Evaluation of the feasibility and efficacy of point-of-care antibody tests for biomarker guided management of COVID-19.

BACKGROUND: Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests. METHODS: COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome. RESULTS: While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes. CONCLUSIONS: Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard.

STOP-HCV-HCC Program: Privacy-Preserving Innovation for Remote Data Access Analytics at Federally Qualified Health Centers in South Texas.

STOP-HCV-HCC program to screen and treat hepatitis C, vaccinate for hepatitis B, and prevent hepatocellular carcinoma is implementing a cloud-based privacy-preserving platform to overcome electronic health record barriers to reporting, without data transfer, at four federally qualified health centers in South Texas, USA.

Comparison of ultrasound-guided sacral erector spinae plane block and caudal epidural block for analgesia in paediatric patients undergoing hypospadias repair: A double-blind, randomised controlled trial.

Background and Aims: Caudal block is more frequently used in children for postoperative analgesia. However, its disadvantage is its short duration. Erector spinae plane block (ESPB) at the sacral level can potentially block the pudendal nerve. It may prove an alternative to caudal block for hypospadias repair regarding time to first rescue analgesia. Methods: Fifty children of 2-7 years of age were included. After induction of general anaesthesia, Group I (n = 25) was given ultrasound-guided sacral ESPB with 1 ml/kg of 0.25% bupivacaine and Group II (n = 25) was given caudal block with 0.5 ml/kg of 0.25% bupivacaine. Postoperatively at face, leg, activity, cry, consolability (FLACC) score ≥4, rescue analgesia was given using intravenous 15 mg/kg paracetamol. The primary outcome was to compare time to first rescue analgesia, and secondary outcomes were intraoperative haemodynamic parameters, fentanyl consumption, postoperative FLACC score and analgesic consumption in 24 h. Continuous variables were compared using the independent sample t-test or Mann-Whitney test, and categorical variables were compared using the Chi-square test. Results: The mean time to first rescue analgesia was 21.30 (standard deviation [SD]: 3.06) h in Group I and 9.36 (SD: 1.71) h in Group II (P < 0.001) (mean difference -11.94 [95% CI: -13.39, -10.48]). The FLACC score was significantly higher (P < 0.05) postoperatively at 8, 10, 12 and 18 h in Group II. Mean postoperative analgesic consumption was 310.5 (SD: 72.69) mg in Group I and 615.6 (SD: 137.51) mg in Group II (P < 0.001) (mean difference 30.5 [95% CI: 236.41, 373.78]). Conclusion: Sacral ESPB is better regarding time to first rescue analgesia than caudal block in paediatric patients undergoing hypospadias repair.

Choice of antiretroviral therapy has low impact on weight gain.

OBJECTIVE: Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to 'anchor' drugs [protease inhibitors (PI), nonnucleoside reverse transcriptase inhibitors (NNRTI) or INSTIs] and exposure to nucleoside reverse transcriptase inhibitors (NRTIs). DESIGN: In this cohort of antiretroviral drug-naive patients who initiated ART from 2008-2022, we analyzed BMI gain for eight contemporary 'anchor' drugs and three contemporary NRTIs during the first 3 years of ART. We censored patients if they stopped, switched, or added another antiretroviral drug to their regimen. METHODS: We used generalized estimating equations (GEE) to assess the association between BMI gain and choice of ART and a nonlinear mixed model for the marginal coefficients of determination. We adjusted for time, baseline demographic and HIV-characteristics, and time-updated HIV and substance use-related variables. RESULTS: The median BMI gain in 4 194 patients over 3 years was + 1.9 kg/m 2 [interquartile range (IQR) 0.1-4.1]. Most patients were black (55%) and men (77%). Multivariable modeling from 20 528 BMI measurements revealed that the type of ART accounted for just 9% of the predicted BMI change. Only efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) were independently associated with (lower) weight gain but no differences were observed between INSTIs, PIs, and rilpivirine, or between TAF and abacavir. CONCLUSION: The choice of initial ART had little impact on weight gain. INSTIs or TAF were not independently associated with weight change after ART initiation, but EFV and TDF were.

