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

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

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

Calculating total health service utilisation and costs from routinely collected electronic health records using the example of patients with irritable bowel syndrome before and after their first gastroenterology appointment

INTRODUCTION: Health economic models are increasingly important in funding decisions but most are based on data, which may therefore not represent the general population. We sought to establish the potential of real-world data available within the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) to determine comprehensive healthcare utilisation and costs as input variables for economic modelling. METHODS: A cohort of patients with irritable bowel syndrome (IBS) who first saw a gastroenterologist in 2008 or 2009, and with 3 years of data before and after their appointment, was created in the CPRD. Primary care, outpatient, inpatient, prescription and colonoscopy data were extracted from the linked CPRD and HES. The appropriate cost to the NHS was attached to each event. Total and stratified annual healthcare utilisation rates and costs were calculated before and after the gastroenterology appointment with distribution parameters. Absolute differences were calculated with 95 % confidence intervals. RESULTS: Total annual healthcare costs over 3 years increase by £935 (95 % CI £928–941) following a gastroenterology appointment for IBS. We derived utilisation and cost data with parameter distributions stratified by demographics and time. Women, older patients, smokers and patients with greater comorbidity utilised more healthcare resources, which generated higher costs. CONCLUSIONS: These linked datasets provide comprehensive primary and secondary care data for large numbers of patients, which allows stratification of outcomes. It is possible to derive input parameters appropriate for economic models and their distributions directly from the population of interest

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

Perivascular cells for regenerative medicine

Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We and others recently described that MSC originate from two types of perivascular cells, namely pericytes and adventitial cells and contain the in situ counterpart of MSC in developing and adult human organs, which can be prospectively purified using well defined cell surface markers. Pericytes encircle endothelial cells of capillaries and microvessels and express the adhesion molecule CD146 and the PDGFRβ, but lack endothelial and haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is a pericyte marker exclusively associated with the arterial system. Besides its expression in smooth muscle cells, smooth muscle actin (αSMA) is also detected in subsets of pericytes. Adventitial cells surround the largest vessels and, opposite to pericytes, are not closely associated to endothelial cells. Adventitial cells express CD34 and lack αSMA and all endothelial and haematopoietic cell markers, as for pericytes. Altogether, pericytes and adventitial perivascular cells express in situ and in culture markers of MSC and display capacities to differentiate towards osteogenic, adipogenic and chondrogenic cell lineages. Importantly, adventitial cells can differentiate into pericyte-like cells under inductive conditions in vitro. Altogether, using purified perivascular cells instead of MSC may bring higher benefits to regenerative medicine, including the possibility, for the first time, to use these cells uncultured

Osteodifferentiated Mesenchymal Stem Cells from Bone Marrow and Adipose Tissue Express HLA-G and Display Immunomodulatory Properties in HLA-Mismatched Settings: Implications in Bone Repair Therapy

Mesenchymal stem cells (MSCs) are multipotent cells that can be obtained from several sources such as bone marrow and adipose tissue. Depending on the culture conditions, they can differentiate into osteoblasts, chondroblasts, adipocytes, or neurons. In this regard, they constitute promising candidates for cell-based therapy aimed at repairing damaged tissues. In addition, MSCs display immunomodulatory properties through the expression of soluble factors including HLA-G. We here analyse both immunogenicity and immunosuppressive capacity of MSCs derived from bone marrow and adipose tissue before and after osteodifferentiation. Results show that HLA-G expression is maintained after osteodifferentiation and can be boosted in inflammatory conditions mimicked by the addition of IFN-γ and TNF-α. Both MSCs and osteodifferentiated MSCs are hypoimmunogenic and exert immunomodulatory properties in HLA-mismatched settings as they suppress T cell alloproliferation in mixed lymphocyte reactions. Finally, addition of biomaterials that stimulate bone tissue formation did not modify MSC immune properties. As MSCs combine both abilities of osteoregeneration and immunomodulation, they may be considered as allogenic sources for the treatment of bone defects

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