Microbial activity affects sulphur in biogenic aragonite

Carbonates that exhibit obvious diagenetic alteration are usually excluded as archives in palaeoenvironmental studies. However, the potential impact of microbial alteration during early diagenesis is still poorly explored. To investigate the sensitivity of sulphur concentration, distribution, oxidation state and isotopic composition in marine aragonite to microbial alteration, Arctica islandica bivalves and Porites sp. corals were experimentally exposed to anaerobic microbial activity. The anoxic incubation media included a benthic bacterial strain Shewanella sediminis and a natural anoxic sediment slurry with a natural microbial community of unknown species. Combined fluorescence microscopy and synchrotron‐based analysis of the sulphur distribution and oxidation state enabled a comparison of organic matter and sulphur content in the two materials. Results revealed a higher proportion of reduced sulphur species and locally stronger fluorescence within the pristine bivalve shell compared to the pristine coral skeleton. Within the pristine bivalve specimen, reduced sulphur was enriched in layers along the inner shell margin. After incubation in the anoxic sediment slurry, this region revealed rust‐brown staining and a patchy S2‐ distribution pattern rather than S2‐‐layers. Another effect on sulphur distribution was rust‐brown coloured fibres along one growth line, revealing a locally higher proportion of sulphur. The δ34S value of carbonate‐associated sulphate remained largely unaffected by both incubation media, but a lower δ34S value of water‐soluble sulphate reflected the degradation of insoluble organic matter by microbes in both experiments. No significant alteration was detected in the coral samples exposed to microbial alteration. The data clearly identified a distinct sensitivity of organically bound sulphur in biogenic aragonite to microbial alteration even when “traditional” geochemical proxies such as δ18OCARB or δ13CCARB in the carbonate didn’t show any effect. Differences in the intensity of microbial alteration documented are likely due to inherent variations in the concentration and nature of original organic compositions in the samples

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation

Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO2/FiO2 ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival

Bulk Carbonate Sulfur Isotopic Composition of Carbonate Associated Sulfate in Squeeze Cake Residues from IODP Site U1553 on the southern Campbell Plateau

Carbonate associated sulfate sulfur isotope results from IODP Site U1553 (166°11.4801′E, 52°13.4294′S) located on the Campbell Plateau are presented. Pore water and bulk carbonate samples collected during IODP Expedition 378 at Site U1553 in January 2020 were used for this study. The sediment samples were prepared using a 4-day digestion outlined in Wotte et al., 2012 which sequentially removed the water-soluble sulfate until only the carbonate associated sulfate (CAS) remained in the sediment. The CAS was extracted using a 10% HCl solution and then precipitated out of solution by adding 10% BaCl2 to precipitate the CAS as barite. Sulfur isotopes in from the CAS samples were analyzed using an EA-Isolink elemental analyzer connected in continuous flow to a MAT253 IRMS and the oxygen isotopes in dissolved sulfate were measured using a thermal conversion elemental analyzer connected in continuous flow to a Delta V IRMS. Analytical precision was measured using repeated measurements of a blind standard with an average 2-sigma of 0.4‰ for sulfur isotopes (IAEA-SO-5). These data were collected to examine the impact of a long-duration (~26-million-year) unconformity has on the fidelity of the carbonate geochemical archive

Sulfur and Oxygen Isotopic Composition of Dissolved Sulfate in Interstitial Water Sample Residues from IODP Site U1553 on the southern Campbell Plateau

Dissolved sulfate sulfur and oxygen isotope results and carbonate associated sulfate sulfur isotope results from IODP Site U1553 (166°11.4801′E, 52°13.4294′S) located on the Campbell Plateau are presented. Pore water collected during IODP Expedition 378 at Site U1553 in January 2020 were used for this study. These samples were processed using a procedure modified from that in Wotte et al. (2012, doi:10.1016/j.gca.2012.02.013) to extract the sulfate from the aqueous phase. The dissolved sulfate in the pore water was extracted by first adding 10% HCl to acidify the pore water, then the sulfate was removed from solution as barium sulfate using a 10% BaCl2 solution. Sulfur isotopes in dissolved sulfate were analyzed using an EA-Isolink elemental analyzer connected in continuous flow to a MAT253 IRMS and the oxygen isotopes in dissolved sulfate were measured using a thermal conversion elemental analyzer connected in continuous flow to a Delta V IRMS. Analytical precision was measured using repeated measurements of a blind standard with an average 2-sigma of 0.4‰ for sulfur isotopes (IAEA-SO-5) and 0.3‰ for oxygen isotopes (NBS-127). These data were collected to examine the impact of a long-duration (~26-million-year) unconformity has on the fidelity of the carbonate geochemical archive

The Relationship between Bacterial Sulfur Cycling and Ca/Mg Carbonate Precipitation : Old Tales and New Insights from Lagoa Vermelha and Brejo do Espinho, Brazil

