161 research outputs found

    Modulation of internal model formation during force field-induced motor learning by anodal transcranial direct current stimulation of primary motor cortex

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    Human subjects can quickly adapt and maintain performance of arm reaching when experiencing novel physical environments such as robot-induced velocity-dependent forcefields.Using anodal transcranial direct current stimulation (tDCS) this study showed that the primary motor cortex may play a role in motor adaptation of this sort. Subjects performed arm reaching movement trials in three phases: in a null force field (baseline), in a velocity-dependent force field (adaptation; 25 N sm−1) and once again in a null force field (de-adaptation). Active or sham tDCS was directed to the motor cortex representation of biceps brachii muscle during the adaptation phase of the motor learning protocol. During the adaptation phase, the global error in arm reaching (summed error from an ideal trajectory) was similar in both tDCS conditions. However, active tDCS induced a significantly greater global reaching (overshoot) error during the early stage of de-adaptation compared to the sham tDCS condition. The overshoot error may be representative of the development of a greater predictivemovement to overcome the expected imposed force. An estimate of the predictive, initial movement trajectory (signed error in the first 150 ms of movement) was significantly augmented during the adaptation phase with active tDCS compared to sham tDCS. Furthermore, this increase was linearly related to the change of the overshoot summed error in the de-adaptation process. Together the results suggest that anodal tDCS augments the development of an internal model of the novel adapted movement and suggests that the primary motor cortex is involved in adaptation of reaching movements of healthy human subjects

    Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

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    BACKGROUND: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. METHODS AND FINDINGS: Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score 64 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. CONCLUSIONS: The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations

    Systems and Methods for Advanced Rapid Imaging and Analysis for Earthquakes

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    Many embodiments provide a hybrid data processing system (HySDS) of an end-to-end geodetic imaging data system enabling near-real-time science, assessment, response, and rapid recovery. The HySDS may be an operation data processing system that integrates data from many different geodetic data sources and/or sensors, including interferometric synthetic aperture radar (InSAR), GPS, pixel tracking, seismology, and/or modeling, and processes the data to generate actionable high quality science data products. The HySDS may provide for an automated imaging and analysis capabilities that is able to handle the imminent increases in raw data from new and existing geodetic monitoring sensor systems

    Treatment of an Intramammary Bacterial Infection with 25-Hydroxyvitamin D3

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    Deficiency of serum levels of 25-hydroxyvitamin D3 has been correlated with increased risk of infectious diseases such as tuberculosis and influenza. A plausible reason for this association is that expression of genes encoding important antimicrobial proteins depends on concentrations of 1,25-dihydroxyvitamin D3 produced by activated immune cells at sites of infection, and that synthesis of 1,25-dihydroxyvitamin D3 is dependent on the availability of 25-hydroxyvitamin D3. Thus, increasing the availability of 25(OH)D3 for immune cell synthesis of 1,25-dihydroxyvitamin D3 at sites of infection has been hypothesized to aid in clearance of the infection. This report details the treatment of an acute intramammary infection with infusion of 25-hydroxyvitamin D3 to the site of infection. Ten lactating cows were infected with in one quarter of their mammary glands. Half of the animals were treated intramammary with 25-hydroxyvitamin D3. The 25-hydroxyvitamin D3 treated animal showed significantly lower bacterial counts in milk and showed reduced symptomatic affects of the mastitis. It is significant that treatment with 25-hydroxyvitamin D3 reduced the severity of an acute bacterial infection. This finding suggested a significant non-antibiotic complimentary role for 25-hydroxyvitamin D3 in the treatment of infections in compartments naturally low in 25-hydroxyvitamin D3 such as the mammary gland and by extension, possibly upper respiratory tract infections

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Vitamin D Signaling in the Bovine Immune System: A Model for Understanding Human Vitamin D Requirements

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    The endocrine physiology of vitamin D in cattle has been rigorously investigated and has yielded information on vitamin D requirements, endocrine function in health and disease, general metabolism, and maintenance of calcium homeostasis in cattle. These results are relevant to human vitamin D endocrinology. The current debate regarding vitamin D requirements is centered on the requirements for proper intracrine and paracrine vitamin D signaling. Studies in adult and young cattle can provide valuable insight for understanding vitamin D requirements as they relate to innate and adaptive immune responses during infectious disease. In cattle, toll-like receptor recognition activates intracrine and paracrine vitamin D signaling mechanism in the immune system that regulates innate and adaptive immune responses in the presence of adequate 25-hydroxyvitamin D. Furthermore, experiments with mastitis in dairy cattle have provided in vivo evidence for the intracrine vitamin D signaling mechanism in macrophages as well as vitamin D mediated suppression of infection. Epidemiological evidence indicates that circulating concentrations above 32 ng/mL of 25-hydroxyvitamin D are necessary for optimal vitamin D signaling in the immune system, but experimental evidence is lacking for that value. Experiments in cattle can provide that evidence as circulating 25-hydroxyvitamin D concentrations can be experimentally manipulated within ranges that are normal for humans and cattle. Additionally, young and adult cattle can be experimentally infected with bacteria and viruses associated with significant diseases in both cattle and humans. Utilizing the bovine model to further delineate the immunomodulatory role of vitamin D will provide potentially valuable insights into the vitamin D requirements of both humans and cattle, especially as they relate to immune response capacity and infectious disease resistance

    Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

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    Background: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. Methods and Findings: Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child–Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26–106 mo) and 39 mo for Taiwanese patients (interquartile range, 12–61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2–3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4–5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score’s prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. Conclusions: The ITA.LI.CA prognostic system includes both a tumor staging—stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)—and a prognostic score—integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations

    Differential Expression of Cytokines in Response to Respiratory Syncytial Virus Infection of Calves with High or Low Circulating 25-Hydroxyvitamin D3

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    Deficiency of serum levels of 25-hydroxyvitamin D3 has been related to increased risk of lower respiratory tract infections in children. Respiratory syncytial virus (RSV) is a leading cause of low respiratory tract infections in infants and young children. The neonatal calf model of RSV infection shares many features in common with RSV infection in infants and children. In the present study, we hypothesized that calves with low circulating levels of 25-hydroxyvitamin D3 (25(OH)D3) would be more susceptible to RSV infection than calves with high circulating levels of 25(OH)D3. Calves were fed milk replacer diets with different levels of vitamin D for a 10 wk period to establish two treatment groups, one with high (177 ng/ml) and one with low (32.5 ng/ml) circulating 25(OH)D3. Animals were experimentally infected via aerosol challenge with RSV. Data on circulating 25(OH)D3 levels showed that high and low concentrations of 25(OH)D3 were maintained during infection. At necropsy, lung lesions due to RSV were similar in the two vitamin D treatment groups. We show for the first time that RSV infection activates the vitamin D intracrine pathway in the inflamed lung. Importantly, however, we observed that cytokines frequently inhibited by this pathway in vitro are, in fact, either significantly upregulated (IL-12p40) or unaffected (IFN-γ) in the lungs of RSV-infected calves with high circulating levels of 25(OH)D3. Our data indicate that while vitamin D does have an immunomodulatory role during RSV infection, there was no significant impact on pathogenesis during the early phases of RSV infection. Further examination of the potential effects of vitamin D status on RSV disease resolution will require longer-term studies with immunologically sufficient and deficient vitamin D levels

    The daily association between affect and alcohol use: a meta-analysis of individual participant data

