Urinary naphthalene and phenanthrene as biomarkers of occupational exposure to polycyclic aromatic hydrocarbons.

OBJECTIVES: The study investigated the utility of unmetabolised naphthalene (Nap) and phenanthrene (Phe) in urine as surrogates for exposures to mixtures of polycyclic aromatic hydrocarbons (PAHs). METHODS: The report included workers exposed to diesel exhausts (low PAH exposure level, n = 39) as well as those exposed to emissions from asphalt (medium PAH exposure level, n = 26) and coke ovens (high PAH exposure level, n = 28). Levels of Nap and Phe were measured in urine from each subject using head space-solid phase microextraction and gas chromatography-mass spectrometry. Published levels of airborne Nap, Phe and other PAHs in the coke-producing and aluminium industries were also investigated. RESULTS: In post-shift urine, the highest estimated geometric mean concentrations of Nap and Phe were observed in coke-oven workers (Nap: 2490 ng/l; Phe: 975 ng/l), followed by asphalt workers (Nap: 71.5 ng/l; Phe: 54.3 ng/l), and by diesel-exposed workers (Nap: 17.7 ng/l; Phe: 3.60 ng/l). After subtracting logged background levels of Nap and Phe from the logged post-shift levels of these PAHs in urine, the resulting values (referred to as ln(adjNap) and ln(adjPhe), respectively) were significantly correlated in each group of workers (0.71 < or = Pearson r < or = 0.89), suggesting a common exposure source in each case. Surprisingly, multiple linear regression analysis of ln(adjNap) on ln(adjPhe) showed no significant effect of the source of exposure (coke ovens, asphalt and diesel exhaust) and further suggested that the ratio of urinary Nap/Phe (in natural scale) decreased with increasing exposure levels. These results were corroborated with published data for airborne Nap and Phe in the coke-producing and aluminium industries. The published air measurements also indicated that Nap and Phe levels were proportional to the levels of all combined PAHs in those industries. CONCLUSION: Levels of Nap and Phe in urine reflect airborne exposures to these compounds and are promising surrogates for occupational exposures to PAH mixtures

Fractionation of protein adducts in rats and mice dosed with C-14 pentachlorophenol

Pentachlorophenol (PCP) induces liver cancer in mice, possibly due to covalent binding of PCP metabolites to critical macromolecules. In this work, covalent binding was related to PCP biotransformation and specific (cysteinyl) adducts of chlorinated quinones in liver and blood of Sprague-Dawley rats and B6C3F1 mice dosed with [C-14]PCP. Using a sequential scheme of scintillation counting along with selective cleavage of cysteinyl adducts by Raney nickel, we quantified total radiobinding, total covalent binding, non-cysteinyl protein binding, and specific protein adducts in liver nuclei (Np), liver cytosol (Cp), hemoglobin (Hb), and serum albumin (Alb). Almost all of the radiobinding to Np (> 98%) was attributed to covalent binding in both rats and mice. Regarding Cp, more covalent binding was observed in mice than in rats (100% versus 67%, P = 0.015). Very little binding was attributed to serum Alb (rats 1.3%, mice 2.6%, P = 0.046) or Hb (not detected in either species). These results indicate that the liver was the main organ for PCP metabolism and that relatively little of the dose of reactive metabolites became systemically available. Cysteinyl binding accounted for 76-91% of total covalent binding to Np and 68-76% of total covalent binding to Cp. In addition, five times more PCP was bioactivated in the livers of mice than in those of rats (2.14% of the dose bound to Cp in mice and 0.416% in rats). These results reinforce previous studies, suggesting that the liver was a target organ of PCP carcinogenicity and that mice were more susceptible to liver damage than rats. However, the sum of all quantified adducts accounted for only 7-8% of total cysteinyl binding to Np and 2% to Cp, suggesting that other uncharacterized binding species may be important to the toxicity of PCP

Distributed GIS for automated natural hazard zonation mapping internet-SMS warning towards sustainable society

Today, open systems are needed for real time analysis and warnings on geo-hazards and over time can be achieved using Open Source Geographical Information System (GIS)-based platform such as GeoNode which is being contributed to by developers around the world. To develop on an open source platform is a very vital component for better disaster information management as far as spatial data infrastructures are concerned and this would be extremely vital when huge databases are to be created and consulted regularly for city planning at different scales, particularly satellite images and maps of locations. There is a big need for spatially referenced data creation, analysis, and management. Some of the salient points that this research would be able to definitely contribute with GeoNode, being an open source platform, are facilitating the creation, sharing, and collaborative use of geospatial data. The objective is development of an automated natural hazard zonation system with Internet-short message service (SMS) warning utilizing geomatics for sustainable societies. A concept of developing an internet-resident geospatial geohazard warning system has been put forward in this research, which can communicate alerts via SMS. There has been a need to develop an automated integrated system to categorize hazard and issue warning that reaches users directly. At present, no web-enabled warning system exists which can disseminate warning after hazard evaluation at one go and in real time. The objective of this research work has been to formalize a notion of an integrated, independent, generalized, and automated geo-hazard warning system making use of geo-spatial data under popular usage platform. In this paper, a model of an automated geo-spatial hazard warning system has been elaborated. The functionality is to be modular in architecture having GIS-graphical user interface (GUI), input, understanding, rainfall prediction, expert, output, and warning modules. A simplified but working prototype of the system without the GIS-GUI module has been already tested, validated, and reported. Through this paper, a significantly enhanced system integrated with web-enabled-geospatial information has been proposed, and it can be concluded that an automated hazard warning system has been conceptualized and researched. However, now the scope is to develop it further

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Biomonitoring exposure to styrene and styrene-(7,8)-oxide by repeated measurements

Aims: To investigat the use of urinary analytes and protein adducts as biomarkers of occupational exposure to airborne styrene (Sty) and styrene-(7,8)-oxide (StyOX) adopting a repeated measurements sampling design. Methods: Using this protocol (1 to 4 samplings), we sampled reinforced plastics workers (n=8), varnish workers (n=13), and control workers (n=22). Results: Median levels of personal exposure in these groups were 18.2, 3.4 and <0.3 mg/m3 for Sty and 133, 12 and <5 \ub5g/m3 for StyOX. Among the exposed workers, levels of Sty and StyOX were positively correlated (Pearson r=0.794). Levels of urinary styrene (StyU), mandelic acid (MA), phenylglyoxylic acid (PGA), phenylglycine (PHG), 4-vinylphenol (VP), and mercapturic acids (M1+M2), were significantly higher in exposed than in controls, and were positively correlated with both Sty and StyOX (r up to 0.974), and with each other. Although cysteinyl albumin and hemoglobin adducts of styrene-(7,8)-oxide adduct levels were consistently greater in exposed than in controls, the differences were not statistically significant. Levels of 2PE-albumin were negatively correlated with levels of M1+M2; suggesting a competition of glutathione and cysteinyl residues of albumin toward StyOX. A screening of effects on biomarker levels of job, smoking, and GST genotype showed that job was the major determinant, although GSTM1 polymorphism and cigarette smoking significantly influenced M1+M2 and VP, respectively. Multiple linear regression of the logged levels of urinary biomarkers vs. Sty and StyU (R2 up to 0.944) showed that values of \u3b2Sty were close to one for StyU, M1+M2, and MA, and significantly less than one for VP, indicating that the natural scale relationships would be concave downwards with increasing Sty; such behavior would suggest saturable metabolism of the pathways leading to VP. Conclusion: The repeated measurements sampling design strengths the relationship between biomarkers and exposure and together with the use of several biomarkers greatly improve our capability to investigate metabolism of Sty and StyOx in humans