Miracle-dz/UniFAR-FTUs huggingface dataset:
Folic acid supplementation and the occurrence of congenital heart defects , orofacial clefts , multiple births , and miscarriage 1 – 3

Key research findings relative to the question of whether maternal use of folic acid before and during pregnancy reduces the chance that offspring will be born with a congenital heart defect or an orofacial cleft are reviewed in this paper. Observational studies in general support an association between maternal use of multivitamins containing folic acid and a reduction in the occurrence of congenital heart defects and orofacial clefts. Results from one randomized controlled trial (RCT) provide the strongest evidence that multivitamins prevent congenital heart defects, but this RCT did not provide evidence that multivitamins prevent orofacial clefts. In addition, most observational and interventional studies are not designed to detect an independent effect from folic acid. Early studies suggested that periconceptional multivitamin use was associated with an increased occurrence of both miscarriages and multiple births, which has resulted in a great deal of controversy about the safety of folic acid use during pregnancy. We also review reports that were designed to answer these questions with more definitive data. When more substantial evidence about the effect of periconceptional folic acid on the occurrence of congenital heart defects and orofacial clefts is reported, we will have additional support for promoting folic acid intervention programs. All women capable of becoming pregnant should continue to consume 400 g/d of folic acid in addition to a healthy diet as advised. Am J Clin Nutr 2005;81(suppl):
Critical physicochemical and biological attributes of nanoemulsions for pulmonary delivery of rifampicin by nebulization technique in tuberculosis treatment

Abstract The study investigated aerosolization, pulmonary inhalation, intracellular trafficking potential in macrophages and pharmacokinetics profiles of rifampicin-oleic acid first-generation nanoemulsion and its respective chitosan- and chitosan-folate conjugate-decorated second and third-generation nanoemulsions, delivered via nebulization technique. The nanoemulsions were prepared by conjugate synthesis and spontaneous emulsification techniques. They were subjected to physicochemical, drug release, aerosolization, inhalation, cell culture and pharmacokinetics analysis. The nanoemulsions had average droplet sizes of 40–60 nm, with narrow polydispersity indices. They exhibited desirable pH, surface tension, viscosity, refractive index, density and viscosity attributes for pulmonary rifampicin administration. All nanoemulsions demonstrated more than 95% aerosol output and inhalation efficiency greater than 75%. The aerosol output, aerosolized and inhaled fine particle fractions were primarily governed by the size and surface tension of nanoemulsions in an inverse relationship. The nanoemulsions were found to be safe with third-generation nanoemulsion exhibiting higher cell internalization potential, reduced plasma drug concentration, and higher lung drug content.
Anti-LGI1 encephalitis

Objective: This nationwide study gives a detailed description of the clinical features and long-term outcome of anti–leucine-rich glioma-inactivated 1 (LGI1) encephalitis. Methods: We collected patients prospectively from October 2013, and retrospectively from samples sent to our laboratory from January 2007. LGI1 antibodies were confirmed with both cell-based assay and immunohistochemistry. Clinical information was obtained in interviews with patients and their relatives and from medical records. Initial MRI and follow-up MRI were revised blindly. Neuropsychological assessment was performed in those patients with follow-up over 2 years. Results: Annual incidence in the Netherlands was 0.83/million. A total of 34/38 patients had a limbic encephalitis. Subtle focal seizures (66%, autonomic or dyscognitive) and faciobrachial dystonic seizures (FBDS, 47%) mostly occurred before onset of memory disturbance. Later in the disease course, 63% had tonic-clonic seizures. Initial MRI showed hippocampal T2 hyperintensity in 74% of the patients. These lesions evolved regularly into mesial temporal sclerosis (44%). Substantial response to immunotherapy was seen in 80%, with early response of seizures and slow recovery of cognition. At follow-up ≥2 years, most surviving patients reported mild residual cognitive deficit with spatial disorientation. A total of 86% had persistent amnesia for the disease period. Relapses were common (35%) and presented up to 8 years after initial disease. Two-year case fatality rate was 19%. Conclusions: Anti-LGI1 encephalitis is a homogenous clinical syndrome, showing early FBDS and other focal seizures with subtle clinical manifestations, followed by memory disturbances. Better recognition will lead to earlier diagnosis, essential for prompt start of treatment. Long-term outcome of surviving patients is mostly favorable, but relapses are common.
Workload characterization of a leadership class storage cluster

