Miracle-dz/UniFAR-FTUs huggingface dataset:
Pneumococcal Meningitis: Development of a New Animal Model

Hypothesis: The rat is a suitable animal to establish a model for the study of pneumococcal meningitis postcochlear implantation. Background: There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis postimplantation and are based on relatively small animal numbers, making it difficult to assess the cause-and-effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant. Methods: Eighteen nonimplanted rats were infected with 1 × 106 and 1 × 108 colony-forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear, and i.p.) to examine for evidence of meningitis during 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 × 1010 CFU i.p., 3 × 108 CFU middle ear, and 1 × 106 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. The histological pattern of cochlear infections for each of the three different inoculating routes were examined. Results: Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system via either the cochlear aqueduct or canaliculi perforantes of the osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent, and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 nonimplanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours postinoculation. Conclusion: Meningitis in implanted rats after inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 nonimplanted rats suggests that longer postinoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work, we have developed a new animal model that will allow quantitative risk assessment of meningitis postcochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies.
Physical development of young talented tennis players

Na medida em que todas as obras da UC Digitalis se encontram protegidas pelo Código do Direito de Autor e Direitos Conexos e demais legislação aplicável, toda a cópia, parcial ou total, deste documento, nos casos em que é legalmente admitida, deverá conter ou fazer-se acompanhar por este aviso. Physical development of young talented tennis players Autor(es): Kramer, Tamara; Huijgen, Barbara; Elferink-Gemser, Marije T; Lyons, Jim; Visscher, Chris Publicado por: Imprensa da Universidade de Coimbra URL persistente: URI:http://hdl.handle. net/10316.2/31704 DOI: DOI:http://dx.doi. org/10.14195/978-989-26-0506-7_7
Physicians’ Anxiety Due to Uncertainty and Use of Race in Medical Decision Making

Background:The explicit use of race in medical decision making is contested. Researchers have hypothesized that physicians use race in care when they are uncertain. Objectives:The aim of this study was to investigate whether physician anxiety due to uncertainty (ADU) is associated with a higher propensity to use race in medical decision making. Research Design:This study included a national cross-sectional survey of general internists. Subjects:A national sample of 1738 clinically active general internists drawn from the SK&A physician database were included in the study. Measures:ADU is a 5-item measure of emotional reactions to clinical uncertainty. Bonham and Sellers Racial Attributes in Clinical Evaluation (RACE) scale includes 7 items that measure self-reported use of race in medical decision making. We used bivariate regression to test for associations between physician characteristics, ADU, and RACE. Multivariate linear regression was performed to test for associations between ADU and RACE while adjusting for potential confounders. Results:The mean score on ADU was 19.9 (SD=5.6). Mean score on RACE was 13.5 (SD=5.6). After adjusting for physician demographics, physicians with higher levels of ADU scored higher on RACE (+&bgr;=0.08 in RACE, P=0.04, for each 1-point increase in ADU), as did physicians who understood “race” to mean biological or genetic ancestral, rather than sociocultural, group. Physicians who graduated from a US medical school, completed fellowship, and had more white patients scored lower on RACE. Conclusions:This study demonstrates positive associations between physicians’ ADU, meanings attributed to race, and self-reported use of race in medical decision making. Future research should examine the potential impact of these associations on patient outcomes and health care disparities.
Mycophenolic Acid Differentially Impacts B Cell Function Depending on the Stage of Differentiation

Production of pathogenic Abs contributes to disease progression in many autoimmune disorders. The immunosuppressant agent mycophenolic acid (MPA) has shown clinical efficacy for patients with autoimmunity. The goal of these studies was to elucidate the mechanisms of action of MPA on B cells isolated from healthy individuals and autoimmune patients. In this study, we show that MPA significantly inhibited both proliferation and differentiation of primary human B cells stimulated under various conditions. Importantly, MPA did not globally suppress B cell responsiveness or simply induce cell death, but rather selectively inhibited early activation events and arrested cells in the G0/G1 phase of the cell cycle. Furthermore, MPA blocked expansion of both naive and memory B cells and prevented plasma cell (PC) differentiation and Ab production from healthy controls and individuals with rheumatoid arthritis. Finally, whereas MPA potently suppressed Ig secretion from activated primary B cells, terminally differentiated PCs were not susceptible to inhibition by MPA. The target of MPA, IMPDH2, was found to be downregulated in PCs, likely explaining the resistance of these cells to MPA. These results suggest that MPA provides benefit in settings of autoimmunity by directly preventing activation and PC differentiation of B cells; however, MPA is unlikely to impact autoantibody production by preexisting, long-lived PCs.
Seismic Imaging of the Far Hemisphere of the Sun

