Despite considerable efforts to control tuberculosis (TB) among Ethiopian immigrants in Israel, an outbreak of TB among second-generation Ethiopian immigrants that involved native Israelis occurred between January 2011 and December 2019. The aim of this article is to report on this outbreak and discuss the patient and health system barriers that led to its propagation. Overall, 13 culture-positive TB patients were diagnosed in this outbreak. An additional 36 cases with identical mycobacterium tuberculosis genotypes were identified through cross-checking with the National TB Laboratory Registry. Among the 32 close contacts of the index case, 18 (56.3%) reported for screening and treatment of latent TB infection (LTBI) was recommended for 11 (61.1%) of them. However, none completed treatment and eight eventually developed TB. Of the 385 close contacts identified in this outbreak, 286 (74.3%) underwent contact investigation, 154 (53.8%) were recommended LTBI treatment, but only 26 (16.9%) completed the treatment. Routine contact investigation and treatment practice measures failed to contain the cascade of infection and disease, leading to the spread of the infecting strain of TB. This report highlights the challenges to identify the high-risk group and address barriers to care among such a vulnerable population.

OBJECTIVES/GOALS: The role of the vaginal microbiome (VM) in HIV disease progression is poorly understood. We examined VMs of HIV+ Elite Controllers (ECs) and HIV+ Long-Term Non-Progressors (LTNPs) compared to controls: HIV-positive antiretroviral (ARV) treated (HIV+ATs) and HIV-negative women in the Women’s Interagency HIV Study (DC/Chicago/Atlanta sites). METHODS/STUDY POPULATION: VMs were surveyed via both V3/V4 region of 16S rRNA gene amplicon sequencing and metagenomics sequencing in 67 women across 4 study groups: 1) LTNPs (CD4 >500 cells/mL for 5+ years without ARVs) (n = 7) and 2) ECs (HIV RNA <80 copies/mL for 2+ years without ARVs) (n = 8), matched with 3) HIV+ ATs (on ARVs for ≥1 year with CD4 increase ≥100 cells/mm3) (n = 34), and 4) HIV- women (n = 18). Metagenomes were characterized from specimens collected at two time points: 1) vaginal swabs collected 2016-2017 (n = 62) and 2) cervicovaginal lavage collected 2002-2016 (n = 35; DC/Chicago only). We used VIRGO (human vaginal non-redundant gene catalog), a newly developed referencing framework to comprehensively catalog VM gene content, taxonomy and functions. RESULTS/ANTICIPATED RESULTS: Women were 89% African American with a mean age of 46 years (SD 8.8). The most prevalent species were Gardnerella vaginalis (predominant in 34%), Lactobacillus iners (predominant in 21%), and L. crispatus (predominant in 14%). 90% of LTNP and 45% of EC samples were Lactobacillus-dominant vs. 28% of HIV- and 30% of HIV+ATs. L. crispatus and L. iners in ECs/LTNPs had significantly different gene content and greater gene richness vs. controls. G. vaginalis-predominant communities were found in 66% of HIV- and 68% of HIV+ATs, compared to 46% of EC and 0% of LTNP. The G. vaginalis strains present in EC/LTNP also showed significantly lower gene richness and different gene content vs. controls. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest unique VM communities among EC/LTNP, and led us to hypothesize that differential regulation of vaginal immunity drives the observed differences. The similarity between VMs of HIV- and HIV+ATs warrants further study. Larger longitudinal VM studies are needed to assess associated functional pathways and understand the etiology of VM association with HIV progression. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest to disclose.

Introduction

Pharmacological treatment have a key role in themanagement of Severe Mental Illness, reducing hospitalization and acute episodes, supporting and enhancing psychotherapy and recovery process. In aninstitutional pathway to remission and recovery it’s much better if thecharacteristics of chosen drugs worktogether with other kind of interventions. DSM-5 includes a new specifier 'withmixed features” for mood episodes, considering by clinicians difficult-to-treatand associated with a poorer prognosis.

The number of people avoiding gluten is growing in many Western countries. However, little information is available on their sociodemographic and dietary profiles. We aimed to describe sociodemographic, behavioural and dietary profiles of participants avoiding gluten in the NutriNet-Santé cohort. Participants of the NutriNet-Santé cohort – excluding coeliac patients – who completed a questionnaire about food exclusions, with complete data on sociodemographic characteristics and dietary intake were included (n 20 456). Food group consumptions and nutrient intakes according to self-reported avoidance of gluten were estimated using ANCOVA adjusted for age, sex and daily energy intake. Based on principal component analysis, three dietary patterns (DP) were identified. Association between DP and avoidance of gluten was investigated using multivariate logistic regression. All data were weighted on the French census. A total of 10·31 (95 % CI 9·90, 10·73) % of the participants declared avoiding gluten, of which 1·65 % totally. They were more likely to be women, older persons, non-smokers, to have a lower educational level and declared more food intolerances. They had higher consumption of fruit, vegetables and lower consumption of dairy products, salty/sweet and fatty foods and alcohol. After adjustments on confounders, a healthy dietary pattern was positively associated with total gluten avoidance (ORQuintile5vsQuintile1 = 14·44, 95 % CI 8·62, 24·19). Our study highlighted that, in this population, individuals who avoid gluten from their diet tend to have a diet more favourable to health. These results can serve as a basis for future studies investigating the potential consequences of a gluten-free diet in non-coeliac population.

Background: There are only few studies approaching the prevalence and cause of stroke in children and adults with Down Syndrome (DS). Methods: We did a retrospective study of our cohort of 4962 patients of Jerome Lejeune Institute since 2007. We collected age of stroke, clinical presentation, cause (TOAST classification), treatment and clinical course. Results: We identified 20 patients from 6 to 56 years old .In all cases, it was a stroke of ischemic origin.: 8 children with a prevalence of 0.33%. 4 had a cardio-embolic origin, 3 secondary to Moya-Moya syndrome and one of undetermined origin. 12 adults (21 to 52 years old) with a prevalence of 0.46%.The majority of the causes of these ischemic strokes are indeterminate (9 of 12), Conclusions: We found a low prevalence and an ischemic cause in all cases of stroke, which differs from the general population. For pediatric stroke, the causes are expected thromboembolic in a context of heart disease most often or secondary to a Moya-Moya syndrome. For adult strokes, the average age is younger than that in the general population and the cause is indeterminate in most cases. We must better explore our patients to identify the risk factors in DS population.

Background: Down syndrome (DS) is the most common genetic cause of intellectual disability.Although progress in managing co-morbidities has improved life expectancy, no therapeutic options have showed to significantly improve intellectual deficiencies.The current focus of the pharmacological treatment of DS is on the improvement of the cognitive impairment that is probably due to neurodevelopmental alterations,neurotransmitter alterations and neurodegeneration,and is also targeted to the overexpression of selected genes on HSA21. Methods: We review the clinical trials of the last 5 years focusing on the cognitive improvement of children with DS. Results: We report the results of therapeutic trials concerning selective negative allosteric regulators of the GABAAa5 receptor, NMDA antagonists, Kinase inhibitors of DYRK1A, folinic acid and thyroid hormone supplementation, activators of serotonergic and cholinergic system. Conclusions: The incomplete understanding of individual phenotypic variability, natural history, lack of biomarkers, no adapted neuropsychological tests, placebo effect, epigenetic effect have limited our capacity to succeed, even when promising drugs are tested.We need new tools and models will allow a better understanding of the pathophysiology. We also need to create more sensitive and realistic outcome mesures to quantify disease and therapeutic efficacy. The association of different therapeutic agents (epidrugs included) with cognitive stimulation could be a future strategy.

Campylobacteriosis, the most frequent bacterial enteric disease, shows a clear yet unexplained seasonality. The study purpose was to explore the influence of seasonal fluctuation in the contamination of and in the behaviour exposures to two important sources of Campylobacter on the seasonality of campylobacteriosis. Time series analyses were applied to data collected through an integrated surveillance system in Canada in 2005–2010. Data included sporadic, domestically-acquired cases of Campylobacter jejuni infection, contamination of retail chicken meat and of surface water by C. jejuni, and exposure to each source through barbequing and swimming in natural waters. Seasonal patterns were evident for all variables with a peak in summer for human cases and for both exposures, in fall for chicken meat contamination, and in late fall for water contamination. Time series analyses showed that the observed campylobacteriosis summer peak could only be significantly linked to behaviour exposures rather than sources contamination (swimming rather than water contamination and barbequing rather than chicken meat contamination). The results indicate that the observed summer increase in human cases may be more the result of amplification through more frequent risky exposures rather than the result of an increase of the Campylobacter source contamination.

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.

The proposed changes to the Common Rule, described in the recent Advanced Notice of Proposed Rulemaking (ANPRM), come more than 20 years after the U.S. Department of Health and Human Services adopted the Rule in 1991. Since that time, human subjects research has changed in significant ways. Not only has the volume of clinical research grown dramatically, this research is now regularly conducted at multiple collaborative sites that are often outside of the United States. Research takes place not only in academic medical centers, but also at outpatient clinics, community hospitals, and other nontraditional venues. In addition, technological advances, such as sophisticated computer software programs, the Internet, social media, new research methods, and mobile applications have exponentially increased the volume of data available and the possibilities for accessing, analyzing, and sharing that data.

Information is lacking in Canada on the frequency of exposures of healthy people to enteric pathogen sources (i.e. water, food, animal contact) at the community level. This information is critical to develop more robust risk assessments and prioritize control measures. A 12-month-long cross-sectional telephone survey of 1200 healthy individuals in a sentinel community was performed. Survey respondents were divided into three recall period groups (3, 7, 14 days). The occurrence of 46 exposures (including water, animal contact, environmental contact and high-risk foods) was assessed per recall period. Effect of age, gender, and season on exposures was modelled and frequencies of exposure were extrapolated. Thirty-five exposures had similar occurrences across recall periods. Age was significant for 23 exposures, season for 18, and gender for three. Exposures that vary by age and season (i.e. bottled water, swimming, etc.) warrant consideration when investigating and analysing cases of enteric illness.

A series of 2277 Leishmania strains from Old World visceral leishmaniasis foci, isolated between 1973 and 2008, were studied by isoenzyme analysis. The strains were obtained from humans, domestic and wild carnivores, rodents and phlebotomine sandflies, and came from 36 countries. In all, 60 different zymodemes were identified and clustered by a phenetic analysis into 3 different groups corresponding to the typically visceralizing species L. donovani (20 zymodemes, 169 strains), L. archibaldi (3 zymodemes, 46 strains) and L. infantum (37 zymodemes, 2,062 strains). The taxonomic position of these isoenzymatic groups is discussed in view of contradictory results obtained from recent molecular studies.

This study provides a comprehensive epidemio-clinical picture of sporadic, domestically acquired cases of amoebiasis, cryptosporidiosis and giardiasis in one Canadian community based on patient symptom, outcome and exposure data from an enhanced surveillance system. It yields valuable data for estimating the burden of those diseases including the proportion of bloody diarrhoea, hospitalization, and disease duration. Age differences were observed by incidence rate and for some clinical information and exposures to risk factors. For each of the three diseases, the animal/environment-to-person route was the most common possible main transmission route according to the exposure reported, whereas the person-to-person route was the least common. Exposure was higher for the 10–24 years age group of giardiasis cases for swimming in recreational waters (79%) and attending a barbeque (50%). Therefore, comparisons between groups of cases or extrapolation of results when estimating the burden of illness should be adjusted for age.

