Ascorbic acid supplementation does not lower plasma lipoprotein(a) concentrations

Abstract Elevated plasma concentrations of lipoprotein(a) (Lp[a]) are associated with premature coronary heart disease (CHD). Lp(a) is a lipoprotein particle consisting of low-density lipoprotein (LDL) with apolipoprotein (apo) (a) attached to the apo B-100 component of LDL. It has been hypothesized that ascorbic acid supplementation may reduce plasma levels of Lp(a). The purpose of this study was to determine whether ascorbic acid supplementation at a dose of 1 g/day would lower plasma concentrations of Lp(a) when studied in a randomized, placebo-controlled, blinded fashion. One hundred and one healthy men and women ranging in age from 20 to 69 years were studied for 8 months. Lp(a) values at baseline for the placebo group (n= 52) and the ascorbic acid supplemented group (n= 49) were 0.026 and 0.033 g/l, respectively. The 8-month concentrations were 0.027 g/l (placebo) and 0.038 g/l (supplemented group). None of these values were significantly different from each other. In addition, no difference in plasma Lp(a) concentration was seen between the placebo and supplemented groups when only subjects with an initial Lp(a) value of ]0.050 g/l were analyzed. Our data indicate that plasma Lp(a) concentrations are not significantly affected by ascorbic acid supplementation in healthy human subjects

Observing the prompt emission of gamma-ray bursts

Gamma-ray bursts (GRBs) were first detected thanks to their prompt emission, which was the only information available for decades. In 2010, while the high-energy prompt emission remains the main tool for the detection and the first localization of GRB sources, our understanding of this crucial phase of GRBs has made great progress. We discuss some recent advances in this field, like the occasional detection of the prompt emission at all wavelengths, from optical to GeV; the existence of sub-luminous GRBs; the attempts to standardize GRBs; and the possible detection of polarization in two very bright GRBs. Despite these advances, tantalizing observational and theoretical challenges still exist, concerning the detection of the faintest GRBs, the panchromatic observation of GRBs from their very beginning, the origin of the prompt emission, or the understanding of the physics at work during this phase. Significant progress on this last topic is expected with SVOM thanks to the observation of dozens of GRBs from optical to MeV during the burst itself, and the measure of the redshift for the majority of them. SVOM will also change our view of the prompt GRB phase in another way. Within a few years, the sensitivity of sky surveys at optical and radio frequencies, and outside the electromagnetic domain in gravitational waves or neutrinos, will allow them to detect several new types of transient signals, and SVOM will be uniquely suited to identify which of these transients are associated with GRBs. This radically novel look at GRBs may elucidate the complex physics producing these bright flashes.Comment: To appear in a special issue of Comptes Rendus Physique "GRB studies in the SVOM era", Eds. F. Daigne, G. Dubus. 15 pages 9 figure

Follow-up after radiological intervention in oncology: ECIO-ESOI evidence and consensus-based recommendations for clinical practice

Interventional radiology plays an important and increasing role in cancer treatment. Follow-up is important to be able to assess treatment success and detect locoregional and distant recurrence and recommendations for follow-up are needed. At ECIO 2018, a joint ECIO-ESOI session was organized to establish follow-up recommendations for oncologic intervention in liver, renal, and lung cancer. Treatments included thermal ablation, TACE, and TARE. In total five topics were evaluated: ablation in colorectal liver metastases (CRLM), TARE in CRLM, TACE and TARE in HCC, ablation in renal cancer, and ablation in lung cancer. Evaluated modalities were FDG-PET-CT, CT, MRI, and (contrast-enhanced) ultrasound. Prior to the session, five experts were selected and performed a systematic review and presented statements, which were voted on in a telephone conference prior to the meeting by all panelists. These statements were presented and discussed at the ECIO-ESOI session at ECIO 2018. This paper presents the recommendations that followed from these initiatives. Based on expert opinions and the available evidence, follow-up schedules were proposed for liver cancer, renal cancer, and lung cancer. FDG-PET-CT, CT, and MRI are the recommended modalities, but one should beware of false-positive signs of residual tumor or recurrence due to inflammation early after the intervention. There is a need for prospective preferably multicenter studies to validate new techniques and new response criteria. This paper presents recommendations that can be used in clinical practice to perform the follow-up of patients with liver, lung, and renal cancer who were treated with interventional locoregional therapies

Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data

BACKGROUND: Previous WHO guidance on tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards, which might represent barriers to PrEP implementation and uptake. We aimed to systematically review published literature on kidney toxicity among tenofovir disoproxil fumarate-based oral PrEP users and conducted an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset. METHODS: In this systematic review and meta-analysis we searched PubMed up to June 30, 2021, for randomised controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (tenofovir disoproxil fumarate-based PrEP alone or in combination with emtricitabine or lamivudine). We extracted summary data and conducted meta-analyses with random-effects models to estimate relative risks of grade 1 and higher and grade 2 and higher kidney-related adverse events, measured by elevated serum creatinine or decline in estimated creatinine clearance or estimated glomerular filtration rate. The IPDMA included (largely unpublished) individual participant data from 17 PrEP implementation projects and two RCTs. Estimated baseline creatinine clearance and creatinine clearance change after initiation were described by age, gender, and comorbidities. We used random-effects regressions to estimate the risk in decline of creatinine clearance to less than 60 mL/min. FINDINGS: We identified 62 unique records and included 17 articles reporting on 11 RCTs with 13 523 participants in meta-analyses. PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio [OR] 1·49, 95% CI 1·22-1·81; I2=25%) and grade 2 and higher events (OR 1·75, 0·68-4·49; I2=0%), although the grade 2 and higher association was not statistically significant and events were rare (13 out of 6764 in the intervention group vs six out of 6782 in the control group). The IPDMA included 18 676 individuals from 15 countries (1453 [7·8%] from RCTs) and 79 (0·42%) had a baseline estimated creatinine clearance of less than 60 mL/min (increasing proportions with increasing age). Longitudinal analyses included 14 368 PrEP users and 349 (2·43%) individuals had a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and baseline creatinine clearance of 60·00-89·99 mL/min (adjusted hazard ratio [aHR] 8·49, 95% CI 6·44-11·20) and less than 60 mL/min (aHR 20·83, 12·83-33·82). INTERPRETATION: RCTs suggest that risks of kidney-related adverse events among tenofovir disoproxil fumarate-based oral PrEP users are increased but generally mild and small. Our global PrEP user analysis found varying risks by age and baseline creatinine clearance. Kidney function screening and monitoring might focus on older individuals, those with baseline creatinine clearance of less than 90 mL/min, and those with kidney-related comorbidities. Less frequent or optional screening among younger individuals without kidney-related comorbidities may reduce barriers to PrEP implementation and use. FUNDING: Unitaid, Bill & Melinda Gates Foundation, WHO

Demonstration of a Heterogeneous Satellite Architecture During RIMPAC 2018

The Micro-Satellite Military Utility (MSMU) Project Arrangement (PA) is an agreement under the Responsive Space Capabilities (RSC) Memorandum of Understanding (MOU) involving the Departments and Ministries of Defence of Australia, Canada, Germany, Italy, Netherlands, New Zealand, Norway, United Kingdom and United States. MSMU’s charter is to inform a space enterprise that provides military users with reliable access to a broad spectrum of information in an opportunistic environment. The MSMU community participated on a non-interference basis in the biennial Rim of the Pacific (RIMPAC) exercise from 26 June to 2 August 2018. This provided an opportunity to explore the military utility of a heterogeneous space architecture of satellites including traditional government and commercial satellites, as well as micro-satellites and nanosatellites associated with the “new space” paradigm. The objective was to test the hypothesis that a heterogeneous space architecture, mostly composed of small satellites, can bring significant value to the operational theatre. This paper describes the results from the MSMU experiment, outlines the lessons learned in terms of the infrastructure required to support such an experiment, and offers insights into the military utility of the heterogeneous space architecture. It concludes that a cooperative heterogeneous space architecture does have advantages and value, and that micro-satellites and nanosatellites contribute significant capability

The above L-band and P-band airborne synthetic aperture radar surveys

Permafrost-affected ecosystems of the Arctic-boreal zone in northwestern North America are undergoing profound transformation due to rapid climate change. NASA\u27s Arctic Boreal Vulnerability Experiment (ABoVE) is investigating characteristics that make these ecosystems vulnerable or resilient to this change. ABoVE employs airborne synthetic aperture radar (SAR) as a powerful tool to characterize tundra, taiga, peatlands, and fens. Here, we present an annotated guide to the L-band and P-band airborne SAR data acquired during the 2017, 2018, 2019, and 2022 ABoVE airborne campaigns. We summarize the g 1/480 SAR flight lines and how they fit into the ABoVE experimental design (Miller et al., 2023; https://doi.org/10.3334/ORNLDAAC/2150). The Supplement provides hyperlinks to extensive maps, tables, and every flight plan as well as individual flight lines. We illustrate the interdisciplinary nature of airborne SAR data with examples of preliminary results from ABoVE studies including boreal forest canopy structure from TomoSAR data over Delta Junction, AK, and the Boreal Ecosystem Research and Monitoring Sites (BERMS) area in northern Saskatchewan and active layer thickness and soil moisture data product validation. This paper is presented as a guide to enable interested readers to fully explore the ABoVE L- and P-band airborne SAR data (https://uavsar.jpl.nasa.gov/cgi-bin/data.pl)

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Association Between Race/Ethnicity and COVID-19 Outcomes in Systemic Lupus Erythematosus Patients From the United States: Data From the COVID-19 Global Rheumatology Alliance

OBJECTIVE: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE). METHODS: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders. RESULTS: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36–5.53]) and Hispanic (OR 2.76 [95% CI 1.34–5.69]) individuals had higher odds of more severe outcomes than White individuals. CONCLUSION: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population