We apply phase-sensitive helioseismic holography to Solar and Heliospheric Observatory/Michelson Dopper Imager data to demonstrate how acoustic travel-time perturbations may be mapped over the entire portion of the Sun facing away from the Earth, including the polar regions. In addition to offering significant improvements to ongoing space weather forecasting efforts, the procedure offers the possibility of local seismic monitoring of both the temporal and spatial variations in the acoustic properties of the Sun over all of the far surface.
Psychometric study of the Rational Experiential Inventory among undergraduate Argentinean students

The Rational Experiential Inventory consist of two large scales (rational and experiential), each one with two subscales (ability and engagement). Their psychometric properties have been studied in several countries, but there are no reports in the Latin American context. In this study we analyzed the factor structure and internal consistency of the Rational Experiential Inventory, and assessed the relationships between processing styles and different personality dimensions in a sample of students from Argentina. The results show an underlying twofactor structure with good internal consistency values. Only one significant relationship between experiential style and extraversion was observed. A version with fewer items was attained and, due to its adequate psychometric properties, this instrument may be used in future research studies.
Enhancing Community Interactions with Data-Driven Chatbots--The DBpedia Chatbot

In this demo, we introduce the DBpedia chatbot, a knowledge-graph-driven chatbot designed to optimize community interaction. The bot was designed for integration into community software to facilitate the answering of recurrent questions. Four main challenges were addressed when building the chatbot, namely (1) understanding user queries, (2) fetching relevant information based on the queries, (3) tailoring the responses based on the standards of each output platform (i.e. Web, Slack, Facebook) as well as (4) developing subsequent user interactions with the DBpedia chatbot. With this demo, we will showcase our solutions to these four challenges.
Practice of Epidemiology Comparison of Random Forest and Parametric Imputation Models for Imputing Missing Data Using MICE: A CALIBER Study

Multivariate imputation by chained equations (MICE) is commonly used for imputing missing data in epidemiologic research. The “ true ” imputation model may contain nonlinearities which are not included in default imputation models. Random forest imputation is a machine learning technique which can accommodate nonlinearities and interactions and does not require a particular regression model to be specified. We compared parametric MICE with a random forest-based MICE algorithm in 2 simulation studies. The first study used 1,000 random samples of 2,000 persons drawn from the 10,128 stable angina patients in the CALIBER database (Cardiovascular Disease Research using Linked Bespoke Studies and Electronic Records; 2001 – 2010) with complete data on all covariates. Variables were artificially made “ missing at random, ” and the bias and efficiency of parameter estimates obtained using different imputation methods were compared. Both MICE methods produced unbiased estimates of (log) hazard ratios, but random forest was more efficient and produced narrower confidence intervals. The second study used simulated data in which the partiallyobserved variable depended on the fully observed variables in a nonlinear way. Parameter estimates were less biased using random forest MICE, and confidence interval coverage was better. This suggests that random forest imputation may be useful for imputing complex epidemiologic data sets in which some patients have missing data.
On the Structure and Dynamics of Indian Monsoon Depressions

AbstractERA-Interim reanalysis data from the past 35 years have been used with a newly developed feature tracking algorithm to identify Indian monsoon depressions originating in or near the Bay of Bengal. These were then rotated, centralized, and combined to give a fully three-dimensional 106-depression composite structure—a considerably larger sample than any previous detailed study on monsoon depressions and their structure. Many known features of depression structure are confirmed, particularly the existence of a maximum to the southwest of the center in rainfall and other fields and a westward axial tilt in others. Additionally, the depressions are found to have significant asymmetry owing to the presence of the Himalayas, a bimodal midtropospheric potential vorticity core, a separation into thermally cold (~−1.5 K) and neutral (~0 K) cores near the surface with distinct properties, and the center has very large CAPE and very small CIN. Variability as a function of background state has also been explo.
Activation of Meningeal Nociceptors by Cortical Spreading Depression: Implications for Migraine with Aura

Attacks of migraine with aura represent a phenomenon in which abnormal neuronal activity in the cortex produces sensory disturbances (aura) some 20–40 min before the onset of headache. The purpose of this study was to determine whether cortical spreading depression (CSD)—an event believed to underlie visual aura—can give rise to activation of nociceptors that innervate the meninges—an event believed to set off migraine headache. CSD was induced in anesthetized male rats by stimulation of the visual cortex with electrical pulses, pin prick, or KCl; single-unit activity of meningeal nociceptors was monitored in vivo in the rat before and after CSD. Regardless of the method of cortical stimulation, induction of CSD was recorded in 64 trials. In 31 of those trials, CSD induced a twofold increase in meningeal nociceptor firing rate that persisted for 37.0 ± 4.6 min in trials in which activity returned to baseline, or >68 min in trials in which activity remained heightened at the time recording was interrupted. In two-thirds of the trials, onset of long-lasting neuronal activation began ∼14 min after the wave of CSD. The findings demonstrates for the first time that induction of CSD by focal stimulation of the rat visual cortex can lead to long-lasting activation of nociceptors that innervate the meninges. We suggest that migraine with aura is initiated by waves of CSD that lead up to delayed activation of the trigeminovascular pathway.
Examining the case for functional behavior assessment as an evidence-based practice for students with emotional and behavioral disorders in general education classrooms

ABSTRACT This article is a review of functional behavior assessment studies in general education setting for students with emotional and behavioral disorders. The studies were assessed in accordance with published standards for evidence-based practices. Overall, few studies met criteria for inclusion in this review and even fewer studies included all three parts of a complete FBA. Results indicate that there are few studies of FBA that specifically address students with behavior problems in general education. Although FBA may have future promise for the described setting and population, there currently is too little information available and lack of consistency in practice to yet claim it is an evidence-based practice.
Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) inhibitors

Inhibitors of topoisomerase I (Top1) that result in stalled Top1 cleavage complexes (Top1cc) are commonly employed against cancer. Combination chemotherapy with DNA repair inhibitors can potentially improve response to these widely used chemotherapeutics. One line of inquiry focuses on inhibitors of tyrosyl-DNA phosphodiesterase 1 (Tdp1), a repair enzyme for Top1cc. Tdp1 catalyzes the hydrolysis of DNA adducts covalently linked to the 3'-phosphate of DNA, including Top1-derived peptides and also 3'-phosphoglycolates. Tdp1 inhibitors should synergize not only with Top1-targeting drugs (camptothecins, indenoisoquinolines), but also with bleomycin, topoisomerase II (Top2) inhibitors (etoposide, doxorubicin) and DNA alkylating agents. Here, we summarize the structure–activity relationship obtained from the reported Tdp1 inhibitors. Better understanding of Top1cc repair in vivo coupled with detailed structural studies on Tdp1–inhibitor interaction will be crucial in guiding the rational design of Tdp1 inhibitors.
Gender Di erences in Sickness Absence and Family Responsibility ∗

Swedish women are on average more absent from work for health reasons while simultaneously having lower mortality rates. This con icting pattern suggests that part of the gender gap in health-related absenteeism stems from di erences between genders not related to actual health. One possible explanation could be that women, because of relatively more risk-averse behavior, utilize absence from work as a preventative measure to a higher degree than men, which e ectively prolongs their relative life expectancy. Another reason, put forward by Paringer (1983), is that, due to traditional gender norms, households optimize by having a lower health threshhold of work absence for the wife than for the husband. We test these hypotheses using detailed Swedish register data on sickness absence, in-hospital care and mortality. We nd that men and women's preventive health behaviors di er as women on average have more sickness absence than men given health. However, these di erent health thresholds of work absence are not driven by increased health investments from home production responsibilities. ∗ †Department of Economics, Uppsala University, UCLS and IFAU, daniel.avdic@ifau.uu. se ‡Department of Economics, Uppsala University, UCLS, IFAU and IZA, per.johansson@ifau.uu. se 1
Ghrelin concentrations in Prader–Willi syndrome (PWS) infants and children: changes during development

Background Prader–Willi syndrome (PWS) is associated with failure to thrive in infancy and progressive hyperphagia and obesity in childhood. This progressive weight gain is associated with hyperghrelinaemia and increased insulin sensitivity. The role of ghrelin excess in the pathogenesis of obesity is unclear.
Adolescent cancer: coping with treatment-related pain.

Abstract A small convenience sample of adolescents undergoing cancer treatments was queried about what they did to deal with treatment-related pain. They frequently reported using action and affective strategies. Action strategies included mental redefinition of the experience, self-distraction, self-talk, and selective ignoring. Affective strategies inlcuded crying and resigned acceptance of the situation. Approximately 70% of the adolescents reported wanting parents present during procedures. The adolescents also indicated that the worst part about having cancer was the repeated exposure to cancer treatments.
Left Dorsomedial Frontal Brain Damage Is Associated with Insomnia

Insomnia is a common sleep disorder, yet its pathophysiological basis remains poorly understood. Studying a group of 192 patients with focal brain lesions, we show a significant association between insomnia and left dorsomedial prefrontal damage. Our findings are the first to demonstrate a link between insomnia and a discrete locus of brain damage, providing novel insight into the neurobiological mechanisms of sleep maintenance.
One-Carbon Metabolism Biomarkers and Risk of Colon and Rectal Cancers

