Miracle-dz/UniFAR-FTUs huggingface dataset:
Hematological adverse events in clozapine-treated children and adolescents.

OBJECTIVE To retrospectively examine rates of hematological adverse events (HAEs) in psychiatrically ill, hospitalized children treated with clozapine. METHOD Clozapine treatment was administered in an open-label fashion using a flexible titration schedule, and data from weekly complete blood counts was obtained. The rate of neutropenia and agranulocytosis (HAEs) development was determined for 172 eligible patients (mean age at clozapine initiation, 15.03 +/- 2.13 years) with a median observation period of 8 months. RESULTS Neutropenia (absolute neutrophil count <1,500/mm) developed in 23 (13%) patients and agranulocytosis (absolute neutrophil count <500/mm) in one (0.6%) patient. The cumulative probability of developing an initial HAE at 1 year of clozapine treatment was 16.1% (95% confidence interval 9.7%-22.5%). Eleven (48%) of 24 patients who developed an HAE were successfully rechallenged on clozapine. Eight (5%) of 172 patients from this sample eventually discontinued clozapine because of an HAE (one agranulocytosis, seven neutropenia). CONCLUSIONS The occurrence of HAEs is a significant risk associated with the administration of clozapine. However, in this sample, few children actually discontinued therapy because of an HAE and the incidence of agranulocytosis does not appear higher than what has been reported in the adult literature.
Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP‐25, and 5HT1B

It has been widely postulated that the categorical diagnosis of attention deficit hyperactivity disorder (ADHD) should be seen as the extreme end of a set of traits quantitatively distributed in the general population. A consequence of this is that the genes associated with DSM‐IV ADHD should also influence these underlying traits in non‐affected individuals. The aim of this study was to examine if specific candidate loci previously shown to be associated with DSM‐IV ADHD, also act as quantitative trait loci (QTLs) for ADHD‐symptoms in the general population. We have genotyped five candidate markers in a population‐based sample of male dizygous twin‐pairs (n = 329 pairs). We found little evidence to support a role for the previously‐nominated alleles of a DRD4 VNTR, a 5HT1B SNP, or a microsatellite marker near to DRD5, in the distribution of ADHD‐symptoms scores; however, we found some evidence to suggest that the DAT1 3′UTR VNTR and weak evidence that a microsatellite in SNAP‐25 may have a role in continuous measures of ADHD‐symptoms hyperactivity above and beyond their role in clinical ADHD. © 2004 Wiley‐Liss, Inc.
Phosphorylation of the tubulin‐binding protein, stathmin, by Cdk5 and MAP kinases in the brain

Regulation of cytoskeletal dynamics is essential to neuronal plasticity during development and adulthood. Dysregulation of these mechanisms may contribute to neuropsychiatric and neurodegenerative diseases. The neuronal protein kinase, cyclin‐dependent kinase 5 (Cdk5), is involved in multiple aspects of neuronal function, including regulation of cytoskeleton. A neuroproteomic search identified the tubulin‐binding protein, stathmin, as a novel Cdk5 substrate. Stathmin was phosphorylated by Cdk5 in vitro at Ser25 and Ser38, previously identified as mitogen‐activated protein kinase (MAPK) and p38 MAPKδ sites. Cdk5 predominantly phosphorylated Ser38, while MAPK and p38 MAPKδ predominantly phosphorylated Ser25. Stathmin was phosphorylated at both sites in mouse brain, with higher levels in cortex and striatum. Cdk5 knockout mice exhibited decreased phospho‐Ser38 levels. During development, phospho‐Ser25 and ‐Ser38 levels peaked at post‐natal day 7, followed by reduction in total stathmin. Inhibition of protein phosphatases in striatal slices caused an increase in phospho‐Ser25 and a decrease in total stathmin. Interestingly, the prefrontal cortex of schizophrenic patients had increased phospho‐Ser25 levels. In contrast, total and phospho‐Ser25 stoichiometries were decreased in the hippocampus of Alzheimer's patients. Thus, microtubule regulatory mechanisms involving the phosphorylation of stathmin may contribute to developmental synaptic pruning and structural plasticity, and may be involved in neuropsychiatric and neurodegenerative disorders.
Prehospital Mass-Casualty Triage Training—Written Versus Moulage Scenarios: How Much Do EMS Providers Retain?

