Miracle-dz/UniFAR-FTUs huggingface dataset:
Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates.

INTRODUCTION The degree of generalisability of patient databases to the general population is important for interpreting database research. This report describes the representativeness of The Health Improvement Network (THIN), a UK primary care database, of the UK population. METHODS Demographics, deprivation (Townsend), Quality and Outcomes Framework (QOF) condition prevalence and deaths from THIN were compared with national statistical and QOF 2006/2007 data. RESULTS Demographics were similar although THIN contained fewer people aged under 25 years. Condition prevalence was comparable, e.g. 3.5% diabetes prevalence in THIN, 3.7% nationally. More THIN patients lived in the most affluent areas (23.5% in THIN, 20% nationally). Between 1990 and 2009, standardised mortality ratio ranged from 0.81 (95% CI: 0.39-1.49; 1990) to 0.93 (95% CI: 0.48-1.64; 1995). Adjusting for demographics/deprivation, the 2006 THIN death rate was 9.08/1000 population close to the national death rate of 9.4/1000 population. CONCLUSION THIN is generalisable to the UK for demographics, major condition prevalence and death rates adjusted for demographics and deprivation.
Identification and validation of microRNAs as endogenous controls for quantitative polymerase chain reaction in plasma for stable coronary artery disease.

BACKGROUND Circulating microRNAs (miRNAs) have been proved to serve as biomarkers for diagnosis and assessment of prognosis of coronary artery disease (CAD). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) is a widely-used technique to estimate expression levels of circulating miRNAs. Selection of optimal endogenous control (EC) remains critical to obtain reliable qPCR data of miRNAs expression. However, reference controls for normalization of circulating miRNA in CAD are still lacking. The purpose of this study was to identify stably expressed miRNAs to normalize RT-qPCR data derived from plasma in stable CAD. METHODS We identified 10 stably expressed candidate ECs by combining miRNA microarray screening and literature screening. These 10 candidate ECs were estimated by RT-qPCR and the data were analyzed by NormFinder and BestKeeper algorithm. RESULTS Two most stable ECs were identified as EC candidates and they were subsequently validated in another larger cohort. The 2 candidates were also validated by normalizing the expression levels of miR-21. In general, they were superior to the commonly used reference gene RNU6 in quantification cycle (Cq) value, stability value and normalization effect. CONCLUSIONS Our results demonstrated that miR-6090 and miR-4516 can be used as reference genes for plasma miRNA analysis in stable CAD.
Temporal strategy and performance during a fatiguing short-cycle repetitive task

This study investigated temporal changes in movement strategy and performance during fatiguing short-cycle work. Eighteen participants performed six 7-min work blocks with repetitive reaching movements at 0.5 Hz, each followed by a 5.5-min rest break for a total duration of 1 h. Electromyography (EMG) was collected continuously from the upper trapezius muscle, the temporal movement strategy and timing errors were obtained on a cycle-to-cycle basis, and perceived fatigue was rated before and after each work block. Clear signs of fatigue according to subjective ratings and EMG manifestations developed within each work block, as well as during the entire hour. For most participants, timing errors gradually increased, as did the waiting time at the near target. Changes in temporal movement strategy were negatively correlated with changes in the level and variability of EMG, suggesting that an adaptive temporal strategy offset the development of unstable motor solutions in this fatiguing, short-cycle work. Practitioner Summary: Sustained performance of operators is essential to maintain competitiveness. In this study of repetitive work, participants gradually changed their temporal movement strategy, for possibly alleviating the effects of fatigue. This suggests that in order to effectively counteract fatigue and sustain performance, industrial production should allow extensive spatial and temporal flexibility.
Cumulative evaluation of a quantitative immunochemical fecal occult blood test to determine its optimal clinical use

Quantified, human hemoglobin (Hb)‐specific, immunochemical fecal occult blood test (IFOBT) measurements are now used for colorectal cancer (CRC) screening. The objective was to evaluate sensitivity and specificity for CRC and advanced adenomatous polyps (APs) by the fecal Hb threshold used to determine a positive test and the number of IFOBTs prepared per test, so as to determine the least number of colonoscopies required to detect a neoplasm.
Integration of cognitive allocentric information in visuospatial short‐term memory through the hippocampus

Visuospatial short‐term memory relies on a widely distributed neocortical network: some areas support the encoding process of the visually acquired spatial information, whereas other ares are more involved in the active maintenance of the encoded information. Recently, in a pointing to remembered targets task, it has been shown in healthy subjects that, for memory delays of 5 s, spatial errors are affected also by cognitive allocentric information, i.e., covert spatial information derived from a pure mental representation. We tested the effect of a lesion of the hippocampus on the accuracy of pointing movements toward remembered targets, with memory delays falling in the 0.5–30 s range. The spatial distributions of the two target sets we used (line and left‐right) allowed the exploitation of cognitive allocentric spatial information: both sets were in the frontal plane, the line one being composed by eleven points distributed uniformly along a virtual line tilted 45° away from the vertical, whereas the left‐right set was composed by two workspaces symmetrically distributed at the extremes of a horizontal virtual line. We have found a significant difference between the performance of three hippocampal amnesic subjects and a group of normal controls for delays equal to or longer than 15 s, the difference being along the allocentric axis, i.e., the direction of the virtual line defined by the target set. On this basis we suggest that the hippocampal formation may enhance the spatial information processed within short‐term memory with cognitive allocentric information. The association that may be operated through the neocortical‐hippocampal loop of the newly acquired spatial information with well established spatial cognitive items could affect the precision of the short‐term memory storage for memory delays exceeding about 15 s and might be the result of a modulation of the span of the spatial memory buffer along context‐specific directions. © 2005 Wiley‐Liss, Inc.
The Bramble Bush: The Classic Lectures on the Law and Law School

Introduction to the Oxford Edition: The Bramble Bush and You by Steve Sheppard Foreword (1950 Edition) Preface (1930 Edition) Acknowledgments (1950 Edition) Acknowledgments (1930 (Edition) Part One: The Bramble Bush Chapter I What Law Is About Chapter II This Case System: What Lies Behind the Case Chapter III This Case System: What to Do with the Cases Chapter IV This Case System: Precedent Chapter V Ships and Shoes and Sealing Wax Chapter VI And Law School Offers What? Part Two: The Other Side Chapter VII Law and Civilization Chapter VIII Beyond Bread and Butter Chapter IX The Second Year Chapter X Before Sunrise They That Come After Afterword Index
Arabidopsis β-Ketoacyl-[Acyl Carrier Protein] Synthase I Is Crucial for Fatty Acid Synthesis and Plays a Role in Chloroplast Division and Embryo Development[C][W][OA]

Arabidopsis β-ketoacyl-[acyl carrier protein] synthase I (KASI) catalyzes the elongation of de novo fatty acid synthesis. Deficiency of KASI results in multiple morphological defects and suppresses chloroplast division at early stages of leaf development. This finding indicates the important roles of polar lipid supply for chloroplast division and development. Lipid metabolism plays a pivotal role in cell structure and in multiple plant developmental processes. β-Ketoacyl-[acyl carrier protein] synthase I (KASI) catalyzes the elongation of de novo fatty acid (FA) synthesis. Here, we report the functional characterization of KASI in the regulation of chloroplast division and embryo development. Phenotypic observation of an Arabidopsis thaliana T-DNA insertion mutant, kasI, revealed multiple morphological defects, including chlorotic (in netted patches) and curly leaves, reduced fertility, and semidwarfism. There are only one to five enlarged chloroplasts in the mesophyll cells of chlorotic sectors of young kasI rosette leaves, indicating suppressed chloroplast division under KASI deficiency. KASI deficiency results in a significant change in the polar lipid composition, which causes the suppressed expression of FtsZ and Min system genes, disordered Z-ring placement in the oversized chloroplast, and inhibited polymerization of FtsZ protein at mid-site of the chloroplast in kasI. In addition, KASI deficiency results in disrupted embryo development before the globular stage and dramatically reduces FA levels (~33.6% of the wild type) in seeds. These results demonstrate that de novo FA synthesis is crucial and has pleiotropic effects on plant growth. The polar lipid supply is important for chloroplast division and development, revealing a key function of FA synthesis in plastid development.
Analysis and Design of Cognitive Radio Networks and Distributed Radio Resource Management Algorithms