Evaluation of USG-guided novel sacral erector spinae block for postoperative analgesia in pediatric patients undergoing hypospadias repair: A randomized controlled trial.

Background and Aims: Erector spinae plane block (ESPB) has been found to be simple, safe, and effective at thoracic and lumbar levels. There is no randomized controlled trial evaluating its effectiveness at sacral level. The present study was conducted to evaluate its effectiveness at sacral level for postoperative analgesia in pediatric patients undergoing hypospadias repair. Material and Methods: Forty children of 2-7 years with ASA grade I or II were included. They were randomly allocated to one of the two groups of 20 patients each. After induction of general anesthesia, patients of group I were given ultrasound-guided sacral ESPB with 1 ml/kg of 0.25% bupivacaine, and patients of group II were not given block. Postoperatively, pain was assessed using face, legs, activity, cry, consolability (FLACC) scale at 0 hour, every 15 min up to 1 hour, every half an hour up to 2 hours, 2 hourly up to 12 hours, and at 18th hour and 24th hour postoperatively. At FLACC score ≥4, rescue analgesia was given using 15 mg/kg paracetamol infusion. Primary objective was to compare postoperative analgesic (paracetamol) consumption, and secondary objective was time to first rescue analgesia. Results: Mean postoperative paracetamol consumption was 360 ± 156.60 mg in group I and 997.50 ± 310.87 mg in group II (P = 0.001). Time to first rescue analgesia was 906 ± 224.51 min in group I and 205.00 ± 254.92 min in group II (P = 0.001). Conclusion: Sacral ESPB has been found to be effective in reducing postoperative analgesic consumption in pediatric patients undergoing hypospadias repair.

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.

BACKGROUND: Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes. METHODS: In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery. FINDINGS: The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors. INTERPRETATION: Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment. FUNDING: US National Institutes of Health.

Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. RESULTS: Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. CONCLUSIONS: Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

"Do We Stay or Do We Go?" The Impact of Anti-LGBTQ+ Legislation on the HIV Workforce in the South.

The human immunodeficiency virus (HIV) workforce continues to face a crisis, particularly in the southern United States. Adding to known issues of administrative burden and less competitive compensation, recent anti- lesbian, gay, bisexual, transgender and queer (LGBTQ+) legislation threatens the already strained HIV workforce. HIV care providers advocate for all aspects of their patient's lives, including those needing gender-affirming care. The recent legislative targets against transgender patients, which involves many people with HIV, will clearly add to the burden on individual HIV care providers and therefore the HIV workforce. Recruitment and retention efforts in states impacted by these laws will become increasingly difficult without advocacy for the patients we serve. The HIV workforce must work together with LGBTQ+ populations to address these recent laws and promote the well-being of all our patients and colleagues.

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978.

Persistent CMV pneumonitis in HIV infection: a case report.

We present a rare case of pathology-proven CMV pneumonitis in a patient with HIV infection after presenting with cough and fever. This presentation was complicated by recurrence of symptoms after treatment in the setting of continued uncontrolled HIV infection. This case raised the importance of further discussion regarding best treatment guidelines for CMV pneumonitis for patients with HIV.

Who Is at Risk for New Hepatitis B Infections Among People With HIV?

Hepatitis B virus (HBV) increases morbidity and mortality among people with HIV (PWH). We retrospectively analyzed HBV incidence among 5785 PWH. Fourteen had newly positive hepatitis B s antigen (mean 5.2 person-years of follow-up, 46.4/100 000 infections/year). These data show gaps in HBV vaccination and in the preventative efficacy of HBV-specific antiretroviral therapy.

Anaesthetic Management of a Child with Parapharyngeal Abscess.

Airway management in a case of parapharyngeal abscess is challenging as there can be airway obstruction during anaesthetic induction. We describe airway management in 13-yr-old child with parapharyngeal abscess scheduled for incision and drainage. Informed consent was taken for publishing this case report.

Efficacy of inferior vena cava collapsibility index and caval aorta index in predicting the incidence of hypotension after spinal anaesthesia- A prospective, blinded, observational study.