Abstract Introduction The aim of this study was to assess the effectiveness of written and moulage scenarios using video instruction for mass-casualty triage by evaluating skill retention at six months post intervention. Methods Prehospital personnel were instructed in the START method of mass-casualty triage using a video. Moulage and written testing were completed by each participant immediately after instruction and at six months post instruction. Results There was a significant decrease in performance between initial and six-month testing, indicating skill decay and loss of retention of triage skills after an extended nonuse period. There were no statistically significant differences between written and moulage testing results at either initial testing or at six months. Prior skill level did not influence test performance on the type of testing conducted or long-term retention of triage skills. Conclusion These data confirm the skill deterioration associated with an infrequently used triage method. Further research to more precisely define triage criteria, as well as the ability to apply the criteria in a clinical setting and to rapidly identify patients at risk for morbidity/mortality is needed. RisaviBL, TerrellMA, LeeW, HolstenDLJr. Prehospital mass-casualty triage training—written versus moulage scenarios: how much do EMS providers retain? Prehosp Disaster Med. 2013;28(3):1-6.
Social contexts, age and juvenile delinquency: a community perspective

Objective — Social disorganisation of communities, family bonds, school bonds, the peer group and age, have been shown to be related (either positively or negatively) to delinquency. This study addressed gaps in the literature by (1) using a large and randomly drawn sample of adolescents, within a large number of randomly selected communities; (2) investigating the influence of community social disorganisation directly on delinquency, while including in the same model the moderating effect of community social disorganisation on the micro-contexts of family, school, and peer group, as well as the direct effects of these micro-contexts; and (3) including age as a variable likely to have both direct effects on delinquency and moderating effects on the micro- and macro-level social contexts. Method — The public-use data set of Wave I of the (US) National Longitudinal Study of Adolescent Health was used. The model was tested using hierarchical linear modelling and included the social disorganisation of communities; adolescents' bonds to school and family, family controls and involvement with a deviant peer group; and age and its interaction with these social contexts. Results — Community social disorganisation was found to be positively related to delinquency, but effects of micro-level contexts were not found to be moderated by social disorganisation. Family bonds and controls, and school bonds, were negatively related to delinquency. No effect of peer group was found. Age was found to have a direct effect; effects of the interaction of age with family controls and age with school bonds were also significant. Conclusions — Results strengthen those from previous studies (using more limited samples) which show that integrated views of macro- and micro-level social contexts and developmental trends are necessary to understand delinquency.
Fine mapping of an IgE-controlling gene on chromosome 2q: Analysis of CTLA4 and CD28.

BACKGROUND Several genomic regions have been identified that might contain genes contributing to the development of asthma and atopy. These include chromosome 2q33, where we have observed evidence for linkage for variation in total serum IgE levels in a Dutch asthma population. Two candidate genes, CTLA4 and CD28, important homeostatic regulators of T-cell activation and subsequent IgE production, map within this candidate region. OBJECTIVE We sought to fine-map the chromosome 2q33 region and evaluate CTLA4 and CD28 as candidate genes for the regulation of total serum IgE levels and related phenotypes. METHODS The coding regions of CTLA4 and CD28 were resequenced in 96 individuals; 4 novel SNPs in CTLA4 and 10 in CD28 were identified. Polymorphisms in both genes were analyzed in 200 asthmatic probands and their spouses (n = 201). RESULTS Subsequent fine- mapping in this region has resulted in an increased log of the odds (lod) score (1.96 to 3.16) for total serum IgE levels. For CTLA4, the +49 A/G single nucleotide polymorphism (SNP) in exon 1 and the 3 ' untranslated region microsatellite were significantly associated with total serum IgE levels (P =.0005 and.006, respectively). For the combined +49 A/G and 3 'untranslated region genotypes, individuals homozygous for the risk allele for both polymorphisms (AA and 86/86) had the highest total serum IgE values (87.1 IU/mL), whereas those individuals with the GG and XX/XX genotypes (anything but the 86-bp allele) had the lowest IgE values (29.3 IU/mL). Significant association was also observed for the CTLA4 -1147 C/T SNP with bronchial hyperresponsiveness (BHR) and asthma (P =.008 and.012, respectively), but not for allergy-related phenotypes. Promoter luciferase assays examining the -1147 polymorphism suggested that the T allele, which was associated with increased BHR susceptibility, was expressed at half the level of the C allele. Individuals with the risk genotypes for both BHR (-1147 CT or TT) and elevated IgE levels (+49 AA) were 4.5 times more likely to have asthma than individuals with both nonrisk genotypes (P =.0009). No significant associations were observed for SNPs in CD28. CONCLUSION These data suggest that the costimulatory pathway, specifically CTLA4, is important in the development of atopy and asthma.
FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Using life cycle assessment to support the development of electrified road vehicles

The anthropogenic pressure on the Earth system already overshoots safe limits for climate change, so there is an urgent need to drastically reduce greenhouse gas emissions caused by transportation. Electric propulsion technology is a promising solution that can decouple fossil fuel use from road vehicle traffic. Additional benefits include removed tailpipe exhaust gas emissions, which currently damage human health and the environment, both locally and regionally. However, electrification of vehicles could lead to problem shifts, e.g. from the use of fossil fuels to the generation of fossil electricity. Even when combined with renewable energy, there are trade-offs between benefits in operation and added environmental load during manufacturing, shifting from airborne emissions to resource related impacts. This is because electric powertrain components require new materials and more advanced processing compared to conventional vehicle parts. The environmental impacts of vehicle electrification can be analyzed using life cycle assessment (LCA). This is a holistic systems tool, where all life cycle stages, from raw material acquisition to disposal, are investigated for potential contribution to environmental problems. For LCA of vehicles, a well-to-wheels study examines the life cycle of the energy carrier, i.e. a fuel or electricity, whereas complete LCA includes the production, use and disposal of the vehicle as such. A thorough review of the research field exposed short-comings in both methodology and inventory data. This thesis aims to discuss in what ways LCA support the development of electrified road vehicles, and present contributions on how the methodology can advance to provide better support, with the goal to minimize environmental impact of vehicles in the long term. Two component data models were developed. These estimate the mass and composition of one electrical traction motor and one inverter unit (the motor controller), calculate full gate-to-gate manufacturing inventories, and point to an existing database to establish cradle-to-gate models. Both are scalable from basic engineering parameters, build on typical design solutions and are easy-to-use. During this work, 45 new unit process datasets for manufacturing were compiled and the thesis discusses and presents useful strategies for data collection.
A program to prepare minority students for careers in medicine, science, and other high‐level professions

&NA; The Gateway to Higher Education program is a comprehensive four‐year high school program with specially designed enrichments and supports. Its principal goal is to increase the number of minority students who will be prepared to enter training for high‐level professional careers, especially in medicine and science. The program was established in September 1986 to demonstrate that minority students who perform at least at grade level can begin a rigorous curriculum in the ninth grade and achieve outstanding results, provided that the necessary support systems are in place. For 1990–91, 750 students are enrolled in Gateway programs at five New York City public high schools, and the first 119 students graduated in June 1990. The graduates have demonstrated significant achievement compared with that of their peers, as measured by standardized tests and the graduates' participation in research mentorships and college acceptances. In order to expand on its initial success, the program has increased its scope of activity to include over 400 students at the junior high school level.
Carrierless design for handling and processing of ultrathin wafers