Background: Folate intake has been associated with reduced colorectal cancer risk; however, few studies have prospectively examined circulating folate or other related one-carbon biomarkers. Methods: We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 50- to 69-year-old Finnish men to investigate associations between serum folate, vitamin B6, vitamin B12, riboflavin, and homocysteine and risk of colon and rectal cancers. Controls were alive and cancer-free at the time of case diagnosis and matched 1:1 on age and date of baseline fasting serum collection with cases (152 colon and 126 rectal cancers). Multivariate-adjusted odds ratios and 95% confidence intervals were calculated using conditional logistic regression. Results: Serum vitamin B6 was inversely associated with colon cancer [odds ratio, 0.30 (95% confidence interval, 0.11-0.82) in the highest versus lowest quintile]. An increased risk of colon cancer was suggested for men in the middle quintile of serum folate, but without indication of a dose-response relationship. None of the other serum biomarkers were associated with colon or rectal cancer, and we observed no interactions with alcohol consumption or methionine or protein intake. A priori combinations of the five one-carbon serum biomarkers provided no clear evidence to support a collective influence on colorectal cancer risk. Conclusions: Our results support the hypothesis that higher vitamin B6 status may play a role in inhibiting colon cancer carcinogenesis; however, folate and other one-carbon related biomarkers were not associated with colon or rectal cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3233–40)
The arcuate nucleus and neuropeptide Y contribute to the antitumorigenic effect of calorie restriction

Calorie restriction (CR) is known to have profound effects on tumor incidence. A typical consequence of CR is hunger, and we hypothesized that the neuroendocrine response to CR might in part mediate CR’s antitumor effects. We tested CR under appetite suppression using two models: neuropeptide Y (NPY) knockout mice and monosodium glutamate‐injected mice. While CR was protective in control mice challenged with a two‐stage skin carcinogenesis model, papilloma development was neither delayed nor reduced by CR in the monosodium glutamate‐treated and NPY knockout mice. Adiponectin levels were also not increased by CR in the appetite‐suppressed mice. We propose that some of CR’s beneficial effects cannot be separated from those imposed on appetite, and that NPY neurons in the arcuate nucleus of the hypothalamus are involved in the translation of reduced intake to downstream physiological and functional benefits.
The inflammasome and lupus: another innate immune mechanism contributing to disease pathogenesis?

Purpose of reviewThe role of innate immunity in systemic lupus erythematosus (SLE) has been a rapidly expanding area of research over the last decade. Included in this rubric is the concept that activation of the inflammasome, a molecular complex that activates caspase-1 and in turn the cytokines IL-1&bgr; and IL-18, is important in lupus pathogenesis. This review will summarize the recent discoveries exploring the role of the inflammasome machinery in SLE. Recent findingsImmune complexes can activate the NLRP3 inflammasome, and SLE-derived macrophages are hyper-responsive to innate immune stimuli, leading to enhanced activation of the inflammasome and production of inflammatory cytokines. Work in several murine models suggests an important role for the NLRP3 inflammasome in mediating lupus nephritis. Caspase-1, the central enzyme of the inflammasome, is essential for the development of type I interferon responses, autoantibody production, and nephritis in the pristane model of lupus. The absence of melanoma 2 inflammasome may have protective and pathogenic roles in SLE. SummaryRecent evidence suggests that the inflammasome machinery is dysregulated in SLE, plays an important role in promotion of organ damage, and may mediate cross-talk between environmental triggers and the development of lupus. Further research should focus on whether inhibition of inflammasome components may serve as a viable target for therapeutic development in SLE.
Nano-Cathodoluminescence Measurement of Asymmetric Carrier Trapping and Radiative Recombination in GaN and InGaN Quantum Disks

Abstract The ability to characterize recombination and carrier trapping processes in group-III nitride-based nanowires is vital to further improvements in their overall efficiencies. While advances in scanning transmission electron microscope (STEM)-based cathodoluminescence (CL) have offered some insight into nanowire behavior, inconsistencies in nanowire emission along with CL detector limitations have resulted in the incomplete understanding in nanowire emission processes. Here, two nanowire heterostructures were explored with STEM-CL: a polarization-graded AlGaN nanowire light-emitting diode (LED) with a GaN quantum disk and a polarization-graded AlGaN nanowire with three different InGaN quantum disks. Most nanowires explored in this study did not emit. For the wires that did emit in both structures, they exhibited asymmetrical emission consistent with the polarization-induced electric fields in the barrier regions of the nano-LEDs. In the AlGaN/InGaN sample, two of the quantum disks exhibited no emission potentially due to the three-dimensional landscape of the sample or due to limitations in the CL detection.