God, Gaia, the Taxpayer and the Lorax: Standing, Justiciability, and Separation of Powers after Massachusetts and Hein

The Supreme Court decided two important standing cases during the October 2006 term: Hein v. Freedom from Religion Foundation and Massachusetts v. EPA. The latter is important for what it did, the former for what it did not do. Whereas Hein hewed closely - perhaps too closely - to prior standing precendents, the Massachusetts decision substantially departed from existing precedent and established a new doctrine of special solicitude to state standing. Both decisions involved generalized grievances about federal government policies that affect citizens as a whole, but point in opposite directions. In many respects the opinions are in significant tension with each other, and embrace competing conceptions of the role of the judiciary in the separation of powers. What neither decision did, however, is etch a conservative imprint on the law of standing. This article is based upon remarks delivered at the Regent University Law Review symposium, Justiciability After Hein and Massachusetts: Where Is the Court Standing? Nov. 30, 2007

Inhaled Sedation in Patients with COVID-19-Related Acute Respiratory Distress Syndrome: An International Retrospective Study

Background and objectives: The coronavirus disease 2019 (COVID-19) pandemic and the shortage of intravenous sedatives has led to renewed interest in inhaled sedation for patients with acute respiratory distress syndrome (ARDS). We hypothesized that inhaled sedation would be associated with improved clinical outcomes in COVID-19 ARDS patients. Methods: Retrospective international study including mechanically ventilated patients with COVID-19 ARDS who required sedation and were admitted to 10 European and US intensive care units. The primary endpoint of ventilator-free days through day 28 was analyzed using zero-inflated negative binomial regression, before and after adjustment for site, clinically relevant covariates determined according to the univariate results, and propensity score matching. Results: A total of 196 patients were enrolled, 78 of whom died within 28 days. The number of ventilator-free days through day 28 did not differ significantly between the patients who received inhaled sedation for at least 24 h (n = 111) and those who received intravenous sedation only (n = 85), with medians of 0 (interquartile range [IQR] 0–8) and 0 (IQR 0–17), respectively (odds ratio for having zero ventilator-free days through day 28, 1.63, 95% confidence interval [CI], 0.91–2.92, p = 0.10). The incidence rate ratio for the number of ventilator-free days through day 28 if not 0 was 1.13 (95% CI, 0.84–1.52, p = 0.40). Similar results were found after multivariable adjustment and propensity matching. Conclusion: The use of inhaled sedation in COVID-19 ARDS was not associated with the number of ventilator-free days through day 28. Keywords: coronavirus disease 2019; acute respiratory distress syndrome; inhaled sedation; sevoflurane; isofluran

Comparison of five D-dimer reagents and application of an age-adjusted cut-off for the diagnosis of venous thromboembolism in emergency department

There is still a considerable uncertainty concerning D-dimer cut-off values used in exclusion of venous thromboembolic (venous thromboembolism, VTE) disease, especially among the elderly patients. The objectives were to compare five different D-dimer reagents in the daily practice of an emergency department and to test retrospectively the performances of an age-adjusted cut-off. A total of 473 consecutive ambulatory outpatients suspected of VTE (confirmed VTE = 21) were included in this study. Five commercially available tests were assessed: STA-Liatest D-Di (LI), AxSYMD-Dimer (AX), VIDAS D-Dimer (VI), INNOVANCE D-Dimer (IN), and HemosIL D-Dimer HS (HS). When using a cut-off value of 500 ng/ml fibrinogen equivalent units (FEUs), D-dimer reagents differ in their abilities to avoid further testing. Indeed, LI allowed exclusion of VTE diagnosis in statistically more patients than VI, AX, and IN but not HS. The use of an age-adjusted cut-off is cost-effective without increasing significantly the number of false negative results. The interest of such strategy is more or less pronounced, depending on the type of D-dimer reagent. The application of an age-adjusted cut-off may be useful to reduce differences among D-dimer reagents to lower costly imaging studies. Prospective validation studies on large cohorts of patients are required to determine the safety of such strategy

Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells

BACKGROUND: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells. METHODS: Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12 months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells. RESULTS: We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development. CONCLUSIONS: Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer

Health-related quality of life of food-allergic children compared with healthy controls and other diseases

Background Food allergy is a potentially life-threatening disease, affecting up to 10% of the pediatric population. Objective The aim of our study was to assess the health-related quality of life (HRQL) of food-allergic patients compared with the general population and patients with other chronic diseases with dietary or allergic burden, in a cross-sectional study. Methods We recruited patients aged 8-17 years diagnosed with food allergy and matched healthy controls recruited in schools. We also included patients with asthma, inflammatory bowel disease, celiac disease, diabetes, obesity, and eating disorders. We used the CHQ-CF87 questionnaire for generic HRQL assessment. Food allergy HRQL was also assessed using specific questionnaires: Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM). Results One hundred and thirty-five food-allergic children, 255 children with chronic diseases, and 463 healthy controls were included in the analyses. Food-allergic patients had a better HRQL than healthy controls in the Behavior (BE), Bodily Pain (BP), Family Activities (FA), and Mental Health (MH) domains and a worse HRQL in the General Health Perception (GH) domain (p = .048). Food-allergic patients exhibited a better HRQL than patients affected by other chronic diseases, notably diabetes. Although an epinephrine autoinjector had been prescribed to 87.4% of the food-allergic children, only 54.2% of them carried it at all times. Conclusion Food-allergic patients display overall good HRQL compared with the general population and those with other diseases with daily symptoms and treatments, in line with recent improvements in food allergy management

Impact of Zika Virus Emergence in French Guiana: A Large General Population Seroprevalence Survey.

BACKGROUND: Since the identification of Zika virus (ZIKV) in Brazil in May 2015, the virus has spread throughout the Americas. However, ZIKV burden in the general population in affected countries remains unknown. METHODS: We conducted a general population survey in the different communities of French Guiana through individual interviews and serologic survey during June-October 2017. All serum samples were tested for anti-ZIKV immunoglobulin G antibodies using a recombinant antigen-based SGERPAxMap microsphere immunoassay, and some of them were further evaluated through anti-ZIKV microneutralization tests. RESULTS: The overall seroprevalence was estimated at 23.3% (95% confidence interval [CI], 20.9%-25.9%) among 2697 participants, varying from 0% to 45.6% according to municipalities. ZIKV circulated in a large majority of French Guiana but not in the most isolated forest areas. The proportion of reported symptomatic Zika infection was estimated at 25.5% (95% CI, 20.3%-31.4%) in individuals who tested positive for ZIKV. CONCLUSIONS: This study described a large-scale representative ZIKV seroprevalence study in South America from the recent 2015-2016 Zika epidemic. Our findings reveal that the majority of the population remains susceptible to ZIKV, which could potentially allow future reintroductions of the virus

Spatial Distribution and Burden of Emerging Arboviruses in French Guiana.

Despite the health, social and economic impact of arboviruses in French Guiana, very little is known about the extent to which infection burden is shared between individuals. We conducted a large multiplexed serological survey among 2697 individuals from June to October 2017. All serum samples were tested for IgG antibodies against DENV, CHIKV, ZIKV and MAYV using a recombinant antigen-based microsphere immunoassay with a subset further evaluated through anti-ZIKV microneutralization tests. The overall DENV seroprevalence was estimated at 73.1% (70.6-75.4) in the whole territory with estimations by serotype at 68.9% for DENV-1, 38.8% for DENV-2, 42.3% for DENV-3, and 56.1% for DENV-4. The overall seroprevalence of CHIKV, ZIKV and MAYV antibodies was 20.3% (17.7-23.1), 23.3% (20.9-25.9) and 3.3% (2.7-4.1), respectively. We provide a consistent overview of the burden of emerging arboviruses in French Guiana, with useful findings for risk mapping, future prevention and control programs. The majority of the population remains susceptible to CHIKV and ZIKV, which could potentially facilitate the risk of further re-emergences. Our results underscore the need to strengthen MAYV surveillance in order to rapidly detect any substantial changes in MAYV circulation patterns

A single tRNA base pair mediates bacterial tRNA-dependent biosynthesis of asparagine

In many prokaryotes and in organelles asparagine and glutamine are formed by a tRNA-dependent amidotransferase (AdT) that catalyzes amidation of aspartate and glutamate, respectively, mischarged on tRNA(Asn) and tRNA(Gln). These pathways supply the deficiency of the organism in asparaginyl- and glutaminyl-tRNA synthtetases and provide the translational machinery with Asn-tRNA(Asn) and Gln-tRNA(Gln). So far, nothing is known about the structural elements that confer to tRNA the role of a specific cofactor in the formation of the cognate amino acid. We show herein, using aspartylated tRNA(Asn) and tRNA(Asp) variants, that amidation of Asp acylating tRNA(Asn) is promoted by the base pair U(1)–A(72) whereas the G(1)–C(72) pair and presence of the supernumerary nucleotide U(20A) in the D-loop of tRNA(Asp) prevent amidation. We predict, based on comparison of tRNA(Gln) and tRNA(Glu) sequence alignments from bacteria using the AdT-dependent pathway to form Gln-tRNA(Gln), that the same combination of nucleotides also rules specific tRNA-dependent formation of Gln. In contrast, we show that the tRNA-dependent conversion of Asp into Asn by archaeal AdT is mainly mediated by nucleotides G(46) and U(47) of the variable region. In the light of these results we propose that bacterial and archaeal AdTs use kingdom-specific signals to catalyze the tRNA-dependent formations of Asn and Gln

Seroprevalence of anti-SARS-CoV-2 IgG at the first epidemic peak in French Guiana, July 2020.

Funder: National Research AgencyFunder: Regional Health Agency of French GuianaFunder: Institut Pasteur Urgence COVID-19 fundraisingBACKGROUND: While Latin America has been heavily affected by the pandemic, only a few seroprevalence studies have been conducted there during the first epidemic wave in the first half of 2020. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was performed between 15 July 2020 and 23 July 2020 among individuals who visited 4 medical laboratories or 5 health centers for routine screening or clinical management, with the exception of symptomatic suggestive cases of covid-19. Samples were screened for the presence of anti-SARS-CoV-2 IgG directed against domain S1 of the SARS-CoV-2 spike protein using the anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from Euroimmun. CONCLUSIONS/SIGNIFICANCE: The overall seroprevalence was 15.4% [9.3%-24.4%] among 480 participants, ranging from 4.0% to 25.5% across the different municipalities. The seroprevalence did not differ according to gender (p = 0.19) or age (p = 0.51). Among SARS-CoV-2 positive individuals, we found that 24.6% [11.5%-45.2%] reported symptoms consistent with COVID-19. Our findings revealed high levels of infection across the territory but a low number of resulting deaths, which can be explained by French Guiana's young population structure

Reconstructing Mayaro virus circulation in French Guiana shows frequent spillovers

Funder: This study was supported by the “European Regional Development Fund” under EPI-ARBO grant agreement (GY0008695), the “Regional Health Agency of French Guiana”, the “National Center of Spatial Studies”. CF acknowledges funding from Calmette and Yersin allocated by the “Pasteur Institut Department of International Affairs”. N.H. and S.C. acknowledge financial support from the AXA Research Fund, the Investissement d’Avenir program, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases program (Grant ANR-10-LABX-62-IBEID), the Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, the INCEPTION project (PIA/ANR-16-CONV-0005), the European Union’s Horizon 2020 research and innovation programme under ZIKAlliance grant agreement No 734548.Abstract: Characterizing the circulation of Mayaro virus (MAYV), an emerging arbovirus threat, is essential for risk assessment but challenging due to cross-reactivity with other alphaviruses such as chikungunya virus (CHIKV). Here, we develop an analytical framework to jointly assess MAYV epidemiology and the extent of cross-reactivity with CHIKV from serological data collected throughout French Guiana (N = 2697). We find strong evidence of an important sylvatic cycle for MAYV with most infections occurring near the natural reservoir in rural areas and in individuals more likely to go to the forest (i.e., adult males) and with seroprevalences of up to 18% in some areas. These findings highlight the need to strengthen MAYV surveillance in the region and showcase how modeling can improve interpretation of cross-reacting assays