A common requirement for all current and future TSV (Through Silicon Via) applications is the ability to handle and process thinned Silicon Wafers, usually in the range of 150μm or much below. Silicon Wafers of this thickness cannot be handled without support as wafers with the standard thickness. One solution to tackle this problem is the use of wafer-support-systems (WSS), in which the thinned wafers are bonded temporarily to a carrier wafer, which gives the wafer mechanical stability. Another solution for handling are carrierless systems, in which the wafer is modified in a way that it is thin and mechanically rigid at the same time. Existing carrierless systems provide mechanical integrity for the wafer, but lack the full integration into backside processing. In this paper, we present a carrierless approach that provides mechanical stability and can be integrated into backside processing technology at the same time. We present results of a carrierless wafer with a thickness of 60μm only which has undergone a bumping process at the backside.
Heart Rate Variability, Left Ventricular Functions, and Cardiac Autonomic Neuropathy in Patients Undergoing Chronic Hemodialysis

Objective. Autonomic neuropathy and impairment of left ventricular functions (LVF) have been frequently encountered in chronic renal failure (CRF). The aim of the present study was to evaluate the relationship of cardiac autonomic modulation impairments, as assessed by means of heart rate variability (HRV), with clinical characteristics, and left ventricular function in the patients with CRF undergoing hemodialysis (HD). Methods. Twenty control subjects (Group I) and 22 comparable by age and gender patients with CRF undergoing hemodialysis (Group II) were enrolled in the study. After routine clinical and biochemical evaluations, electrocardiography, and 2 Dimensional, M Mode echocardiography were performed in all participants. Frequency domain HRV analysis was studied by using Kardiosis System. The powers (P1 and P2) and the central frequencies (F1 and F2) of low and of high frequency spectral bands were recorded. Results. End systolic (ESV) and end diastolic volumes (EDV) were significantly higher in Group II (59.3 ± 21.1 mL vs. 34.0 ± 14.3 mL and 131.5 ± 37.3 mL vs. 96.9 ± 18.9 mL, p<0.01, p<0.05, respectively) when compared to those of Group I. Ejection fraction (EF) and fractional shortening (FS) were significantly lower in Group II than in control subjects (52.3 ± 2.4% vs. 63.7 ± 10.1% and 0.29 ± 0.01 vs. 0.34 ± 0.07, p<0.001, p<0.05, respectively). P1 and P2 were decreased in Group II than in Group I (136.2 ± 173.9 m s2 vs. 911.0 ± 685.5 and 96.5 ± 149.6 vs. 499.7 ± 679.5, p<0.001, p<0.01, respectively). Significant correlations were found between high frequency spectral power and dialysis duration (DD), ESV, EDV, EF, FS (r = 0.52 p<0.01, r = 0.68 p<0.001, r = 0.65 p<0.002, r = 0.66 p<0.02, and r = 0.69 p<0.01). Conclusion. As a result, the dependence of cardiac autonomic neuropathy on the disease duration and degree of left ventricular function impairment was shown in the patients undergoing chronic hemodialysis.
Functional connectivity of the prefrontal cortex in Huntington’s disease

Background: Huntington’s disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. Aim: To assess the functional connectivity between prefrontal brain regions in patients with Huntington’s disease, compared with normal controls, using functional magnetic resonance imaging. Patients and methods: 20 patients with Huntington’s disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington’s disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex. Results: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington’s disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington’s disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington’s disease between the left anterior cingulate and prefrontal regions. Conclusions: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington’s disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington’s disease. It is speculated whether significantly greater levels of activation in patients with Huntington’s disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.
Genes involved in brassinosteroids's metabolism and signal transduction pathways

