Ways to Improve the Diagnosis of Growth Hormone Deficiency

Developmen

Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on-going viral transcription

Introduction: Viral remission after analytical treatment interruption (ATI), termed post-treatment control, has been described in a small proportion of HIV-positive patients. This phenomenon has been separately associated to both low levels of HIV-1 proviral DNA as well as cell-associated RNA. We investigated whether the combination of both parameters could help predict delayed viral rebound after treatment interruption (TI). Methods: We conducted an open single-arm ATI study in four Belgian HIV reference centres from January 2016 to July 2018. Eligible participants were adults who had fewer than 50 HIV-1 RNA copies/mL for more than two years, more than 500 CD4 cells/mu L for more than three months, and were in general good health. Consenting participants who had fewer than 66 copies total HIV-1 DNA (t-DNA) and fewer than 10 copies cell-associated HIV-1 unspliced RNA (US-RNA) per million peripheral blood mononuclear cells (PBMCs), interrupted therapy and were monitored closely. Antiretroviral therapy (ART) was resumed after two consecutive viral loads exceeding 1000 copies or one exceeding 10,000 copies/mL. The primary outcome was the proportion of participants with fewer than 50 HIV-1 RNA copies/mL 48 weeks after TI. Secondary outcomes were time to viral rebound, the frequency of serious adverse events (AEs) and evolution of t-DNA and US-RNA after TI. Results: All 16 consenting participants who interrupted therapy experienced rapid viral rebound two to eight weeks after TI. No serious AEs were observed. Levels of t-DNA and US-RNA increased after TI but returned to pre-ATI levels after treatment restart. None of the studied demographic, clinical and biological parameters were predictive of time of viral rebound. Conclusions: The combination of low levels of t-DNA and US-RNA in PBMCs, corresponding respectively to a small and transcriptionally silent viral reservoir, is not predictive of viral remission after TI in patients on ART

Humoral and cellular immunogenicity, effectiveness and safety of COVID-19 mRNA vaccination in patients with pediatric rheumatic diseases: A prospective cohort study

OBJECTIVES: To evaluate immunogenicity, effectiveness and safety of COVID-19 vaccination in patients with pediatric autoimmune inflammatory rheumatic disease (pedAIIRD). METHODS: A prospective cohort study was performed at the pediatric rheumatology department of the Wilhelmina Children's Hospital in Utrecht, the Netherlands. Vaccination dates, COVID-19 cases and vaccine-related adverse events (AEs) were registered for all pedAIIRD patients during regular clinic visits from March 2021 - August 2022. SARS-CoV-2 IgG antibody levels and T-cell responses were measured from serum samples after vaccination, and clinical and drug therapy data were collected from electronic medical records. Rate of COVID-19 disease was compared between vaccinated and unvaccinated patients in a time-varying Cox regression analysis. RESULTS: A total of 157 patients were included in this study and 88 % had juvenile idiopathic arthritis (JIA). One hundred thirty-seven patients were fully vaccinated, of which 47 % used biological agents at the time of vaccination, and 20 patients were unvaccinated. Geometric mean concentrations (GMCs) of post-vaccine antibody levels against SARS-CoV-2 were above the threshold for positivity in patients who did and did not use biological agents at the time of vaccination, although biological users demonstrated significantly lower antibody levels (adjusted GMC ratio: 0.38, 95 % CI: 0.21 - 0.70). T-cell responses were adequate in all but two patients (9 %). The adjusted rate of reported COVID-19 was significantly lower for fully vaccinated patients compared to non-vaccinated patients (HR: 0.53, 95 % CI: 0.29 - 0.97). JIA disease activity scores were not significantly different after vaccination, and no serious AEs were reported. CONCLUSIONS: COVID-19 mRNA vaccines were immunogenic (both cellular and humoral), effective and safe in a large cohort of pedAIIRD patients despite their use of immunosuppressive medication

ARE Update Volume 11, Number 5

What is the Price of Oil?Farmland Conversion in California: Evidence from the Williamson Act ProgramCalifornia’s Water Problems: Why a Comprehensive Solution Makes Sens

ARE Update Volume 11, Number 5

What is the Price of Oil?Farmland Conversion in California: Evidence from the Williamson Act ProgramCalifornia’s Water Problems: Why a Comprehensive Solution Makes Sens

ACT on RE+FLEX: Accelerating Coal Transition Through Repurposing Coal Plants Into Renewable and Flexibility Centers

Decarbonizing the power sector forms a critical part of the global combat against climate change. This requires inter alia retirement of the global coal power plant fleet of 2,100 GW. Although a significant part of this capacity is aging, there are complex issues that need to be addressed including the economic viability of existing coal plants in some countries relative to renewable projects and barriers to exit of coal. We have used detailed power plant level operational cost data for ten developing countries with significant share of coal and compared these with levelized cost of renewables, to demonstrate that competitiveness of coal varies significantly across different geographies. Countries like India where renewable projects have been highly competitive and there is an aging fleet of coal plants many of which are far away from mines, are already highly uncompetitive. On the other hand, countries like South Africa that have relatively inexpensive coal plants, but the average cost of renewable projects have not yet dropped sufficiently (as of 2020), will require special efforts to phase out coal completely beyond plants that have reached, or gone well past their technical life. Accelerated retirement of coal would require a new business model that allows repurposing some of these sites for alternative usage including generation from renewables, conversion of the incumbent generator into a synchronous condenser coupled with a fly wheel to provide reactive power and inertia; and installation of energy storage systems. As a repurposed coal plant for energy related activities can retain part of the workforce, it can also address some of the complex social issues. In order to develop a comprehensive repurposing program at a national level, the process needs to follow a least-cost planning methodology to identify prospective coal plant candidates for repurposing and then undertake a cost-benefit analysis of individual projects. We have demonstrated this methodology using a case study for Morocco

Analytical treatment interruption (ATI) in patients with very small HIV reservoir

C

Qualitative plasma viral load determination as a tool for screening of viral reservoir size in PWH

Objective(s): Suppression of viral replication in patients on antiretroviral therapy (ART) is determined by plasma viral load (pVL) measurement. Whenever pVL reaches values below the limit of quantification, the qualitative parameter 'target detected' or 'target not detected' is available but often not reported to the clinician. We investigated whether qualitative pVL measurements can be used to estimate the viral reservoir size. Design: The study recruited 114 people with HIV (PWH) who are stable on ART between 2016 and 2018. The percentage of pVL measurements qualitatively reported as 'target detected' (PTD) within a 2-year period was calculated. Methods: t-DNA and US-RNA were used to estimate viral reservoir size and were quantified on peripheral blood mononuclear cells (PBMCs) using droplet digital PCR. Results: A median of 6.5 pVL measurements over a 2-year period was evaluated for each participant to calculate PTD. A positive correlation was found between t-DNA and PTD (r = 0.24; P = 0.011) but not between US-RNA and PTD (r = 0.1; P = 0.3). A significantly lower PTD was observed in PWH with a small viral reservoir, as estimated by t-DNA less than 66 copies/10(6) PBMCs and US-RNA less than 10 copies/10(6) PBMCs, compared with PWH with a larger viral reservoir (P = 0.001). We also show that t-DNA is detectable whenever PTD is higher than 56% and that ART regimen does not affect PTD. Conclusion: Our study shows that PTD provides an efficient parameter to preselect participants with a small viral reservoir based on already available pVL data for future HIV cure trials