Cognitive radio is frequently touted as a platform for implementing dynamic distributed radio resource management algorithms. In the envisioned scenarios, radios react to measurements of the network state and change their operation according to some goal driven algorithm. Ideally this flexibility and reactivity yields tremendous gains in performance. However, when the adaptations of the radios also change the network state, an interactive decision process is spawned and once desirable algorithms can lead to catastrophic failures when deployed in a network. This document presents techniques for modeling and analyzing the interactions of cognitive radio for the purpose of improving the design of cognitive radio and distributed radio resource management algorithms with particular interest towards characterizing the algorithms' steady-state, convergence, and stability properties. This is accomplished by combining traditional engineering and nonlinear programming analysis techniques with techniques from game to create a powerful model based approach that permits rapid characterization of a cognitive radio algorithm's properties. Insights gleaned from these models are used to establish novel design guidelines for cognitive radio design and powerful low-complexity cognitive radio algorithms. This research led to the creation of a new model of cognitive radio network behavior, an extensive number of new results related to the convergence, stability, and identification of potential and supermodular games, numerous design guidelines, and several novel algorithms related to power control, dynamic frequency selection, interference avoidance, and network formation. It is believed that by applying the analysis techniques and the design guidelines presented in this document, any wireless engineer will be able to quickly develop cognitive radio and distributed radio resource management algorithms that will significantly improve spectral efficiency and network and device performance while removing the need for significant post-deployment site management.
Comparison of the A2 Gene Locus in Leishmania donovani and Leishmania major and Its Control over Cutaneous Infection*

In Old World Leishmania infections, Leishmania donovani is responsible for fatal visceral leishmaniasis, and L. major is responsible for non-fatal cutaneous leishmaniasis in humans. The genetic differences between these species which govern the pathology or site of infection are not known. We have therefore carried out detailed analysis of the A2 loci in L. major and L. donovani because A2 is expressed in L. donovani but not L. major, and A2 is required for survival in visceral organs by L. donovani. We demonstrate that although L. major contains A2 gene regulatory sequences, the multiple repeats that exist in L. donovani A2 protein coding regions are absent in L. major, and the remaining corresponding A2 sequences appear to represent non-expressed pseudogenes. It was possible to restore amastigote-specific A2 expression to L. major, confirming that A2 regulatory sequences remain functional in L. major. Although L. major is a cutaneous parasite in rodents and humans, restoring A2 expression to L. major inhibited its ability to establish a cutaneous infection in susceptible BALB/c or resistant C57BL6 mice, a phenotype typical of L. donovani. There was no detectable cellular immune response against L. major after cutaneous infection with A2-expressing L. major, suggesting that the lack of growth was not attributable to acquired host resistance but to an A2-mediated suppression of parasite survival in skin macrophages. These observations argue that the lack of A2 expression in L. major contributed to its divergence from L. donovani with respect to the pathology of infection.
A direct relationship between plasma aldosterone and cardiac L‐type Ca2+ current in mice

Aldosterone is involved in a variety of pathophysiological processes that ultimately cause cardiovascular diseases. Despite this, the physiological role of aldosterone in heart function remains elusive. We took advantage of transgenic mouse models characterized by a renal salt‐losing (SL) or salt‐retaining (SR) phenotype, thus exhibiting chronically high or low plasma aldosterone levels, respectively, to investigate the chronic effects of aldosterone in cardiomyocytes devoid of pathology. On a diet containing normal levels of salt, these animals do not develop any evidence of cardiovascular disease. Using the whole cell patch‐clamp technique on freshly isolated adult ventricular cardiomyocytes, we observed that the amplitude of L‐type Ca2+ currents (ICa) correlates with plasma aldosterone levels. Larger values of ICa are associated with high aldosterone concentrations in SL models, whereas smaller values of ICa were observed in the SR model. Neither the time‐ nor the voltage‐dependent properties of ICa varied measurably. In parallel, we determined whether modulation of ICa by blood concentration of aldosterone has a major physiological impact on the excitation–contraction coupling of the cardiomyocytes. Action potential duration, [Ca2+]i transient amplitude and contraction are increased in the SL model and decreased in the SR model. In conclusion, we demonstrate that the blood concentration of aldosterone exerts chronic regulation of ICa in mouse cardiomyocytes. This regulation has important consequences for excitation–contraction coupling and, potentially, for other Ca2+‐regulated functions in cardiomyocytes.
Severe Pain Confounds Neuropsychological Test Performance

There is little information on the effect of pain on neuropsychological test performance. We have undertaken this study to explore which tests are affected by pain, the magnitude of these changes, and other confounders of neuropsychological performance in a population of patients having spine surgery. Twenty-four elderly English speaking Caucasian patients (age > 60 years) were enrolled pre-operatively in this Institutional Review Board approved study. Pain scores using an 11-point Numeric Pain Intensity scale and performance on a neuropsychological battery (Controlled Oral Word Association, Rey Complex Figure, Trails A and B) were assessed at two times, before and one day after surgery. Scores were calculated using the standard algorithms and change scores were calculated by subtracting the baseline from follow-up scores. After surgery, performance on the Rey Complex Figure (r = –0.577, p = 0.004) and Trails Part A (r = 0.527, p = 0.01) declined with increasing post-operative pain scores. Women reported higher pain scores post-operatively than men (p = 0.046), and performed worse than men for change in performance on Trails Part A (p = 0.027). These data suggest that pain can influence performance on certain cognitive tests, and that some gender differences in these effects may occur. Interpretation of performance measures should take into account possible effects of pain, although our understanding of pain effects and ability to predict them in individual people, currently are quite limited.
Aggregation of congeneric parasites (Monogenea: Dactylogyrus) among gill microhabitats within one host species (Rutilus rutilus L.)

Parasite aggregation within the gill arches of 1 host species (Rutilus rutilus L.) was studied in the case of 9 congeneric monogeneans belonging to the genus Dactylogyrus. Both intra- and interspecific aggregation were followed by considering gill arches as independent patches. Parasite species were found to be aggregated both intra- and interspecifically. We showed that the intensity of parasite infection was positively related to intraspecific aggregation only for the more abundant species. No relationship was found between intensity of parasite infection and niche size when correcting for total parasite intensity. This may suggest that when parasite intensities are low, intraspecific competition may not have a strong effect on parasites. Conversely, when looking at the evolution of niche size and intraspecific aggregation for each species separately, intraspecific aggregation decreased for the most abundant species (D. crucifer) suggesting that this species is more competitive than others when total parasite intensity increases. When considering interspecific aggregation, Dactylogyrus species were found to be positively and negatively aggregated. Following the prediction of morphological and ecological similarity for congeneric species, Dactylogyrus species similar in morphometry of attachment parts tend to be more positively aggregated among their gill microhabitats than Dactylogyrus species with morphometric differences in attachment parts.
Water–fat separation with IDEAL gradient‐echo imaging

To combine gradient‐echo (GRE) imaging with a multipoint water–fat separation method known as “iterative decomposition of water and fat with echo asymmetry and least squares estimation” (IDEAL) for uniform water–fat separation. Robust fat suppression is necessary for many GRE imaging applications; unfortunately, uniform fat suppression is challenging in the presence of B0 inhomogeneities. These challenges are addressed with the IDEAL technique.
Physicochemical Characterization of El Tor Vibriophage S20

