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When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype., Author summary Opportunistic fungal pathogens commonly acquire extra copies of chromosomes that can provide a fitness benefit under acute stress such as exposure to antifungal agents but how these extra copies affect fungal life-style and interactions with their hosts is poorly understood. Here we show that in C. albicans the acquisition of specific whole chromosome trisomies during oropharyngeal infection in mice results in a commensal-like phenotype. Our data indicate that trisomies of chromosomes 5 and 6 alter several related virulence-associated traits that affect how the host recognizes and responds to C. albicans during oropharyngeal infection, thereby inducing this commensal-like phenotype. Whole genome sequencing revealed that trisomies were mostly maintained in subsequent oral infections and that de novo mutations that arose were not shared among strains. We hypothesize that both in vivo and in vitro phenotypes are likely the result of allelic imbalance of specific genes on the trisomic chromosomes, rather than due to whole chromosome trisomy.

Objective: To share Vietnam’s experiences piloting the integration of viral load (VL) testing into the national HIV sentinel surveillance (HSS) system to better understand the level of HIV viral transmission among people who inject drugs (PWID). Introduction: Vietnam initiated the HSS system in 1994 in selected provinces with high HIV burden. The surveillance has two components: monitor HIV sero-prevalence and risk behaviors among key population including PWID. However, no VL data were collected among HIV infected people. In 2016, Vietnam piloted an added component of VL testing to the existing HSS system. The purpose was to test the feasibility of adding VL testing to the HSS so that VL data among PWID would be available. The pilot was conducted in two provinces in southern Vietnam-Ho Chi Minh City and Long An. It was expected that adding the VL testing to the existing HSS would also save resources and help monitor HIV viral transmission among PWID in the community regardless if they are currently on anti-retroviral therapy (ART). Methods: Male PWIDs were enrolled into 2016 HSS+ following the standard operating procedure (SOP) [1] . Community-based sampling was based on random selection of wards/communes listed in the sampling frame. In each selected ward/commune, all eligible PWID were invited to voluntarily participate in the survey. Eligibility criteria were males 16 years of age or older, reporting injecting drug in the past month, and residing in the selected area. . The survey included an interview using a standardized questionnaire and 7ml blood drawn for HIV testing. Blood specimens were transferred from districts to provincial labs for plasma separation in the same day. Each plasma specimen was divided into three aliquots of 1ml each. One aliquot was used to test for HIV diagnosis at provincial labs, using the national HIV testing strategy III [2] . The remaining 2 aliquots were stored at provincial labs at 2-8 0 C and within 5 days, were shipped to Pasteur Institute in Ho Chi Minh City (PIHCM) where the plasma specimens were stored at -80 0 C. Processing of samples for VL testing was conducted at the end of the survey where all plasma specimen were transferred to PIHCM lab, which was 2 months since the collection of the first blood specimen. VL was undertaken on COBAS AMPLYPREP/COBAS TAQMAN 48, with identification threshold 20 cps/ml and specificity of 100% using Kit CAP-G/CTM HIV-1 V 2.0. The VL testing results were sent back to relevant Provicial AIDS Centers to return to respective participants, within 3 months. Results: Five hundred male PWID (HCMC: 300; LA: 200) were enrolled into 2016 HSS/HSS+ and agreed to provide blood specimen without any refusal. 84 tested positive for HIV (16.8%. HCMC: 15.0%; LA: 19.5%), 43 (51.2%) specimens had unsuppressed VL (>1000 copies/ml) (HCMC: 66.7%; LA: 33.3%), 35 (41.7%) specimens had undetected level (

