‐venous hemodiafiltration (hemofiltration rates, 1‐1.5 L/hr; dialysis rates, 1‐1.5 L/hr) (n = 5) via a polyacrylonitrile hollow fiber 0.9‐m2 filter. Interventions: Patients received a meropenem dose of 1 g iv every 12 hrs as a 5‐min bolus. Measurements and Main Results: Meropenem concentrations were measured by high‐performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration‐time profiles, derive pharmacokinetic variable estimates, and determine sieving coefficients and filter clearances. The serum concentrations were examined to see whether they were above the minimum inhibitory concentrations (MICs) for pathogens that may be encountered in intensive care patients. Serum concentrations exceeded 4 mg/L (MIC90 for Pseudomonas aeruginosa) during 67% of the dosage period in all patients. Sub‐MIC90 concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after treatment. Mean (SD) (n = 10) pharmacokinetic variable estimates were as follows: elimination half‐life, 5.16 hrs (1.83 hrs); volume of distribution, 0.35 L/kg (0.10 L/kg); and total clearance, 4.30 L/hr (1.38 L/hr). A sieving coefficient of 0.93 (0.06) (n = 9) indicated free flow across the filter. The fraction cleared by the extracorporeal route was 48% (13%) (n = 9), which is clinically important. Conclusions: A meropenem dose of 1 g iv every 12 hrs provides adequate serum concentrations in the majority of patients receiving continuous veno‐venous hemofiltration or continuous veno‐venous hemofiltration with a 0.9‐m2 polyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of up to 3 L/hr. A lower dose would not be sufficient for the empirical treatment of potentially life‐threatening infections in all patients.