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    Influential psychological theories hypothesize that people consume alcohol in response to the experience of both negative and positive emotions. Despite two decades of daily diary and ecological momentary assessment research, it remains unclear whether people consume more alcohol on days they experience higher negative and positive affect in everyday life. In this preregistered meta-analysis, we synthesized the evidence for these daily associations between affect and alcohol use. We included individual participant data from 69 studies (N = 12,394), which used daily and momentary surveys to assess affect and the number of alcoholic drinks consumed. Results indicate that people are not more likely to drink on days they experience high negative affect, but are more likely to drink and drink heavily on days high in positive affect. People self-reporting a motivational tendency to drink-to-cope and drink-to-enhance consumed more alcohol, but not on days they experienced higher negative and positive affect. Results were robust across different operationalizations of affect, study designs, study populations, and individual characteristics. These findings challenge the long-held belief that people drink more alcohol following increases in negative affect. Integrating these findings under different theoretical models and limitations of this field of research, we collectively propose an agenda for future research to explore open questions surrounding affect and alcohol use.The present study was funded by the Canadian Institutes of Health Research Grant MOP-115104 (Roisin M. O’Connor), Canadian Institutes of Health Research Grant MSH-122803 (Roisin M. O’Connor), John A. Hartford Foundation Grant (Paul Sacco), Loyola University Chicago Research Support Grant (Tracy De Hart), National Institute for Occupational Safety and Health Grant T03OH008435 (Cynthia Mohr), National Institutes of Health (NIH) Grant F31AA023447 (Ryan W. Carpenter), NIH Grant R01AA025936 (Kasey G. Creswell), NIH Grant R01AA025969 (Catharine E. Fairbairn), NIH Grant R21AA024156 (Anne M. Fairlie), NIH Grant F31AA024372 (Fallon Goodman), NIH Grant R01DA047247 (Kevin M. King), NIH Grant K01AA026854 (Ashley N. Linden-Carmichael), NIH Grant K01AA022938 (Jennifer E. Merrill), NIH Grant K23AA024808 (Hayley Treloar Padovano), NIH Grant P60AA11998 (Timothy Trull), NIH Grant MH69472 (Timothy Trull), NIH Grant K01DA035153 (Nisha Gottfredson), NIH Grant P50DA039838 (Ashley N. Linden-Carmichael), NIH Grant K01DA047417 (David M. Lydon-Staley), NIH Grant T32DA037183 (M. Kushner), NIH Grant R21DA038163 (A. Moore), NIH Grant K12DA000167 (M. Potenza, Stephanie S. O’Malley), NIH Grant R01AA025451 (Bruce Bartholow, Thomas M. Piasecki), NIH Grant P50AA03510 (V. Hesselbrock), NIH Grant K01AA13938 (Kristina M. Jackson), NIH Grant K02AA028832 (Kevin M. King), NIH Grant T32AA007455 (M. Larimer), NIH Grant R01AA025037 (Christine M. Lee, M. Patrick), NIH Grant R01AA025611 (Melissa Lewis), NIH Grant R01AA007850 (Robert Miranda), NIH Grant R21AA017273 (Robert Miranda), NIH Grant R03AA014598 (Cynthia Mohr), NIH Grant R29AA09917 (Cynthia Mohr), NIH Grant T32AA07290 (Cynthia Mohr), NIH Grant P01AA019072 (P. Monti), NIH Grant R01AA015553 (J. Morgenstern), NIH Grant R01AA020077 (J. Morgenstern), NIH Grant R21AA017135 (J. Morgenstern), NIH Grant R01AA016621 (Stephanie S. O’Malley), NIH Grant K99AA029459 (Marilyn Piccirillo), NIH Grant F31AA022227 (Nichole Scaglione), NIH Grant R21AA018336 (Katie Witkiewitz), Portuguese State Budget Foundation for Science and Technology Grant UIDB/PSI/01662/2020 (Teresa Freire), University of Washington Population Health COVID-19 Rapid Response Grant (J. Kanter, Adam M. Kuczynski), U.S. Department of Defense Grant W81XWH-13-2-0020 (Cynthia Mohr), SANPSY Laboratory Core Support Grant CNRS USR 3413 (Marc Auriacombe), Social Sciences and Humanities Research Council of Canada Grant (N. Galambos), and Social Sciences and Humanities Research Council of Canada Grant (Andrea L. Howard)
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