Understanding workload characteristics is critical for optimizing and improving the performance of current systems and software, and architecting new storage systems based on observed workload patterns. In this paper, we characterize the scientific workloads of the world's fastest HPC (High Performance Computing) storage cluster, Spider, at the Oak Ridge Leadership Computing Facility (OLCF). Spider provides an aggregate bandwidth of over 240 GB/s with over 10 petabytes of RAID 6 formatted capacity. OLCFs flagship petascale simulation platform, Jaguar, and other large HPC clusters, in total over 250 thousands compute cores, depend on Spider for their I/O needs. We characterize the system utilization, the demands of reads and writes, idle time, and the distribution of read requests to write requests for the storage system observed over a period of 6 months. From this study we develop synthesized workloads and we show that the read and write I/O bandwidth usage as well as the inter-arrival time of requests can be modeled as a Pareto distribution.
Relevance of in vitro antimicrobial susceptibility of Brucella melitensis to relapse rate in human brucellosis

The in vitro susceptibility of Brucella melitensis was examined vis-a-vis the clinical outcome in 75 patients with brucellosis. The initial MICs for Brucella isolates from patients who relapsed and from those who did not were similar. Furthermore, the MICs for isolates from patients whose infections relapsed were no different from those for original isolates. Our results clearly showed that neither initial nor subsequent antibiotic susceptibility plays a role in the likelihood of relapse of patients with brucellosis.
The Evolution of the UNFCCC

This article takes stock of the evolution of the United Nations Framework Convention on Climate Change (UNFCCC) through the prism of three recent shifts: the move away from targeting industrial country emissions in a legally binding manner under the Kyoto Protocol to mandating voluntary contributions from all countries under the Paris Agreement; the shift from the top-down Kyoto architecture to the hybrid Paris outcome; and the broadening out from a mitigation focus under Kyoto to a triple goal comprising mitigation, adaptation, and finance under Paris. This review discusses the implications of these processes for the effectiveness, efficiency, and equity of the UNFCCC's institutional and operational settings for meeting the convention's objectives. It ends by sketching three potential scenarios facing the UNFCCC as it seeks to coordinate the Paris Agreement and its relationship to the wider landscape of global climate action.
Cardiotocographic Abnormalities Associated With Dinoprostone and Misoprostol Cervical Ripening

OBJECTIVE: To characterize the frequency and timing of cardiotocographic abnormalities associated with the use of 3 commercially available prostaglandin analogues, misoprostol, dinoprostone gel, and dinoprostone pessary, as labor preinduction agents. METHODS: One-hundred and eleven women undergoing induction of labor with an unfavorable cervix were randomized to receive either misoprostol 50 μg every 6 hours × 2 doses, dinoprostone gel 0.5 mg every 6 hours × 2 doses, or dinoprostone pessary 10 mg × 1 dose for 12 hours intravaginally. Oxytocin induction was initiated per standardized protocol. Cardiotocographic tracings were blindly reviewed, with abnormalities coded using established definitions. RESULTS: Fifty-five percent of women treated with misoprostol demonstrated an abnormal tracing event within the initial 24 hours of induction, compared with 21.1% with dinoprostone pessary and 31.4% with the dinoprostone gel. The mean (± standard deviation) number of abnormal events was significantly greater in women treated with misoprostol (5.0 ± 5.9) versus the dinoprostone pessary (1.6 ± 2.5) and gel (2.2 ± 3.1) (P < .05). In addition, these events occurred earlier after initial misoprostol dosing (5.0 ± 4.0 hours), compared with the dinoprostone pessary (9.4 ± 5.6 hours) and gel (7.7 ± 6.6). Thirty-nine percent of the misoprostol-treated women had abnormal patterns within 6 hours of initial dosing, compared with those treated with the dinoprostone pessary (7.9%) and gel (17.1%). CONCLUSION: Cardiotocographic abnormalities are more frequent after misoprostol administration compared with the dinoprostone analogues. The early onset and frequent nature of the tracing abnormalities associated with misoprostol raises concern for the potential use of misoprostol for outpatient cervical ripening. LEVEL OF EVIDENCE: II-1
Motivation, Usability and Their Interrelationships in a Self-paced Online Learning Environment

This study addressed how usability improvement and motivational design affect learners’ motivation and learning performance in a self-paced, online learning environment. The study also investigated the interrelationships between commonly-used usability measures and the motivation measures based on Keller’s ARCS model. A two-phase study approach was used. In Phase I, an existing self-paced, online safety training tutorial was used as the baseline. Two alternative designs were developed with improved usability and motivational design based on the ARCS model. In Phase II, the effects of the three interface designs were evaluated through a three-group, generalized randomized block covariate design experiment. A total of seventy-two college students (48 males and 24 females) participated in the usability testing and the online training session using one of the interface designs. Both quantitative and qualitative data were collected and analyzed. Results suggested a significant interface design effect on learner motivation. Learners who used the interface design with both usability improvement and motivational design applied (the UM group) showed the highest level of motivation. In particular, the attention level of the learners in the UM group was significantly higher than the baseline group. Results also indicated motivation differences between genders. Females showed higher scores than males in overall motivation score and in each of the four subscales of attention, relevance, confidence, and satisfaction. No significant difference in learning performance was found among the three treatment groups using different interface designs. None of the usability or motivation measures was a significant predictor of learning performance. Small to medium positive correlations were found between usability satisfaction and three motivation measures, i.e., attention, relevance and satisfaction. Content analysis identified a number of interface design components to be relevant to learners’ motivation components: overall appearance, graphics/multimedia, text appearance, page layout, navigation, and paging/scrolling. Implications and design recommendations for online tutorial interface design were discussed. Additional discussion was provided regarding the online learning environment and the integration of usability, motivation, and instructional design and technology.
Aortic Valve Replacement in Patients 80 Years and Older Operative Risks and Long‐term Results

BackgroundForty percent of 7.4 million Americans aged 80 years and older have symptomatic heart disease. Controversy exists as to whether the health care resources allotted to this patient subset represent a cost-effective approach to attaining a meaningful quality of life. Although aortic valve surgery carries greater risks in older than in younger patients, published studies reveal that the elderly should not be denied this procedure. Methods and ResultsTo determine the results of aortic valve replacement (AVR) in an elderly population, we retrospectively analyzed 171 consecutive patients aged 80 to 91 years (mean, 82.6 years; 86 men and 85 women) who underwent AVR at the Texas Heart Institute between 1975 and 1991. Seventy-seven patients had AVR only, and 94 patients had concomitant surgical procedures (coronary artery bypass graft surgery, 75 patients; mitral valve replacement, mitral valve repair, aneurysm repair, 19 patients). The overall 30-day early mortality was 17.5%. The early mortality was 5.2% for patients with AVR only and 27.7% for those with concomitant surgical procedures. Statistical analysis of 17 perioperative variables revealed that left ventricular ejection fraction of less than 45%, hypertension, congestive heart failure, angina, and concomitant surgical procedures were significant univariate predictors of early mortality. Multivariate analysis revealed that left ventricular ejection fraction of less than 45%, hypertension, and concomitant surgical procedures were independent predictors of operative mortality. Mean follow-up of survivors was 39 months. The overall actuarial survival at 1, 3, and 5 years was 90.8%, 84.2%, and 76.0%, respectively. ConclusionsThese results show that AVR can be performed with acceptable operative risks in the elderly. This study further shows that isolated AVR can be done with low operative mortality and that the performance of concomitant surgical procedures exposes elderiy patients to higher operative risks.
Sensitivity analysis in the optimal sizing of analog ICs by evolutionary algorithms

