10+ years of the IEA-GHG Weyburn-Midale CO2 monitoring and storage project: Successes and lessons learned from multiple hydrogeological investigations

AbstractIn July 2000, the IEA-GHG Weyburn CO2 monitoring and storage project was initiated to study the geological storage of CO2 as part of an EOR project planned for the Weyburn Field in Saskatchewan, Canada. Over the period 2000-present, a diverse group of researchers have worked on: assessing the integrity of the geosphere encompassing the Weyburn oil pool for effective long-term storage of CO2; monitoring the movement of the injected CO2, and assessing the risk of migration of CO2 from the injection zone to the surface. Learnings from 10+ years of hydrogeological investigations include: (i) low flow rates and favourable flow directions indicate the Weyburn reservoir is an excellent place to store CO2; (ii) shallow groundwater monitoring reveals no significant changes in water chemistry that can be attributed to storage operations (interactions); and (iii) co-ordination and integration of multiple hydrogeological research programs on the same site can be rewarding but challenging

Characterization of the Aquistore CO2 project storage site, Saskatchewan, Canada

AbstractAquistore is a new integrated Carbon Capture and Storage demonstration project in southeastern Saskatchewan, Canada. An extensive geological, geophysical, petrophysical, hydrogeological, and geochemical characterization program was undertaken using both pre-existing and newly-acquired data at this site. Data were assembled into several geological models that were used to support planning and permitting of the project. Carbon dioxide will be injected into a permeable sandstone interval approximately 150m thick using a newly-drilled 3400m deep injection well and monitored, in part, using a new 3400m deep instrumented observation well that is 150m away from the injection well. All of the integrated characterization work at the site thus far indicates strongly favorable conditions for geological CO2 storage in the subsurface at Aquistore

The impact of renal artery stenting on therapeutic aims

Renal artery stenosis manifests as poorly-controlled hypertension, impaired renal function or pulmonary oedema, therefore the success of treatment is dependent on indication. This study aims to determine the outcomes of patients undergoing renal artery stenting (RASt) based on therapeutic aim compared to criteria used in the largest randomised trial. Retrospective case-note review of patients undergoing RASt between 2008–2021 (n = 74). The cohort was stratified by indication for intervention (renal dysfunction, hypertension, pulmonary oedema) and criteria employed in the CORAL trial, with outcomes and adverse consequences reported. Intervention for hypertension achieved significant reduction in systolic blood pressure and antihypertensive agents at 1 year (median 43 mmHg, 1 drug), without detrimental impact on renal function. Intervention for renal dysfunction reduced serum creatinine by a median 124 μmol/L, sustained after 6 months. Intervention for pulmonary oedema was universally successful with significant reduction in SBP and serum creatinine sustained at 1 year. Patients who would have been excluded from the CORAL trial achieved greater reduction in serum creatinine than patients meeting the inclusion criteria, with equivalent blood pressure reduction. There were 2 procedure-related mortalities and 5 procedural complications requiring further intervention. 5 patients had reduction in renal function following intervention and 7 failed to achieve the intended therapeutic benefit. Renal artery stenting is effective in treating the indication for which it has been performed. Previous trials may have underestimated the clinical benefits by analysis of a heterogenous population undergoing a procedure rather than considering the indication, and excluding patients who would maximally benefit

A study of the impact of individual thermal control on user comfort in the workplace: Norwegian cellular vs. British open plan offices

In modern offices, user control is being replaced by centrally operated thermal systems, and in Scandinavia, personal offices by open plan layouts. This study examined the impact of user control on thermal comfort and satisfaction. It compared a workplace, which was designed entirely based on individual control over the thermal environment, to an environment that limited thermal control was provided as a secondary option for fine-tuning: Norwegian cellular and British open plan offices. The Norwegian approach provided each user with control over a window, door, blinds, heating and cooling as the main thermal control system. In contrast, the British practice provided a uniform thermal environment with limited openable windows and blinds to refine the thermal environment for occupants seated around the perimeter of the building. Field studies of thermal comfort were applied to measure users’ perception of thermal environment, empirical building performance and thermal control. The results showed a 30% higher satisfaction and 18% higher comfort level in the Norwegian offices compared to the British practices. However, the energy consumption of the Norwegian case studies was much higher compared to the British ones. A balance is required between energy efficiency and user thermal comfort in the workplace

Coaching as a social process

In this conceptual paper, we argue the importance to the coaching profession of a critical understanding of coaching as a social process, in order to promote coaching as an enabler for change, and facilitate its use in other cultures and challenging contexts. We start with a critical analysis of the origin of coaching, arguing that neoliberal values have been embedded in the discourse of coaching. We also discuss the impact of coaching as an instrumental and ideological device, sometimes used in organisations as a process of control, and suggest that understanding coaching as a social process has the potential to transform it into an enabler for change. We propose a framework for understanding how different philosophical positions affect the way coaches may respond to the challenges of intercultural or oppressive social contexts. We conclude with a discussion of the implications for coaching research and development

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

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570