Background and Aim: Spinal anaesthesia-induced hypotension (SAIH) is a frequent side effect of spinal anaesthesia. SAIH is usually observed in patients with hypovolemia. Ultrasonography has evolved as a non-invasive tool for volume status assessment. Methods: This prospective, blinded, observational study was conducted on 75 adult patients who required spinal anaesthesia after receiving ethical approval and registering the study. Ultrasonographic evaluation of the aorta and the inferior vena cava (IVC) was done preoperatively, and the IVC collapsibility index (IVCCI) and caval aorta index were calculated. The incidence of SAIH was recorded. The strength of the association between different parameters and SAIH was calculated. To find out the value of the optimal cut-off for the prediction of SAIH, receiver operating characteristic (ROC) analysis for various ultrasound parameters was done. The bidirectional stepwise selection was utilised for multivariate analysis to choose the single best predictor. Results: SAIH was observed in 36 patients. Among demographic parameters, age, female gender, and height showed a medium correlation. Among ultrasonographic measurements, minimum IVC internal diameter (IVCmin) and IVCCI showed a strong association with SAIH. The best parameter regarding area under the ROC curve (AUC) and diagnostic accuracy was IVCCI (0.828 and 85%, respectively). On multivariate analysis, age (95% CI [1.01, 1.12], P = 0.024) and IVCCI (95% CI [1.05, 1.18], P < 0.001) were significant independent predictors. At a cut-off point of ≥43.5%, IVCCI accurately predicted SAIH (sensitivity 81% and specificity 90%). Conclusion: Preoperative ultrasonographic assessment of IVC to evaluate its collapsibility index is a convenient, cost-effective, and reproducible tool for predicting SAIH.

Persistent low prevalence of hepatitis B vaccination among people with HIV: Time for a change?

Hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma and mortality among people living with HIV (PLWH). HBV vaccination provides protection from infection; however, vaccination rates are low. We conducted a retrospective analysis at three HIV centres in Texas to determine the proportion of PLWH who received the recommended 3 doses of hepatitis B vaccine within 1 year. Factors associated with vaccination completion were explored. In our sample of three sites in a state with high HIV transmission and high rates of liver disease from 2011 to 2021, showed low rates of hepatitis B vaccination. Among eligible PLWH, only 9% completed the 3-dose hepatitis B vaccine series in 1 year. There is an urgent need to improve HBV vaccination to reach 2030 target for hepatitis B elimination.

Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Understanding the treatment benefit of hyperimmune anti-influenza intravenous immunoglobulin (Flu-IVIG) for severe human influenza.

BACKGROUNDAntibody-based therapies for respiratory viruses are of increasing importance. The INSIGHT 006 trial administered anti-influenza hyperimmune intravenous immunoglobulin (Flu-IVIG) to patients hospitalized with influenza. Flu-IVIG treatment improved outcomes in patients with influenza B but showed no benefit for influenza A.METHODSTo probe potential mechanisms of Flu-IVIG utility, sera collected from patients hospitalized with influenza A or B viruses (IAV or IBV) were analyzed for antibody isotype/subclass and Fcγ receptor (FcγR) binding by ELISA, bead-based multiplex, and NK cell activation assays.RESULTSInfluenza-specific FcγR-binding antibodies were elevated in Flu-IVIG-infused IBV- and IAV-infected patients. In IBV-infected participants (n = 62), increased IgG3 and FcγR binding were associated with more favorable outcomes. Flu-IVIG therapy also improved the odds of a more favorable outcome in patients with low levels of anti-IBV Fc-functional antibody. Higher FcγR-binding antibody was associated with less favorable outcomes in IAV-infected patients (n = 50), and Flu-IVIG worsened the odds of a favorable outcome in participants with low levels of anti-IAV Fc-functional antibody.CONCLUSIONThese detailed serological analyses provide insights into antibody features and mechanisms required for a successful humoral response against influenza, suggesting that IBV-specific, but not IAV-specific, antibodies with Fc-mediated functions may assist in improving influenza outcome. This work will inform development of improved influenza immunotherapies.TRIAL REGISTRATIONClinicalTrials.gov NCT02287467.FUNDINGFunding for this research was provided by subcontract 13XS134 under Leidos Biomedical Research Prime Contract HHSN261200800001E and HHSN261201500003I, NCI/NIAID.

Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia.

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co-infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well-established) differs between HBV-HIV co-infection vs. HBV mono-infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV-HIV Ancillary Study and 105 participants in the HBRN mono-infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p < .05) in the HBV-HIV versus the HBV-only sample (HBeAg: 1.05 vs. 0.51 log10 IU/mL; HBsAg: 3.85 vs. 3.17 log10 IU/mL; HBV RNA: 5.60 vs. 3.70 log10 U/mL; HBcrAg: 6.59 vs. 5.51 log10 U/mL). Conversely, among HBeAg(-) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log10 U/mL) were lower (p < .05) in HBV-HIV vs. HBV-only; HBcrAg levels were similar (4.14 vs. 3.64 log10 U/mL; p = .27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co-infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status.

Derivation of a Protein Risk Score for Cardiovascular Disease Among a Multiracial and Multiethnic HIV+ Cohort.

Background Cardiovascular disease risk prediction models underestimate CVD risk in people living with HIV (PLWH). Our goal is to derive a risk score based on protein biomarkers that could be used to predict CVD in PLWH. Methods and Results In a matched case-control study, we analyzed normalized protein expression data for participants enrolled in 1 of 4 trials conducted by INSIGHT (International Network for Strategic Initiatives in Global HIV Trials). We used dimension reduction, variable selection and resampling methods, and multivariable conditional logistic regression models to determine candidate protein biomarkers and to generate a protein score for predicting CVD in PLWH. We internally validated our findings using bootstrap. A protein score that was derived from 8 proteins (including HGF [hepatocyte growth factor] and interleukin-6) was found to be associated with an increased risk of CVD after adjustment for CVD and HIV factors (odds ratio: 2.17 [95% CI: 1.58-2.99]). The protein score improved CVD prediction when compared with predicting CVD risk using the individual proteins that comprised the protein score. Individuals with a protein score above the median score were 3.10 (95% CI, 1.83-5.41) times more likely to develop CVD than those with a protein score below the median score. Conclusions A panel of blood biomarkers may help identify PLWH at a high risk for developing CVD. If validated, such a score could be used in conjunction with established factors to identify CVD at-risk individuals who might benefit from aggressive risk reduction, ultimately shedding light on CVD pathogenesis in PLWH.

A VME: Versa Module Europa, crate controller for high speed data acquisition of heterogeneous, multi-detector systems.

Modern day complex experiments in physics demand highly efficient data acquisition (DAQ) systems capable of acquiring a large number of signals with a very high resolution and near zero dead time, without compromising on the event rate handling capability. To cater to the ever growing demands of the DAQ systems, an intelligent controller with a sequencer and an in-built busy logic has been developed. The heart of the controller is a field programmable gate array that provides (a) a sequencer engine, which holds a list of read-write commands that will be executed upon receiving a valid trigger, (b) a dual port random access memory divided into two blocks of 16 kbytes, each of which is configured in a ping-pong fashion to support data acquisition and data transfer functionalities simultaneously, thereby reducing the dead time, (c) a busy logic interface that validates the master strobe or trigger, a scalar for triggers received, and a time stamp engine for time stamping the events with 10 ns interval, (d) the Versa Module Europa (VME) backplane interface for 32 bit data transfer standards of the VME, and (e) a superspeed universal serial bus communication interface to transfer the data to a computer/single board computer (SBC). The SBC is capable of booting locally or through net via a preboot execution environment from a netboot server, and it contains the driver, libraries, and data server for data collection. A throughput of 32 megabytes per second (MB/s) has been achieved with an event size of 288 signals at an event rate of 30 kiloevents per second with medium slow slave modules, which may further increase up to 45 MB/s with faster slave modules. The VME controller supports an event size (number of signals) of up to 1023 in a single VME crate. Thus, this sequencer engine based VME crate controller development facilitates collection of a high volume of data with a large number of signals at higher event rates and the least dead time; it is named as Readout Ordained Sequencer Engine.