Gas generation and wind power: A review of unlikely allies in the United Kingdom and Ireland

No single solution currently exists to achieve the utopian desire of zero fossil fuel electricity generation. Until such time, it is evident that the energy mix will contain a large variation in stochastic and intermittent sources of renewable energy such as wind power. The increasing prominence of wind power in pursuit of legally binding European energy targets enables policy makers and conventional generating companies to plan for the unique challenges such a natural resource presents. This drive for wind has been highly beneficial in terms of security of energy supply and reducing greenhouse gas emissions. However, it has created an unusual ally in natural gas. This paper outlines the suitability and challenges faced by gas generating units in their utilisation as key assets for renewable energy integration and the transition to a low carbon future. The Single Electricity Market of the Republic of Ireland and Northern Ireland and the British Electricity Transmission Trading Agreement Market are the backdrop to this analysis. Both of these energy markets have a reliance on gas generation matching the proliferation of wind power. The unlikely and mostly ignored relationship between natural gas generation and wind power due to policy decisions and market forces is the necessity of gas to act as a bridging fuel. This review finds gas generation to be crucially important to the continued growth of renewable energy. Additionally, it is suggested that power market design should adequately reward the flexibility required to securely operate a power system with high penetrations of renewable energy, which in most cases is provided by gas generation

The effects of stochastic resonance electrical stimulation and neoprene sleeve on knee proprioception

<p>Abstract</p> <p>Background</p> <p>A variety of knee injuries and pathologies may cause a deficit in knee proprioception which may increase the risk of reinjury or the progression of disease. Stochastic resonance stimulation is a new therapy which has potential benefits for improving proprioceptive function. The objective of this study was to determine if stochastic resonance (SR) stimulation applied with a neoprene sleeve could improve knee proprioception relative to a no-stimulation/no-sleeve condition (control) or a sleeve alone condition in the normal, healthy knee. We hypothesized that SR stimulation when applied with a sleeve would enhance proprioception relative to the control and sleeve alone conditions.</p> <p>Methods</p> <p>Using a cross-over within subject design, twenty-four healthy subjects were tested under four combinations of conditions: electrical stimulation/sleeve, no stimulation/sleeve, no stimulation/no sleeve, and stimulation/no sleeve. Joint position sense (proprioception) was measured as the absolute mean difference between a target knee joint angle and the knee angle reproduced by the subject. Testing was conducted during both partial-weight bearing (PWB) and non-weight bearing (NWB) tasks. Differences in joint position sense between the conditions were evaluated by repeated-measures analysis of variance testing.</p> <p>Results</p> <p>Joint position sense error during the stimulation/sleeve condition (2.48° ± 1.32°) was found to be more accurate (P < 0.05) relative to the control condition (3.35° ± 1.63°) in the PWB task. No difference in joint position sense error was found between stimulation/sleeve and sleeve alone conditions for the PWB task. Joint position sense error was not found to differ between any of the conditions for the NWB task.</p> <p>Conclusion</p> <p>These results suggest that SR electrical stimulation when combined with a neoprene sleeve is an effective modality for enhancement of joint proprioception in the PWB knee. We believe these results suggest the need for further study of the potential of SR stimulation to correct proprioceptive deficits in a clinical population with knee injury/pathology or in subjects at risk of injury because of a proprioceptive deficit.</p

Effectiveness of Mechanisms and Models of Coordination between Organizations, Agencies and Bodies Providing or Financing Health Services in Humanitarian Crises: A Systematic Review.

BACKGROUND: Effective coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises is required to ensure efficiency of services, avoid duplication, and improve equity. The objective of this review was to assess how, during and after humanitarian crises, different mechanisms and models of coordination between organizations, agencies and bodies providing or financing health services compare in terms of access to health services and health outcomes. METHODS: We registered a protocol for this review in PROSPERO International prospective register of systematic reviews under number PROSPERO2014:CRD42014009267. Eligible studies included randomized and nonrandomized designs, process evaluations and qualitative methods. We electronically searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and the WHO Global Health Library and websites of relevant organizations. We followed standard systematic review methodology for the selection, data abstraction, and risk of bias assessment. We assessed the quality of evidence using the GRADE approach. RESULTS: Of 14,309 identified citations from databases and organizations' websites, we identified four eligible studies. Two studies used mixed-methods, one used quantitative methods, and one used qualitative methods. The available evidence suggests that information coordination between bodies providing health services in humanitarian crises settings may be effective in improving health systems inputs. There is additional evidence suggesting that management/directive coordination such as the cluster model may improve health system inputs in addition to access to health services. None of the included studies assessed coordination through common representation and framework coordination. The evidence was judged to be of very low quality. CONCLUSION: This systematic review provides evidence of possible effectiveness of information coordination and management/directive coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises. Our findings can inform the research agenda and highlight the need for improving conduct and reporting of research in this field

The Community IntraVenous Antibiotic Study (CIVAS): a mixed methods evaluation of patient preferences for and cost effectiveness of different service models for delivering outpatient parenteral antimicrobial therapy

Background: Outpatient parenteral antimicrobial therapy (OPAT) is widely used in most developed countries, providing considerable opportunities for improved cost savings. However, it is implemented only partially in the UK, using a variety of service models. Objectives: The aims of this research were to (1) establish the extent of OPAT service models in England and identify their development; (2) evaluate patients’ preferences for different OPAT service delivery models; (3) assess the cost-effectiveness of different OPAT service delivery models; and (4) convene a consensus panel to consider our evidence and make recommendations. Methods: This mixed-methods study included seven centres providing OPAT using four main service models: (1) hospital outpatient (HO) attendance; (2) specialist nurse (SN) visiting at home; (3) general nurse (GN) visiting at home; and (4) self-administration (SA) or carer administration. Health-care providers were surveyed and interviewed to explore the implementation of OPAT services in England. OPAT patients were interviewed to determine key service attributes to develop a discrete choice experiment (DCE). This was used to perform a quantitative analysis of their preferences and attitudes. Anonymised OPAT case data were used to model cost-effectiveness with both Markov and simulation modelling methods. An expert panel reviewed the evidence and made recommendations for future service provision and further research. Results: The systematic review revealed limited robust literature but suggested that HO is least effective and SN is most effective. Qualitative study participants felt that different models of care were suited to different types of patient and they also identified key service attributes. The DCE indicated that type of service was the most important factor, with SN being strongly preferred to HO and SA. Preferences were influenced by attitudes to health care. The results from both Markov and simulation models suggest that a SN model is the optimal service for short treatment courses (up to 7 days). Net monetary benefit (NMB) values for HO, GN and SN services were £2493, £2547 and £2655, respectively. For longer treatment, SA appears to be optimal, although SNs provide slightly higher benefits at increased cost. NMB values for HO, GN, SN and SA services were £8240, £9550, £10,388 and £10,644, respectively. The simulation model provided useful information for planning OPAT services. The expert panel requested more guidance for service providers and commissioners. Overall, they agreed that mixed service models were preferable. Limitations: Recruitment to the qualitative study was suboptimal in the very elderly and ethnic minorities, so the preferences of patients from these groups might not be represented. The study recruited from Yorkshire, so the findings may not be applicable nationally. Conclusions: The quantitative preference analysis and economic modelling favoured a SN model, although there are differences between sociodemographic groups. SA provides cost savings for long-term treatment but is not appropriate for all. Future work: Further research is necessary to replicate our results in other regions and populations and to evaluate mixed service models. The simulation modelling and DCE methods used here may be applicable in other health-care settings. Funding: The National Institute for Health Research Health Service and Delivery Research programme

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline