A novel ppm-precise absolute calibration method for precision high-voltage dividers

The most common method to measure direct current high voltage (HV) down to the ppm-level is to use resistive high-voltage dividers. Such devices scale the HV into a range where it can be compared with precision digital voltmeters to reference voltages sources, which can be traced back to Josephson voltage standards. So far the calibration of the scale factors of HV dividers for voltages above 1 kV could only be done at metrology institutes and sometimes involves round-robin tests among several institutions to get reliable results. Here we present a novel absolute calibration method based on the measurement of a differential scale factor, which can be performed with commercial equipment and outside metrology institutes. We demonstrate that reproducible measurements up to 35 kV can be performed with relative uncertainties below 1 · 10$^{-6}$. This method is not restricted to metrology institutes and offers the possibility to determine the linearity of high-voltage dividers for a wide range of applications

Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort.

Background.  We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods.  We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (>Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results.  Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27-7.20), sCD14 (IRR, 2.17; 95% CI, 1.02-4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01-0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions.  Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function

Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy.

A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium

A novel treatment for anterior shoulder instability: A biomechanical comparison between a patient-specific implant and the Latarjet procedure

BACKGROUND: Anterior glenohumeral instability with &gt;20% glenoid bone loss is a disorder that can be treated with the Latarjet stabilizing procedure; however, complications are common. The purposes of this study were to (1) evaluate the effect of an anatomic-specific titanium implant produced by 3-dimensional (3D) printing as a treatment option for recurrent shoulder instability with substantial glenoid bone loss and (2) compare the use of that implant with the Latarjet procedure. METHODS: Ten fresh-frozen cadaveric shoulders (mean age at the time of death, 78 years) were tested in a biomechanical setup with the humerus in 30° of abduction and in neutral rotation. The shoulders were tested under 5 different conditions: (1) normal situation, (2) creation of an anterior glenoid defect, (3) implantation of an anatomic-specific titanium implant produced by 3D printing, and the Latarjet procedure (4) with and (5) without 10 N of load attached to the conjoined tendon. In each condition, the humerus was translated 10 mm anteriorly relative to the glenoid, and the maximum peak translational force that was necessary for this translation was measured. RESULTS: After creation of the glenoid defect, the mean translational peak force decreased by 30% ± 6% compared with that for the normal shoulder. After restoration of the original glenoid anatomy, the translational force needed to dislocate the humeral head from the glenoid significantly increased compared with that in the defect condition-to 119% ± 16% of normal (p &lt; 0.01) with the 3D-printed anatomic-specific implant and to 121% ± 48% of normal (p &lt; 0.01) following the Latarjet procedure. No significant differences in mean translational force were found between the anatomic-specific implant and the Latarjet procedure (p = 0.72). CONCLUSIONS: The mean translational peak force needed to dislocate the humerus 10 mm anteriorly on the glenoid was higher after glenoid restoration with the 3D-printed anatomic-specific implant compared with when the glenoid had a 20% surface defect but also compared with when the glenoid was intact. No differences in mean translational peak force were found between the 3D-printed anatomic-specific glenoid implant and the Latarjet procedure, although there was less variability in the 3D-implant condition. CLINICAL RELEVANCE: Novel 3D-printing technology could provide a reliable patient-specific alternative to solve problems related to traditional treatment methods for shoulder instability.</p

Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

A case-cohort analysis of human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ≥ 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 205 individuals (24%). A persistently elevated CRP level but not an elevated CRP level only at a single time point was independently associated with increased clinical failure, compared with a persistently low CRP level, despite achievement of virologic suppression. Serial monitoring of CRP levels could identify individuals who are at highest risk of HIV progression and may benefit from future adjunct antiinflammatory therapies

Prevalence and risk factors of micronutrient deficiencies pre- and post-antiretroviral therapy (ART) among a diverse multicountry cohort of HIV-infected adults.

BACKGROUND & AIMS HIV-infected adults have increased risk of several individual micronutrient deficiencies. However, the prevalence and risk factors of concurrent and multiple micronutrient deficiencies and whether micronutrient concentrations change after antiretroviral therapy (ART) initiation have not been well described. The objective of this study was to determine the prevalence and risk factors of individual, concurrent and multiple micronutrient deficiencies among ART-naïve HIV-infected adults from nine countries and assess change in micronutrient status 48 weeks post-ART initiation. METHODS A random sub-cohort (n = 270) stratified by country was selected from the multinational PEARLS clinical trial (n = 1571 ART-naïve, HIV-infected adults). We measured serum concentrations of vitamins A, D (25-hydroxyvitamin), E, carotenoids and selenium pre-ART and 48 weeks post-ART initiation, and measured vitamins B6, B12, ferritin and soluble transferrin receptor at baseline only. Prevalence of single micronutrient deficiencies, concurrent (2 coexisting) or conditional (a deficiency in one micronutrient given a deficiency in another) and multiple (≥3) were determined using defined serum concentration cutoffs. We assessed mean changes in micronutrient concentrations from pre-ART to week 48 post-ART initiation using multivariable random effects models. RESULTS Of 270 participants, 13.9%, 29.2%, 24.5% and 32.4% had 0, 1, 2 and multiple deficiencies, respectively. Pre-ART prevalence was the highest for single deficiencies of selenium (53.2%), vitamin D (42.4%), and B6 (37.3%) with 12.1% having concurrent deficiencies of all three micronutrients. Deficiency prevalence varied widely by country. 48 weeks post-ART initiation, mean vitamin A concentration increased (p < 0.001) corresponding to a 9% decrease in deficiency. Mean concentrations also increased for other micronutrients assessed 48 weeks post-ART (p < 0.001) but with minimal change in deficiency status. CONCLUSIONS Single and multiple micronutrient deficiencies are common among HIV-infected adults pre-ART initiation but vary between countries. Importantly, despite increases in micronutrient concentrations, prevalence of individual deficiencies remains largely unchanged after 48 weeks on ART. Our results suggest that ART alone is not sufficient to improve micronutrient deficiency

Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study

NWCS 319 and PEARLS Study Team are part of the authors group.Submitted by Fábio Marques ([email protected]) on 2018-12-03T13:30:38Z No. of bitstreams: 1 Inflammation and micronutrient_Sandra_Cardoso_INI_Lapclin-AIDS_2018.pdf: 629473 bytes, checksum: b0b85635de76eec945b83a38f186ddb2 (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-12-05T16:06:59Z (GMT) No. of bitstreams: 1 Inflammation and micronutrient_Sandra_Cardoso_INI_Lapclin-AIDS_2018.pdf: 629473 bytes, checksum: b0b85635de76eec945b83a38f186ddb2 (MD5)Made available in DSpace on 2018-12-05T16:06:59Z (GMT). No. of bitstreams: 1 Inflammation and micronutrient_Sandra_Cardoso_INI_Lapclin-AIDS_2018.pdf: 629473 bytes, checksum: b0b85635de76eec945b83a38f186ddb2 (MD5) Previous issue date: 2018Johns Hopkins University. School of Medicine. Department of Medicine. Baltimore, MD, USA./ Columbia University Mailman School of Public Health. Department of Epidemiology. New York, NY, USA.Johns Hopkins University. School of Medicine. Department of Medicine. Baltimore, MD, USA.National AIDS Research Institute. Pune, India./ National Institute of Research in Tuberculosis. Chennai, India.YR Gaitonde Center for AIDS Research and Education. Chennai, India.UNC Lilongwe. Lilongwe, Malawi.Johns Hopkins University Research Project. Malawi College of Medicine. Blantyre, Malawi./ Liverpool School of Tropical Medicine. Liverpool, UK.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Hospital Nossa Senhora de Conceição. Porto Alegre, RS, Brasil.Asociacion Civil Impacta Salud y Educacion. Lima, Peru.University of Witwatersrand. Department of Medicine. Johannesburg, South Africa.Durban University of Technology. Durban International Clinical Research Site. Durban, South Africa.University of Zimbabwe. Clinical Research Centre. Harare, Zimbabwe.Les Centres GHESKIO. Port-Au-Prince, Haiti.Research Institute for Health Sciences. Chiang Mai, Thailand.Johns Hopkins University. School of Medicine. Department of Medicine. Baltimore, MD, USA./ Johns Hopkins Bloomberg School of Public Health. Department of International Health. Baltimore, MD, USA.Johns Hopkins University. School of Medicine. Department of Medicine. Baltimore, MD, USA.Johns Hopkins University. School of Medicine. Department of Ophthalmology. Baltimore, MD, USA.Johns Hopkins Bloomberg School of Public Health. Department of International Health. Baltimore, MD, USA./ Bill and Melinda Gates Foundation. Seattle, USA.University of Colorado. School of Medicine. Division of Infectious Diseases. Department of Medicine. Aurora, CO, USA.Johns Hopkins University. School of Medicine. Department of Medicine. Baltimore, MD, USA.Background: Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). Methods: Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). Results: In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17–1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26–0.87). Conclusion: Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation

Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort.

Background.  We assessed immune activation after antiretroviral therapy (ART) initiation to understand clinical failure in diverse settings. Methods.  We performed a case-control study in ACTG Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS). Cases were defined as incident World Health Organization Stage 3 or 4 human immunodeficiency virus (HIV) disease or death, analyzed from ART weeks 24 (ART24) to 96. Controls were randomly selected. Interleukin (IL)-6, interferon (IFN)-γ-inducible protein-10, IL-18, tumor necrosis factor-α, IFN-γ, and soluble CD14 (sCD14) were measured pre-ART and at ART24 in plasma. Continued elevation was defined by thresholds set by highest pre-ART quartiles (&gt;Q3). Incident risk ratios (IRRs) for clinical progression were estimated by Poisson regression, adjusting for age, sex, treatment, country, time-updated CD4+ T-cell count, HIV ribonucleic acid (RNA), and prevalent tuberculosis. Results.  Among 99 cases and 234 controls, median baseline CD4+ T-cell count was 181 cells/µL, and HIV RNA was 5.05 log10 cp/mL. Clinical failure was independently associated with continued elevations of IL-18 (IRR, 3.03; 95% confidence interval [CI], 1.27-7.20), sCD14 (IRR, 2.17; 95% CI, 1.02-4.62), and IFN-γ (IRR, 0.08; 95% CI, 0.01-0.61). Among 276 of 333 (83%) who were virologically suppressed at ART24, IFN-γ was associated with protection from failure, but the association with sCD14 was attenuated. Conclusions.  Continued IL-18 and sCD14 elevations were associated with clinical ART failure. Interferon-γ levels may reflect preserved immune function