Salmonella Enteritidis has emerged as the most prevalent cause of human salmonellosis in Canada. Recent trends of S. Enteritidis subtypes and their potential sources were described by integrating Salmonella data from several Canadian surveillance and monitoring programmes. A threefold increase in S. Enteritidis cases from 2003 to 2009 was identified to be primarily associated with phage types 13, 8 and 13a. Other common phage types (4, 1, 6a) showed winter seasonality and were more likely to be associated with cases linked to international travel. Conversely, phage types 13, 8 and 13a had summer seasonal peaks and were associated with cases of domestically acquired infections. During agri-food surveillance, S. Enteritidis was detected in various commodities, most frequently in chicken (with PT13, PT8 and PT13a predominating). Antimicrobial resistance was low in human and non-human isolates. Continued integrated surveillance and collaborative prevention and control efforts are required to mitigate future illness.

Campylobacteriosis is a leading cause of acute bacterial gastroenteritis. An ecological study was undertaken to explore the association between environmental characteristics and incidence of campylobacteriosis in relation to four age groups and two seasonal periods. A multi-level Poisson regression model was used for modelling at the municipal level. High ruminant density was positively associated with incidence of campylobacteriosis, with a reduced effect as people become older. High poultry density and presence of a large poultry slaughterhouse were also associated with higher incidence, but only for people aged 16–34 years. The effect of ruminant density, poultry density, and slaughterhouses were constant across seasonal periods. Other associations were detected with population density and average daily precipitation. Close contacts with farm animals are probably involved in the associations observed. The specificity of age and season on this important disease must be considered in further studies and in the design of preventive measures.

Recent interest in phase change materials (PCMs) for non-volatile memory applications has been fueled by the promise of scalability beyond the limit of conventional DRAM and NAND flash memory [1]. However, for such solid state device applications, Ge2Sb2Te5 (GST), GeSb, and other chalcogenide PCMs require doping. Doping favorably modifies crystallization speed, crystallization temperature, and thermal stability but the chemical role of the dopant is not yet fully understood. In this work, X-ray Absorption Fine Spectroscopy (XAFS) is used to examine the chemical and structural role of nitrogen doping (N-) in as-deposited and crystalline GST thin films. The study focuses on the chemical and local bonding environment around each of the elements in the sample, in pre and post-anneal states, and at various doping concentrations. We conclude that the nitrogen dopant forms stable Ge-N bonds as deposited, which is distinct from GST bonds, and remain at the grain boundary of the crystallites such that the annealed film is comprised of crystallites with a dopant rich grain boundary.

An understanding of the effect of cumulative radiation damage on the integrity of ceramic wasteforms for plutonium and minor actinide disposition is key to the scientific case for safe disposal. Alpha recoil due to the decay of actinide species leads to the amorphisation of the initially crystalline host matrix, with potentially deleterious consequences such as macroscopic volume swelling and reduced resistance to aqueous dissolution. For the purpose of laboratory studies the effect of radiation damage can be simulated by various accelerated methodologies. The incorporation of short-lived actinide isotopes accurately reproduces damage arising from both alpha-particle and the heavy recoil nucleus, but requires access to specialist facilities. In contrast, fast ion implantation of inactive model ceramics effectively simulates the heavy recoil nucleus, leading to amorphisation of the host crystal lattice over very short time-scales. Although the resulting materials are easily handled, quantitative analysis of the resulting damaged surface layer has proved challenging.

In this investigation, we have developed an experimental methodology for characterisation of radiation damaged structures in candidate ceramics for actinide disposition. Our approach involves implantation of bulk ceramic samples with 2 MeV Kr+ ions, to simulate heavy atom recoil; combined with grazing incidence X-ray absorption spectroscopy (GI-XAS) to characterise only the damaged surface layer. Here we present experimental GI-XAS data acquired at the Ti and Zr K-edges of ion implanted zirconolite, as a function of grazing angle, demonstrating that this technique can be successfully applied to characterise only the amorphised surface layer. Comparison of our findings with data from metamict natural analogues provide evidence that heavy ion implantation reproduces the amorphous structure arising from naturally accumulated radiation damage.