The REVERE project:Experiments with the application of probabilistic NLP to systems engineering

Despite natural language’s well-documented shortcomings as a medium for precise technical description, its use in software-intensive systems engineering remains inescapable. This poses many problems for engineers who must derive problem understanding and synthesise precise solution descriptions from free text. This is true both for the largely unstructured textual descriptions from which system requirements are derived, and for more formal documents, such as standards, which impose requirements on system development processes. This paper describes experiments that we have carried out in the REVERE1 project to investigate the use of probabilistic natural language processing techniques to provide systems engineering support

Simplifying operations with an uplink/downlink integration toolkit

The Operations Engineering Lab (OEL) at JPL has developed a simple, generic toolkit to integrate the uplink/downlink processes, (often called closing the loop), in JPL's Multimission Ground Data System. This toolkit provides capabilities for integrating telemetry verification points with predicted spacecraft commands and ground events in the Mission Sequence Of Events (SOE) document. In the JPL ground data system, the uplink processing functions and the downlink processing functions are separate subsystems that are not well integrated because of the nature of planetary missions with large one-way light times for spacecraft-to-ground communication. Our new closed-loop monitoring tool allows an analyst or mission controller to view and save uplink commands and ground events with their corresponding downlinked telemetry values regardless of the delay in downlink telemetry and without requiring real-time intervention by the user. An SOE document is a time-ordered list of all the planned ground and spacecraft events, including all commands, sequence loads, ground events, significant mission activities, spacecraft status, and resource allocations. The SOE document is generated by expansion and integration of spacecraft sequence files, ground station allocations, navigation files, and other ground event files. This SOE generation process has been automated within the OEL and includes a graphical, object-oriented SOE editor and real-time viewing tool running under X/Motif. The SOE toolkit was used as the framework for the integrated implementation. The SOE is used by flight engineers to coordinate their operations tasks, serving as a predict data set in ground operations and mission control. The closed-loop SOE toolkit allows simple, automated integration of predicted uplink events with correlated telemetry points in a single SOE document for on-screen viewing and archiving. It automatically interfaces with existing real-time or non real-time sources of information, to display actual values from the telemetry data stream. This toolkit was designed to greatly simplify the user's ability to access and view telemetry data, and also provide a means to view this data in the context of the commands and ground events that are used to interpret it. A closed-loop system can prove especially useful in small missions with limited resources requiring automated monitoring tools. This paper will discuss the toolkit implementation, including design trade-offs and future plans for enhancing the automated capabilities

Outbreak of Serogroup W135 Meningococcal Disease after the Hajj Pilgrimage, Europe, 2000

The 2000 Hajj (March 15–18) was followed by an outbreak of Neisseria meningitidis W135 2a: P1.2,5 in Europe. From March 18 to July 31, 2000, some 90 cases of meningococcal infection were reported from nine countries, mostly the United Kingdom (UK) and France; 14 cases were fatal. Although most early cases were in pilgrims, the outbreak spread to their contacts and then to those with no known pilgrim contact. In France and the UK, the outbreak case-fatality rate was compared with the rate reported from national surveillance. The risk of dying during this outbreak was higher in France and the UK, although the difference was not statistically significant. Prophylaxis for all pilgrims and their household contacts was offered in France; in the UK and other European countries, prophylaxis was recommended only for close contacts. No difference in transmission rates following intervention was detected between France and the UK

Danos genéticos e exposição a pesticidas em trabalhadores agrícolas do Vale San Quintin, Baixa California, México

Various studies have shown the ability of pesticides to induce genetic damage (GD) that can cause health effects. In the present work, a genotoxicological study was conducted monitoring residents from the agricultural region of the San Quintin Valley (SQV), Baja California, Mexico. The objective was to determine if occupational and environmental exposure to pesticides in the region of the SQV is a factor in GD, and to find out if women are more vulnerable to this effect. A questionnaire was administered to 88 residents of the SQV to establish inclusion and exclusion criteria for the study; of these, 40 agreed to participate (25 occupationally exposed to pesticides and 15 environmentally exposed to them), with similar numbers of men and women. All participants signed an informed consent form. The micronuclei technique (MN) was used, which blocks cytokinesis in peripheral blood samples, to evaluate GD by counting the number of MN and Chromatin Bridges in 1000 bi-nucleated cells (BNC). The results of this measure of genetic damage were then correlated with the degree of occupational pesticide exposure of the participants. Environmentally exposed men had less GD than women with MN means of 8.1± (1.83) and 13.1(±1.7) respectively, whereas occupational exposure affected both sexes, men with a mean of MN equal to 15.9 (± 2.9), and women with 18.12 (± 1.7). Based on our results, it can be concluded that occupational exposure to pesticides is a factor in GD, with women showing greater vulnerability than men. The time of exposure at work was shown to be directly related to the increased number of MN.Diferentes estudios muestran la capacidad de los plaguicidas para inducir daño genético (DG) con diversos efectos en la salud. En el presente trabajo se estudia la genotoxicidad en residentes del valle agrícola de San Quintín, Baja California, México (VSQ). El objetivo fue determinar si la exposición laboral y ambiental a plaguicidas en la región del VSQ es un factor de DG y explorar si las mujeres son más vulnerables a dicho efecto. Se aplicó un cuestionario a 88 residentes del VSQ para determinar los factores de inclusión y exclusión del estudio, 40 aceptaron participar, 25 expuestos ocupacionalmente a plaguicidas y 15 ambientalmente expuestos, con similar número de hombres y mujeres. Todos los participantes firmaron un consentimiento informado. Se utilizó la técnica de micronúcleos (MN) por bloqueo de la citocinesis en sangre periférica para evaluar el DG con la frecuencia de MN y Puentes de Cromatina en 1000 células binucleadas (CBN); se exploró la correlación del DG con el tiempo de exposición ocupacional a plaguicidas. Los hombres ambientalmente expuestos tuvieron menos DG que las mujeres con medias de MN de 8,1 (±1,83) y 13,1 (±1,7) respectivamente; en cambio, la exposición laboral afectó a los dos sexos: los hombres tuvieron una media de MN igual a 15,9 (±2,9) y en las mujeres fue 18,1 (±1,7). Se concluye que la exposición laboral a plaguicidas es un factor de DG, las mujeres mostraron mayor vulnerabilidad al DG. El tiempo de exposición laboral se relaciona directamente con el aumento del número de MN.Diferentes estudos mostram a capacidade que os pesticidas possuem para induzir dano genético (DG) com diversos efeitos na saúde. Neste trabalho estudou-se a genotoxicidade em residentes do vale agrícola de San Quintin, Baixa Califórnia, México (VSQ), cujo objetivo foi determinar se a exposição ocupacional e ambiental a pesticidas nesta região é um fator DG e explorar se as mulheres são mais vulneráveis a este efeito. Aplicou-se um questionário a 88 moradores do VSQ para determinar os fatores de inclusão e exclusão no estudo, 40 concordaram em participar dos quais 25 com exposição ocupacional e 15 com exposição ambiental, com um número idêntico de homens e mulheres. Todos os participantes assinaram um termo de consentimento informado. Foi utilizada a técnica de micronúcleos (MN) por bloqueio da citocinese em amostras de sangue periférico para avaliar o DG com a frequência de MN e Pontes de Cromatina em 1000 células binucleadas (CBN); explorou-se a correlação do DG com o tempo de exposição ocupacional a pesticidas. Os homens ambientalmente expostos tiveram menos DG do que as mulheres com médias de MN de 8,1 ± (1,83) y 13,1 (±1,7) respetivamente; por outro lado, a exposição ocupacional afetou os dois sexos: os homens tiveram uma média de MN igual 15,9 (± 2,9) e nas mulheres foi de 18,1 (± 1,7). Concluiu-se que a exposição ocupacional a pesticidas é um facto de DG e as mulheres apresentam maior vulnerabilidade a DG. O tempo de exposição ocupacional está diretamente relacionado com o aumento do número de MN

Large-scale antibody immune response mapping of splenic B cells and bone marrow plasma cells in a transgenic mouse model

Molecular characterization of antibody immunity and human antibody discovery is mainly carried out using peripheral memory B cells, and occasionally plasmablasts, that express B cell receptors (BCRs) on their cell surface. Despite the importance of plasma cells (PCs) as the dominant source of circulating antibodies in serum, PCs are rarely utilized because they do not express surface BCRs and cannot be analyzed using antigen-based fluorescence-activated cell sorting. Here, we studied the antibodies encoded by the entire mature B cell populations, including PCs, and compared the antibody repertoires of bone marrow and spleen compartments elicited by immunization in a human immunoglobulin transgenic mouse strain. To circumvent prior technical limitations for analysis of plasma cells, we applied single-cell antibody heavy and light chain gene capture from the entire mature B cell repertoires followed by yeast display functional analysis using a cytokine as a model immunogen. We performed affinity-based sorting of antibody yeast display libraries and large-scale next-generation sequencing analyses to follow antibody lineage performance, with experimental validation of 76 monoclonal antibodies against the cytokine antigen that identified three antibodies with exquisite double-digit picomolar binding affinity. We observed that spleen B cell populations generated higher affinity antibodies compared to bone marrow PCs and that antigen-specific splenic B cells had higher average levels of somatic hypermutation. A degree of clonal overlap was also observed between bone marrow and spleen antibody repertoires, indicating common origins of certain clones across lymphoid compartments. These data demonstrate a new capacity to functionally analyze antigen-specific B cell populations of different lymphoid organs, including PCs, for high-affinity antibody discovery and detailed fundamental studies of antibody immunity

Inter-professional Service Learning to Increase Students\u27 Understanding of Migrant Latino Health

Learning Objectives At the end of this seminar participants will be able to: 1.Explain the relevance of inter-professional, cultural competent, global health approaches to health assessment and interventions at home and abroad. 2.Identify evidence-based programs to improve target population health, utilizing the CLAS standards to advance health equity, improve quality and help eliminate health disparities. 3.Design a service learning inter-professional health education course with teaching strategies for cultural competency training that utilizes academic and clinical partnerships

BDNF Val66Met modifies the risk of childhood trauma on obsessive-compulsive disorder

Childhood trauma has been linked to the development of later psychopathology, including obsessive-compulsive disorder (OCD). Although evidence exists to suggest that genetic and environmental factors are involved in the aetiology of OCD, little attention has been paid to the interactions that exist between genes and environment. The aim of this study was to investigate gene-by-environment interactions between childhood trauma and the BDNF Val66Met variant in patients with OCD. Childhood trauma was assessed in 134 OCD patients and 188 controls using the Childhood Trauma Questionnaire (CTQ). Linear regression models were used for statistical analyses. Geneeenvironment interactions were estimated by including a combined genotype and CTQ score in the models as interaction terms. All analyses were adjusted for age, gender, CTQ minimisation-denial score and home language by including them in the logistic regression models as covariates. Childhood trauma, specifically emotional abuse and neglect, increased the odds of having OCD significantly (p < 0.001). Although no significant association was observed between BDNF Val66Met and the development of OCD, interaction analysis indicated that the BDNF Met-allele interacted with childhood emotional abuse to increase the risk of OCD significantly in a dose-dependent manner (p < 0.024). To our knowledge, this is one of the first studies to investigate geneeenvironment interactions in OCD, and the findings indicate the importance of collating genetic and environmental variables in future studies.Web of Scienc

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

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

Analysis of early mesothelial cell responses to Staphylococcus epidermidis isolated from patients with peritoneal dialysis-associated peritonitis

The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised. We systematically investigated the early mesothelial cell response to clinical and reference isolates of S. epidermidis using primary mesothelial cells and the mesothelial cell line Met-5A. Using an unbiased whole genome microarray, followed by a targeted panel of genes known to be involved in the human antibacterial response, we identified 38 differentially regulated genes (adj. p-value &lt; 0.05) representing 35 canonical pathways after 1 hour exposure to S. epidermidis. The top 3 canonical pathways were TNFR2 signaling, IL-17A signaling, and TNFR1 signaling (adj. pvalues of 0.0012, 0.0012 and 0.0019, respectively). Subsequent qPCR validation confirmed significant differences in gene expression in a number of genes not previously described in mesothelial cell responses to infection, with heterogeneity observed between clinical isolates of S. epidermidis, and between Met-5A and primary mesothelial cells. Heterogeneity between different S. epidermidis isolates suggests that specific virulence factors may play critical roles in influencing outcomes from peritonitis. This study provides new insights into early mesothelial cell responses to infection with S. epidermidis, and confirms the importance of validating findings in primary mesothelial cells