Objective:To characterize Vibrio cholerae El Tor typing phage S20 (ATCC No. 51352-B3). Methods and Results: The phage has a hexagonal head and a short tail. Cryo-electron microscopy and three-dimensional image reconstruction showed that the phage head has icosahedral symmetry. The phage has two major structural polypeptides of 50 and 42 kDa. Adsorption of the phage to its host followed a biphasic kinetics and its intracellular growth is characterized by a latent period of 12 min and a burst size of around 60 particles per infected cell. The phage was found to be stable at a pH range 5.0–9.0 and moderately thermotolerant and highly UV sensitive. Phage genome comprises a 40.7 ± 1.5-kb linear DNA molecule with random circular permutation and terminal redundancy. The restriction endonucleases AccI, HpaII, HaeIII, HindIII, EcoRV, HincII, DraI and XmnI cut vibriophage S20 DNA. Conclusion: Vibriophage S20, which belongs to Podoviridae, has an icosahedral head and the genome, which is double-stranded linear DNA, has random circular permutation and terminal redundancy.
Enhancements of force-torque map based assembly applied to parallel robots

This article presents the application and enhancements of assembly strategies using force-torque maps in view of parallel robots. Starting from classical assembly strategies the fundamentals of force-torque maps are briefly discussed. Taking up the core idea, a strategy for assembling objects by parallel robots is proposed, where frictional effects are reduced by an enhanced force and position control. Special attention is paid to acquisition of force-torque maps with respect to parameter sensitivity. Practical issues are pointed out and discussed in view of industrial applications. A quality assessment of force-torque maps based on a redundancy index is introduced hinting at the performance and possibilities of optimization of the assembly strategy.
Subclinical atherosclerosis modeling: Integration of coronary artery calcium score to framingham equation

Medical prevention consists to identify as soon as possible apparently healthy individuals who develop a disease and to engage them for active preventive treatment. Several cross-sectional studies of general populations or high cardiovascular risk have shown that coronary calcium score (coronary artery calcium, CAC) was positively associated with traditional risk factors (hypertension, dyslipidemia, diabetes, and smoking) and some new risk factors (fibrinogen). In this work, we first calculated, among 618 men, the risk of 10-years cardiovascular heart disease (CHD) according to the Framingham risk model, and then we calculated the probability that the CAC score of an individual falls in all four CAC categories (0, 1-100, 101-400 and > 400). We obtained risk factors adjusted relative risk (RR) estimates from a meta-analysis comparing the risk of coronary heart disease in individuals with CAC scores of 1-100 (RR = 3D 1.7), 101 - 400 (RR = 3D 3.0) and> 400 (RR = 3D 4.3) with the risk of a person with a CAC score zero. The new model for the risk of CHD for each CAC score category were then calculated assuming an average 1-year risk of CHD and risk assessment of the four CAC score categories, weighted by the probability that scores fall into each category. The combination of modeling the CCA with the modeling of conventional risk factors allows obtaining a remarkable predictive value that can improve the assessment of overall risk Framingham through the reclassification of the risk of CHD to an extent which may be clinically important.
Perturbation Analysis: A Simple Method for Filtering SNPs with Erroneous Genotyping in Genome‐Wide Association Studies

We introduce a simple and yet scientifically objective criterion for identifying SNPs with genotyping errors due to poor clustering. This yields a metric for assessing the stability of the assigned genotypes by evaluating the extent of discordance between the calls made with the unperturbed and perturbed intensities. The efficacy of the metric is evaluated by: (1) estimating the extent of over‐dispersion of the Hardy‐Weinberg equilibrium chi‐square test statistics; (2) an interim case‐control study, where we investigated the efficacy of the introduced metric and standard quality control filters in reducing the number of SNPs with evidence of phenotypic association which are attributed to genotyping errors; (3) investigating the call and concordance rates of SNPs identified by perturbation analysis which have been genotyped on both Affymetrix and Illumina platforms. Removing SNPs identified by the extent of discordance can reduce the degree of over‐dispersion of the HWE test statistic. Sensible use of perturbation analysis in an association study can correctly identify SNPs with problematic genotyping, reducing the number required for visual inspection. SNPs identified by perturbation analysis had lower call and concordance rates, and removal of these SNPs significantly improved the performance for the remaining SNPs.