A multi-parameter sensitivity approach based on Richardson extrapolation, and applied to the optimal sizing of analog integrated circuits (ICs), is presented. First, the multiobjective evolutionary algorithm (EA) called non-dominated sorting genetic algorithm (NSGA-II), is applied to compute the feasible sizes of analog ICs, i.e. the optimal width and length (W/L) of every metal-oxide-semiconductor field-effect-transistor (MOSFET) is found. At this stage, the simulation program with integrated circuits emphasis (SPICE) is used to evaluate the electrical characteristics of analog ICs. Second, the multiparameter sensitivity analysis based on Richardson extrapolation, is applied to approximate the partial derivatives associated to the sensitivities on the performances of the ICs with respect to W/L of every MOSFET. The cases of study are three analog ICs, namely: voltage follower (VF), positive-type second generation current conveyor (CCII+), and current-feedback operational amplifier (CFOA). The proposed approach selects W/L feasible sizes presenting the lower sensitivities that are computed from the corresponding Pareto sets. Finally, 18 feasible (W/L sizes) solutions accomplishing 18 performance objectives and guaranteeing low W/L sensitivities for a complementary metal-oxide-semiconductor (CMOS) CFOA, are listed in Table I.
Complete Markets, Enforcement Constraints and Intermediation ∗

Alvarez and Jermann (2000) show that the constrained efficient allocations of endowment economies with complete markets and limited commitment can be decentralized with endogenous borrowing limits on the Arrow securities. In a model with capital accumulation, aggregate risk and competitive intermediaries, we show that such a decentralization is not possible unless one imposes an upper limit on the intermediaries' capital holdings. Since there is no empirical evidence of such restrictions, we also characterize the equilibrium with no capital accumulation constraints. We show that this allocation solves a similar system of equations to the one of the constrained optimal solution, a result which considerably simplifies the equilibrium computation. In addition, capital accumulation is higher in this case, since the intermediaries do not internalize that fact that a higher aggregate capital increases the incentives to default. Finally, this also implies that agents may enjoy a higher welfare in the long run in spite of the fact that this allocation is not constrained efficient
Non-centrosomal Microtubule Organization in Differentiated Cells 2

The centrosome consists of a pair of centrioles surrounded by pericentriolar material. During the formation of the mitotic spindle, multi-protein complexes in the pericentriolar material are involved in the nucleation and anchorage of microtubules. In postmitotic cells of many tissues, proteins of the pericentriolar material lose their association with the centrosome and redistribute to various sites in the cytoplasm, to the cellular cortex, or to the nuclear surface. Consequently, the organization of the microtubule network is changed. Localization of centrosomal proteins and organization of microtubules follow cell type-specific patterns, to fulfill specialized functions. For example, in polarized epithelia, microtubules are involved in transcytosis and establishment of epithelial polarity, in neurons microtubules are necessary for axonal transport, or in muscle microtubules participate in the assembly of sarcomeres and in the positioning of nuclei. In this review, the principles of microtubule organization in different cell types will be described. The role of microtubules in muscle cells and the potential involvement of microtubule-dependent processes in muscular diseases will be documented in detail. V. Dyachuk Centre de Biologie du Développement, Université Toulouse III, 118 route de Narbonne, 31062 Toulouse, France Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden C. Bierkamp • A. Merdes (*) Centre de Biologie du Développement, Université Toulouse III, 118 route de Narbonne, 31062 Toulouse, France e-mail: andreas.merdes@univ-tlse3.fr # Springer-Verlag Wien 2016 J. Lüders (ed.), The Microtubule Cytoskeleton, DOI 10.1007/978-3-7091-1903-7_2 27
A resistorless low current reference circuit for implantable devices

In this paper a basic, four-transistor, resistorless current reference circuit is described, aimed at implantable biomedical applications. The circuit takes advantage of two different thickness thermally grown gate oxides, which are available in most high voltage processes and in some of the latest sub-micron feature size processes. Current tuning is achieved by sizing the transistors accordingly.
High prevalence of Helicobacter pylori in saliva demonstrated by a novel PCR assay.

AIMS--To investigate the prevalence of Helicobacter pylori in the saliva of patients infected with this bacterium. METHODS--A novel polymerase chain reaction (PCR) assay was developed to detect H pylori in saliva and gastric biopsy specimens from patients undergoing endoscopy. RESULTS--Our PCR assay amplified a 417 base pair fragment of DNA from all 21 DNAs derived from H pylori clinical isolates but did not amplify DNA from 23 non-H pylori strains. Sixty three frozen gastric biopsy and 56 saliva specimens were tested. H pylori specific DNA was detected by PCR in all 39 culture positive biopsy specimens and was also identified from another seven biopsy specimens which were negative by culture but positive by histology. H pylori specific DNA was identified by PCR in saliva specimens from 30 (75%) of 40 patients with H pylori infection demonstrated by culture or histological examination, or both, and in three patients without H pylori infection in the stomach. CONCLUSION--The results indicate that the oral cavity harbours H pylori and may be the source of infection and transmission.
Validation of the International Classification of Functioning, Disability, and Health (ICF) Brief Core Set for osteoarthritis

Objective: To validate the International Classification of Functioning, Disability, and Health (ICF) Brief Core Set for osteoarthritis (OA) by comparing the preliminary Brief Core Set to a selection of categories from the Comprehensive Core Set that explain most of the variance of functioning and health. Methods: Patients with knee OA were asked to complete the Case Report Form for Patients, which includes the 36‐item Short Form Health Survey (SF‐36) and the Self‐administered Comorbidity Questionnaire (SCQ). For each patient, the research staff was asked to complete the Case Report Form for Health Professionals, which includes the ICF Comprehensive Core Set for OA. Two individual questions regarding patients' general health and functioning were completed by both the patients and the research staff. The ICF categories to be entered into an initial regression model were selected following systematic steps in accordance with the ICF structure. Based on the initial models, additional models were generated by systematically substituting the ICF categories included in the initial models with other highly intercorrelated categories. Results: A consecutive sample of 122 patients completed this study. Sixteen candidate ICF categories were identified by 15 linear regression models, which accounted for 5.5–57.7% of the total variance. Besides the two categories, b710 and b730, that are already included in the preliminary Brief Core Set, 14 additional categories were identified to be potential candidates for the Core Set. Conclusions: This study complemented the development of the Brief Core Set, which should be further refined by incorporating the opinions of patients, clinicians, and statisticians.
Evolution of the HIV-1 env Gene in the Rag2−/− γC−/− Humanized Mouse Model

ABSTRACT Rag2−/− γC−/− mice transplanted with human hematopoietic stem cells (DKO-hu-HSC mice) mimic aspects of human infection with human immunodeficiency virus type 1 (HIV-1), including sustained viral replication and CD4+ T-cell decline. However, the extent of HIV-1 evolution during long-term infection in these humanized mice, a key feature of the natural infection, has not been assessed fully. In this study, we examined the types of genotypic and phenotypic changes in the viral env gene that occur in the viral populations of DKO-hu-HSC mice infected with the CCR5-tropic isolate HIV-1JRCSF for up to 44 weeks. The mean rate of divergence of viral populations in mice was similar to that observed in a cohort of humans during a similar period of infection. Many amino acid substitutions were common across mice, including losses of N-linked glycosylation sites and substitutions in the CD4 binding site and in CD4-induced epitopes, indicating common selective pressures between mice. In addition, env variants evolved sensitivity to antibodies directed at V3, suggesting a more open conformation for Env. This phenotypic change was associated with increased CD4 binding efficiency and was attributed to specific amino acid substitutions. In one mouse, env variants emerged that exhibited a CXCR4-tropic phenotype. These sequences were compartmentalized in the mesenteric lymph node. In summary, viral populations in these mice exhibited dynamic behavior that included sequence evolution, compartmentalization, and the appearance of distinct phenotypic changes. Thus, humanized mice offer a useful model for studying evolutionary processes of HIV-1 in a complex host environment.