Over the few past decades, the concept of microbial sulfur cycling catalyzing the precipitation of CaMg (CO3)2 at low temperatures (&lt;40 °C) has been studied intensely. In this respect, two hypersaline lagoons, Lagoa Vermelha and Brejo do Espinho, in Brazil, have been the subject of numerous studies investigating sedimentary Ca/Mg carbonate formation. Here, we present the sulfur and oxygen isotopic compositions of dissolved sulfate from surface water, as well as sulfate and sulfide from pore-water (δ34SSO4, δ18OSO4, and δ34SH2S), the sulfur isotopic composition of sedimentary pyrite (δ34SCRS), and sulfur and oxygen isotopic compositions of carbonate-associated sulfate (CAS, δ34SCAS and δ18OCAS). The pore-water profiles at Lagoa Vermelha indicate ongoing bacterial sulfate reduction by increasing δ34SSO4, δ18OSO4 and δ34SCRS values downcore. At Brejo do Espinho, the pore-water profiles displayed no depth-dependent isotope trends; the Ca/Mg ratio was, on average, lower, and the δ18OSO4 values in both surface and pore-water were strongly enriched in 18O. There was an overall mismatch between δ34SSO4 and the significantly higher δ34SCAS values. A negative correlation was observed between the Ca/Mg ratio and higher δ34SCAS values. The results show that the size difference between the two lagoons induces differences in the intensity of evaporation, which leads to the increased secretion of extrapolymeric substances (EPSs) by microbes in the smaller Brejo do Espinho. EPS provides the microenvironment where Ca/Mg carbonate can nucleate and preserve increased δ34SCAS values. Apart from EPS, increased sulfur oxidation is proposed to be a second factor causing relative enrichment of Ca/Mg carbonates at Brejo do Espinho. Our results emphasize the role of evaporative processes on Ca/Mg carbonate formation, and indicate that the respective δ34SCAS values reflect microenvironments rather than preserving an open marine δ34SSO4 signature

Anaerobic microbial activity affects earliest diagenetic pathways of bivalve shells

The earliest diagenetic post-mortem exposure of biogenic carbonates at the sea floor and in the uppermost sediment column results in the colonization of hard-part surfaces by bacterial communities. Some of the metabolic redox processes related to these communities have the potential to alter carbonate shell properties, and hence affect earliest diagenetic pathways with significant consequences for archive data. During a three-month in vitro study, shell subsamples of the ocean quahog Arctica islandica (Linnaeus, 1767) were incubated in natural anoxic sediment slurries and bacterial culture medium of the heterotrophic Shewanella sediminisHAW-EB3. Bulk analyses of the liquid media from the Shewanella sediminis incubation revealed an over ten-fold increase in total alkalinity, dissolved inorganic carbon and ΩAragonite, and the alteration of the Mg/Ca, Mg/Sr and Sr/Ca ratios relative to control incubations without cultures. Ion ratios were most affected in the incubation with anoxic sediment, depicting a 25% decrease in Mg/Ca relative to the control. Shell sample surfaces that were exposed to both incubations displayed visible surface dissolution features, and an 8 wt% loss in calcium content. No such alteration features were detected in control shells. Apparently, alteration of shell carbonate properties was induced by microbially driven decomposition of shell intercrystalline organic constituents and subsequent opening of pathways for pore fluid-crystal exchange. This study illustrates the potential influence of benthic bacterial metabolism on biogenic carbonate archives during the initial stages of diagenetic alteration within a relatively short experimental duration of only three months. These results suggest that foremost the biological effect of bacterial cation adsorption on divalent cation ratios has the potential to complicate proxy interpretation. Results shown here highlight the necessity to consider bacterial metabolic activities in marine sediments for the interpretation of palaeo-environmental proxies from shell carbonate archives

Remdesivir for the treatment of COVID-19

Background Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the eMects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required. Objectives To assess the eMects of remdesivir compared to placebo or standard care alone-on clinical outcomes in hospitalised patients with SARSCoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach. Search methods We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021. Selection criteria We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases. Data collection and analysis We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen, non-invasive, or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for noninvasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, serious adverse events, and adverse events (any grade). Main results We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. Studies were mainly conducted in high- and upper-middle-income countries. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias assessments were considered to be some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals Remdesivir probably makes little or no diMerence to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk diMerence (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). There was limited evidence for a beneficial eMect of remdesivir on mortality in a subset of 435 participants who received low flow oxygen at baseline in one study (RR 0.32, 95% CI 0.15 to 0.66). We could not confirm this finding due to restricted availability of relevant subgroup data from other studies. Remdesivir may have little or no eMect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence). We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). Remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence). None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence). Authors' conclusions Based on the currently available evidence remdesivir probably has little or no eMect on all-cause mortality at up to 28 days in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the eMects of remdesivir on clinical improvement and worsening. There were insuMicient data available to examine the eMect of remdesivir on mortality across subgroups defined by respiratory support at baseline. Future studies should provide additional data on eMicacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for diMerent population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically