Dimethylsulfide, climate and coral reef ecosystems

Dimethylsulfide (DMS) is the major biogenic source of atmospheric sulfur and is mainly derived from dimethylsulfoniopropionate (DMSP) produced by oceanic phytoplankton, marine algae and endosymbiont zooxanthellae in reef-building corals. Although coral reefs occupy <1% of the global oceans, the potential source strength of DMS from these areas was found to be significant in comparison to other oceanic areas. In this study, healthy nubbins of Acropora valida and Acropora pulchra collected at Heron Island were examined to assess the source strength of DMS from these common coral species. Total DMS (free DMS and DMSPderived DMS) measured in these corals was on average 3.6 μmol cm-2 surface area. Sediment from the coral reef flat was found to release ~1000 times less DMS than the Acropora corals when compared by weight. Megatonnes of DMS are released from the oceans to the atmosphere annually, where it is oxidised to contribute to new nanoparticles that can lead to cloud condensation nuclei (CCN). These affect cloud microphysical properties and consequently the Earth’s radiation budget and climate. The results suggest emissions of DMS from coral reefs are significant and may affect regional climate. Notably strong DMS plumes of up to 13 nmol m-3 of air were detected above the coral reef flat during low tide when it was exposed at the end of the day under calm conditions. A seasonal comparison of atmospheric DMS concentrations determined at Heron Island with a temperate marine location showed the reef to be a greater source of DMS

Can corals form aerosol particles through volatile sulphur compound emissions?

Acropora dominated coral reefs are a substantial source of atmospheric dimethylsulphide (DMSa), one of the most abundant reduced sulphur gases present in the marine boundary layer. DMS is believed to act as a climate regulator of solar radiation and sea surface temperatures through the formation of non-sea-salt sulphate aerosols and cloud condensation nuclei (CCN), although this regulation has not yet been demonstrated. A bubbling chamber experiment was conducted on coral reef seawater containing a branch of Acropora pulchra, to investigate whether the coral-generated DMSa could be oxidised to non-seasalt sulphate aerosols under treatment with UV light and O3. Results indicated that A. pulchra produced significant amounts of dimethylsulphoniopropionate (DMSP) and dissolved DMS although emissions of DMSa in the chamber headspace were reduced by the presence of the coral, probably as a result of antioxidant activity in the coral tissue. Significant amounts of carbon disulphide (CS2) and ethanethiol (ESH), other sulphur gases that could be involved in CCN formation, were also indicated in the bubbling chamber, most likely from coral production. A decrease in DMSa and CS2 in the presence of UV light and O3 followed by an occurrence of freshly nucleated nanoparticles (<10nm) suggested that these two sulphur compounds were oxidised and potentially participated in aerosol particle formation and thus could be involved in CCN formation and possibly climate regulation. The study provided insights into the production of sulphur compounds by Acropora dominated coral reefs with potential impact on local climate

Thirty years of evidence on the efficacy of drug treatments for chronic heart failure with reduced ejection fraction: A network meta-analysis

Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction

Cost-effectiveness analysis of sacubitril/valsartan vs enalapril in patients with heart failure and reduced ejection fraction

Importance  The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. Objective  To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. Design, Setting, and Participants  Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. Main Outcomes and Measures  Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. Results  The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of$45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to$75 301 per QALY. Conclusions and Relevance  For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril

Parameterizing the impact of seawater temperature and irradiance on dimethylsulfide (DMS) in the Great Barrier Reef and the contribution of coral reefs to the global sulfur cycle

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Jackson, R. L., Gabric, A. J., Matrai, P. A., Woodhouse, M. T., Cropp, R., Jones, G. B., Deschaseaux, E. S. M., Omori, Y., McParland, E. L., Swan, H. B., & Tanimoto, H. Parameterizing the impact of seawater temperature and irradiance on dimethylsulfide (DMS) in the Great Barrier Reef and the contribution of coral reefs to the global sulfur cycle. Journal of Geophysical Research:Oceans, 126(3), (2021): e2020JC016783, https://doi.org/10.1029/2020JC016783.Biogenic emissions of dimethylsulfide (DMS) are an important source of sulfur to the atmosphere, with implications for aerosol formation and cloud albedo over the ocean. Natural aerosol sources constitute the largest uncertainty in estimates of aerosol radiative forcing and climate and thus, an improved understanding of DMS sources is needed. Coral reefs are strong point sources of DMS; however, this coral source of biogenic sulfur is not explicitly included in climatologies or in model simulations. Consequently, the role of coral reefs in local and regional climate remains uncertain. We aim to improve the representation of tropical coral reefs in DMS databases by calculating a climatology of seawater DMS concentration (DMSw) and sea-air flux in the Great Barrier Reef (GBR), Australia. DMSw is calculated from remotely sensed observations of sea surface temperature and photosynthetically active radiation using a multiple linear regression model derived from field observations of DMSw in the GBR. We estimate that coral reefs and lagoon waters in the GBR (∼347,000 km2) release 0.03–0.05 Tg yr−1 of DMS (0.02 Tg yr−1 of sulfur). Based on this estimate, global tropical coral reefs (∼600,000 km2) could emit 0.08 Tg yr−1 of DMS (0.04 Tg yr−1 of sulfur), with the potential to influence the local radiative balance.Australian Research Council. Grant Number: DP150101649 National Science Foundation (NSF). Grant Number: 1543450 Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research. Grant Number: 23310016,16H02967,24241010,15H01732 Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Young Scientists. Grant Number: 17K1281

Superconducting routing platform for large-scale integration of quantum technologies

To reach large-scale quantum computing, three-dimensional integration of scalable qubit arrays and their control electronics in multi-chip assemblies is promising. Within these assemblies, the use of superconducting interconnections, as routing layers, offers interesting perspective in terms of (1) thermal management to protect the qubits from control electronics self-heating, (2) passive device performance with significant increase of quality factors and (3) density rise of low and high frequency signals thanks to minimal dispersion. We report on the fabrication, using 200 mm silicon wafer technologies, of a multi-layer routing platform designed for the hybridization of spin qubit and control electronics chips. A routing level couples the qubits and the control circuits through one layer of Al0.995Cu0.005 and superconducting layers of TiN, Nb or NbN, connected between them by W-based vias. Wafer-level parametric tests at 300 K validate the yield of these technologies and low temperature electrical measurements in cryostat are used to extract the superconducting properties of the routing layers. Preliminary low temperature radio-frequency characterizations of superconducting passive elements, embedded in these routing levels, are presented

Adv Ther

Purpose To compare visual outcomes and treatment burden between intravitreally administered aflibercept (IVT-AFL) and ranibizumab (RBZ) treat-and-extend (T&E) regimens in patients with wet age-related macular degeneration (wAMD) at 2 years. Methods A systematic literature review was carried out in Medline, EMBASE, and CENTRAL in October 2018. Matching-adjusted indirect comparison (MAIC) and/or individual patient data meta-regression was used to connect ALTAIR (assessing IVT-AFL T&E) with other studies, adjusting for between-trial differences in baseline visual acuity and age or baseline visual acuity, age, and polypoidal choroidal vasculopathy (PCV) status. Sensitivity analyses were conducted to test the robustness of the results, including direct MAIC between IVT-AFL T&E (ALTAIR) and RBZ T&E (CANTREAT and TREX-AMD trials). Results Six randomized controlled trials (RCTs) (ALTAIR, VIEW 1 and 2, CATT, CANTREAT, and TREX) were included in the analysis. IVT-AFL T&E was assessed in one study, ALTAIR (n = 255), while RBZ T&E was assessed in two trials (n = 327). At 2 years, the median difference (95% credibility interval) between IVT-AFL T&E and RBZ T&E regarding the numbers of Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained was not significant (M1: − 2.29 [− 8.10, 3.58]; M2: − 0.55 [− 6.34, 5.29]). IVT-AFL T&E was associated with significantly fewer injections than RBZ-T&E (M1: − 6.12 [− 7.60, − 4.65]; M2: − 5.93 [− 7.42, − 4.45]). Results of the sensitivity analyses were consistent with the main scenarios. Conclusion Patients with wAMD receiving an IVT-AFL T&E regimen achieved and maintained improvement in visual acuity with fewer injections over 2 years compared with RBZ T&E. IVT-AFL T&E may therefore serve as the optimal therapy for wAMD, as it was associated with clinical efficacy and minimized treatment burden

Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction.

OBJECTIVE: Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. METHODS: A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%-94% in the UK, 84% in Denmark and 95% in Colombia. CONCLUSIONS: Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF

Effects of a Ceramic Biomaterial on Immune Modulatory Properties and Differentiation Potential of Human Mesenchymal Stromal Cells of Different Origin.

The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammatory cytokines, MSCs similarly increased their suppressive capacities in the presence or absence of HA/TCP. The long-term culture of BM-MSCs with HA/TCP induced an osteoblast-like phenotype with upregulation of OSTERIX and OSTEOCALCIN, similar to what was obtained with dexamethasone and, to a higher extent, with bone morphogenetic protein 4 (BMP-4) treatment. MSC-derived osteoblasts did not trigger immune cell activation, but were less efficient than undifferentiated MSCs in inhibiting stimulated T and NK cells. Interestingly, their suppressive machinery included not only the activation of indoleamine-2,3 dioxygenase (IDO), which plays a central role in T-cell inhibition, but also cyclooxygenase-2 (COX-2) that was not significantly involved in the immune modulatory effect of human undifferentiated MSCs. Since COX-2 is significantly involved in bone healing, its induction by HA/TCP could also contribute to the therapeutic activity of MSCs for bone tissue engineering