Brassinoesteroides sao esteroides vegetais, essenciais para o crescimento e o desenvolvimento, que apresentam um oxigenio no carbono C-3 e oxigenios adicionais em um ou mais dos atomos de carbono C-2, C-6, C-22 e C-23. Nos ultimos anos, a aplicacao de tecnicas de genetica molecular possibilitou progresso significativo no entendimento da regulacao da via biossintetica e na identificacao de varios componentes da via de transducao de sinal de brassinoesteroides. Buscas em bases de dados eletronicas mostram duzias de registros para genes relacionados a brassinoesteroides nos ultimos doze meses, demonstrando os grandes esforcos desenvolvidos neste campo. Esta revisao destaca os recentes avancos na caracterizacao de genes e mutacoes que estao auxiliando na elucidacao dos mecanismos moleculares envolvidos na sintese/metabolismo, e percepcao e resposta de brassinoesteroides, com enfase especial no seu papel no alongamento de celulas vegetais. Aspectos do envolvimento de BRs na regulacao de proteinas que controlam o ciclo cellular tambem sao discutidos.
Characterization of B-cell epitopes in the envelope glycoproteins of simian immunodeficiency virus.

We identified previously a neutralizing epitope in the V2 domain of the simian immunodeficiency virus (SIVmac) external envelope protein. The present study reports identification of five additional linear epitopes of SIVmac (isolate 251) by immunological screening of a peptide library expressed in yeast, using SIVmac-infected macaque sera. Three epitopes were localized in the envelope glycoproteins and the two others in the reverse transcriptase and in the Rev regulatory protein. Antibody response against the four envelope epitopes was monitored for 2 years in 12 macaques experimentally infected by SIVmac251. These four envelope regions represent major immunodominant epitopes of the SIVmac. Two epitopes are located in the V3 domain (a.a. 311-330) of the external gp130 and near the amino terminal part (a.a. 601-619) of the transmembrane gp36, in regions similar to those identified in HIVs, demonstrating immunological similarities between the envelopes of SIVs and HIVs. SIV-specific immunodominant epitopes were also identified in the V1 (a.a. 111-130) and V2 (a.a. 171-190) domains of the external gp130. In particular, antibody response against the V2 neutralizing region seems to play some role in the control of disease progression in SIVmac-infected macaques.
Distribution and density of medium- and short-wavelength selective cones in the domestic pig retina.

The topography of medium (M)- and short (S)-wavelength sensitive cone photoreceptors was studied in the domestic pig retina. Antisera specific for M or S opsin as well as cone photoreceptor proteins arrestin and alpha-transducin were used to label cone types. Retinal wholemounts and their blood vessel patterns were drawn and specific regions removed. The wholemounts were immunocytochemically labelled to detect both M and S cones, and the specific regions labelled to detect S cones. Cones were counted in a 1 mm grid pattern, using the drawings as a guide. Pig retina has a high cone density retinal streak extending across the retina covering the optic disc (OD) and horizontal meridian. Densities in the streak are 20,000-35,000 mm(-2). Two higher peaks occur in the streak, one in temporal retina near the OD (39,000 mm(-2)) and the other in nasal retina 5-7 mm from the OD (40,500 mm(-2)). The lowest cone density is in far peripheral inferior retina (7000 mm(-2)). The total number of cones in pig retina is 17-20 million. Both types of cones are found throughout the retina, with S cone percentages ranging from 7.4 to 17.5% in no consistent topographical pattern. S cones have an irregular local distribution which can vary from a regular hexagonal pattern to small clusters of adjacent S cones to small areas lacking S cones. Double-label immunocytochemistry found that virtually all S cone outer segments (OS) contain some M opsin. M cone OS do not label at detectible levels for S opsin. Domestic pig retina is widely available, large, has a high cone density and has two types of cones. This tissue should be an excellent source for biochemical analysis of cone proteins, and for in vitro approaches to understanding cone survival factors.
Are Macroeconomic Density Forecasts Informative ? April 2016

We consider whether survey density forecasts (such as the inflation and output growth histograms of the US Survey of Professional Forecasters) are superior to unconditional density forecasts. The unconditional forecasts assume that the average level of uncertainty experienced in the past will prevail in the future, whereas the SPF projections ought to be adapted to current conditions and the outlook at each forecast origin. The SPF forecasts might be expected to outperform the unconditional densities at the shortest horizons, but this does not transpire to be the case, for either the aggregate or individual respondents’forecasts.