Objective To describe the implementation process, successes, challenges, and lessons learned of the application of tablet for data collection and data system in HIV sentinel surveillance in Vietnam Introduction Vietnam has routinely monitored HIV sero-prevalence among key populations through its HIV sentinel surveillance system (HSS). In 2010, this system was updated to include a behavioral component (HSS+) among people who inject drugs, female sex workers, and men who have sex with men. HSS+ has historically used a paper-based questionnaire for data collection (1) . At the end of the survey, provincial data were manually entered into computers using EpiData Entry forms (http://www.epidata.dk/) and submitted to the Vietnam Authority of HIV/AIDS Control (VAAC). As a result, feedback to provinces on data issues was not provided until after fieldwork completion. One recent survey used tablets for data collection and found that it saved time, required fewer staff, and reduced costs compared to paper-based data collection (2) . In 2017, Vietnam introduced tablet for behavioral data collection in HSS+ to improve data quality, resource saving, and to provide more timely access to data. Methods Development of data entry forms and data system Survey data entry forms were designed using free Epi Info ™ software for mobile devices (3) and installed on tablets. A SQL database was established via SFPT data transfer to the current database in VAAC’s server. Field data were instantly synced to the national database when the internet signal was available (Picture 1). Real-time data analysis was granted to surveillance staff at all levels using authorized access to the database via Epi Info ™ Cloud Data Analytics (ECDA), dashboards were used to track progress and data quality (Figure 1). HSS+ data were frequently reviewed by the National Surveillance Technical Working Group (NSTWG) and timely feedback was provided. Deployment Manuals and e-leaning materials were developed. The NSTWG conducted a pilot to test the forms and data flow from field to the national database before installed into all tablets. Four to seven tablets were distributed to each province depending on number of HSS+ sites and populations. Surveillance staff at Provincial AIDS Centers (PACs) were trained by the NSTWG on how to use the tablet to interview, check, update, save data, and sync data to cloud and to the national database, and to backup the provincial dataset. They then provided trainings to their local field staff. The NSTWG provided technical assistance and troubleshooting through field visits and online support to help local staff address issues regarding tablet use in addition to other HSS/HSS+ issues. Results Currently, 18 HSS+ provinces have implemented the 2017 HSS+. Of these, nine provinces applied tablets exclusively. Two provinces used tablets, but also used paper-based questionnaires when not enough tablets were available. Seven Global Fund supported provinces used the paper-based questionnaires and entered data into tablets after interview completion due to copies of completed paper-based questionnaires are required by these provincial project management units (PMU) for fund re-imbursement. Additional updates were required after the first few days, which created issues around updating forms once revised forms were sent out by NSTWG. Another challenge was that local staff were not familiar with using tablets at the beginning. Also frequent complaints were mainly on data entry and synchronization regarding participant identity code or a record could not be synced. The NSTWG and PAC staff were able to monitor the HSS+ progress and provided feedback daily. Most commonly, feedbacks were provided on participant codings and site names. Using the tablet did not require staff, time or money for data entry and eliminated data entry errors. In general, staff prefered to use this data collection mode. Conclusions This mobile device application for data collection in routine HSS+ in Vietnam is feasible and accepted. However, harmonization and coordination from the central Global Fund PMU and provincial PMU will be required to successfully roll-out this system in all HSS+ provinces. This application in addition to ECDA help to improve data quality, due to timeliness of the data, is cost saving and reduces workload. Most importantly, better quality and timely data will facilitate preparation for timely local planning and response. References 1. Thanh DC et al. Brief behavioural surveys in routine HIV sentinel surveillance: a new tool for monitoring the HIV epidemic in Vietnam. Western Pacific Surveillance and Response Journal. Vol 6, No. 1/2015 2. National Institute of Hygiene and Epidemiology. HIV/STI Integrated Biological and Behavioural Surveillance in Vietnam. Hanoi, 2014. 3. https://www.cdc.gov/epiinfo/mobile.html

Objective To describe the implementation and preliminary results of returning HIV test results to participants in Vietnam HIV sentinel surveillance. Introduction Knowledge of one’s HIV serostatus helps improve quality of life for those who test positive and decreases the risk of HIV transmission. WHO recommends that all participants in HIV prevalence surveys be provided access to their test results, especially those who test HIV positive [1]. Anonymous Vietnam HIV sentinel surveillance (HSS), implemented since 1994, focuses on people who inject drugs (PWID), female sex workers (FSW), and men who have sex with men (MSM) [2]. According to national guidelines, the HIV testing algorithm for surveillance purposes was based on two tests whereas the diagnostic algorithm for individuals was based on three tests. Thus, surveillance test results could not be returned to participants [3] who were instead encouraged to learn their HIV serostatus by testing at public confirmatory testing sites. In 2015, a three-test strategy was applied as part of HSS so that test results could be returned to participants. Methods In 2015, return of HIV test results was implemented as a pilot in 16 HSS provinces. HSS participants were asked to identify which of the designated HIV testing and counselling centers (HTC) in the province was most convenient for them. Participants were then given appointment cards with an assigned survey ID to receive their test results at the chosen venue at a specific date and time. Specimens, with assigned survey IDs, were transferred to the respective HIV laboratory at the Province AIDS Center (PAC) for confirmatory testing. The same three-test algorithm was used for surveillance purposes as well as to return confirmatory test results to participants [3]. Final test results were classified as “positive”, “negative” or “indeterminate”. HIV confirmatory test results were made available at all designated HTC in the provinces within 10 days after blood collection; thus, if a participant presented at a location, date or time that differed from the appointment card, s/he could still receive the test result. In some settings in which provinces integrated HSS with either static or mobile HTC, three rapid tests were used at point-of-care so that same-day test results were available. In this case, participants received test results at the end of the specified time regardless of their infection status. At the HTC, individuals showed their appointment cards. The IDs were used to identify the correct test results which were then given verbally to participants by HTC counsellors. Test results were not returned by phone or email. Individuals who tested positive were immediately referred to HIV treatment and other available health/social services in the province. The proportion of participants who received their test results was calculated for each survey group and province. Results The number of provinces that reported returning of HIV test results in 2015 and 2016 were 14 and 15, respectively. Overall, among 15,530 persons tested through HSS in 2015 and 2016, 7,354 persons returned to receive their test results. The proportion of participants who returned for test results varied by province and survey population (table 1). In some provinces where HSS was integrated with HTC, such as Hai Phong and Dong Thap, 100% of participants received their test results within a day [4]. Conclusions Returning HIV test results to HIV surveillance participants is feasible and beneficial in low-income countries like Vietnam. This enhancement facilitates participants learning their serostatus and contributes toward Vietnam’s achievement of HIV control [4]. Based on the pilot experiences, Vietnam Ministry of Health decided to extend test result notifications to all 20 HSS provinces in 2017. Key factors that contributed to the success of the activity were fast turnaround time, roles and level of commitment of PAC, and coordination between the survey and HTC. The returning rate in HSS 2015 and 2016 are promising but these could be improved further. Better coordination and commitment between the survey and HIV testing service are needed to further increase return rates so that HIV-positive individuals can learn their serostatus and be better linked to care and treatment services. References 1. WHO, Guidelines for second generation HIV surveillance: An update: Know your epidemic, 2013. 2. VAAC, Guidance for epidemiological surveillance of HIV/AIDS & sexually transmitted infections , 2012. 3. MOH, National guideline on HIV serology testing , in Decision 1098/QD-BYT , 2013. 4. VAAC, Primarily results of HSS, 2016.

ObjectiveTo describe an exercise to identify priority provinces to be focused in the Vietnam National HIV Sentinel Surveillance (HSS).IntroductionThe Vietnam National HSS was established in 1994. In the late 1990s and early 2000s, when the epidemic was increasing rapidly, the HSS helped with the intensive close monitoring of the HIV epidemic. In its first 10 years, the HSS was rapidly expanded from 6 to 40 provinces and in some years, it was conducted semi-annually. After two decades, the HIV epidemic situation has changed. In most provinces, HIV prevalence has reported to have declined. Compared to the peak period, the HIV prevalence among key populations (KP) in the past decade decreased from 40-60% to 20% or lower. In many provinces, HIV prevalence was less than 10% among people who inject drugs (PWID) and less than 3% among female sex workers (FSW), and among men who have sex with men (MSM) (Table 1). At the same time, the HIV programme has since been scaled up widely with various interventions and expanded to most of the 63 provinces. In 2014, the government of Vietnam and international stakeholders conducted a joint review of the health sector response to the HIV epidemic and concluded that for better monitoring of the epidemic, a more focused and higher quality surveillance system was needed(1). In 2015, surveillance stakeholders conducted a detailed review of the HSS to discuss prioritization of the surveillance activities.MethodsThe prioritization exercise followed a principle that the HSS should be conducted in locations where there is a large population of KP with a high HIV prevalence and it is feasible to implement. Criteria for prioritizing provinces for inclusion were: 1) a high estimated KP size; 2) high HIV prevalence, measured as a 5 year (2011-2015) average prevalence (P); 3) few years with low HIV prevalence, defined as P

Objectives: Smoking is associated with adverse health outcomes among drug users, including those in treatment. To date, however, there has been little evidence about smoking patterns among people receiving opioid-dependence treatment in developing countries. We examined self-reported nicotine dependence and associated factors in a large sample of opioid-dependent patients receiving methadone maintenance treatment (MMT) in northern Vietnam. Setting: Five clinics in Hanoi (urban area) and Nam Dinh (rural area). Participants: Patients receiving MMT in the settings during the study period. Primary and secondary outcome measures: We collected data about smoking patterns, levels of nicotine dependence and other covariates such as socioeconomic status, health status, alcohol use and drug use. The Fagerstrom test was used to measure nicotine dependence (FTND). Logistic regression and Tobit regression were employed to examine relationships between the smoking rate, nicotine dependence and potentially associated variables. Results: Among 1016 drug users undergoing MMT (98.7% male), 87.2% were current smokers. The mean FTND score was 4.5 (SD 2.4). Longer duration of MMT (OR 0.98, 95% CI 0.96 to 0.99) and being HIV-positive (OR 0.46, 95% CI 0.24 to 0.88) were associated with lower likelihood of smoking. Being employed, older age at first drug injection and having long duration of MMT were inversely related with FTND scores. Higher age and continuing drug and alcohol use were significantly associated with higher FTND scores. Conclusion: Smoking prevalence is high among methadone maintenance drug users. Enhanced smoking cessation support should be integrated into MMT programmes in order to reduce risk factors for cigarette smoking and improve the health and well-being of people recovering from opiate dependence.

Histone deacetylases (HDACs) silence genes by deacetylating lysine residues in histones and other proteins. HDAC inhibitors represent a new class of compounds with anti-inflammatory activity. This study investigated whether treatment with a broad spectrum HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), would prevent cardiac fibrosis, part of the cardiovascular remodelling in deoxycorticosterone acetate (DOCA)-salt rats.Control and DOCA-salt rats were treated with SAHA (25 mg x kg(-1) x day(-1) s.c.) for 32 days. Changes in cardiovascular structure and function were assessed by blood pressure in vivo and in Langendorff perfused hearts, ventricular papillary muscle and in aortic rings in vitro. Left ventricular collagen deposition was assessed by histology.Administration of SAHA to DOCA-salt rats attenuated the following parameters: the increased concentration of over 20 pro-inflammatory cytokines in plasma, increased inflammatory cell infiltration and interstitial collagen deposition, increased passive diastolic stiffness in perfused hearts, prolongation of action potential duration at 20% and 90% of repolarization in papillary muscle, development of left ventricular hypertrophy, systolic hypertension and changes in vascular dysfunction.The HDAC inhibitor, SAHA, attenuated the cardiovascular remodelling associated with DOCA-salt hypertensive rats and improved cardiovascular structure and function, especially fibrosis, in the heart and blood vessels, possibly by suppressing inflammation. Control of cardiac histone or non-histone protein acetylation is a potential therapeutic approach to preventing cardiac remodelling, especially cardiac fibrosis.

Advancements in missile technology have made cruise missile capability available worldwide. Current US naval weapon systems lack full interoperability across multiple platforms and full integration of detection, control, and engagement processes against incoming targets. The key to defeating future threats to our military assets is in gaining additional reaction time. This can be accomplished by leveraging collective sensor detection data throughout the battlespace, utilizing the FORCEnet data resources to evaluate the threat, and engaging the threat with a tiered defense. The objective of this capstone project is to address the above issues through the use of Open Architecture (OA) within a FORCEnet environment. This report focuses on the development of a conceptual architecture for Cruise Missile Defense (CMD) that combines FORCEnet architecture requirements with Program Executive Office of Integrated Warfare Systems (PEO IWS) OA functional architecture technical requirements. Further, this conceptual architecture is compared with PEO IWS's functional architecture via a series of systems engineering diagrams. These diagrams culminate in a simulation model that analyzes and determines the validity of the conceptual architecture. Results from the simulation model show that the conceptual architecture performed significantly better than PEO IWS's. These results are attributed to the addition of a re-engagement loop called Observe-Orient-Decide-Act (OODA).