Covering systems with the sum of the reciprocals of the moduli close to 11

In 1952, H. Davenport posed the problem of determining a condition on the minimum modulus $m_{0}$ in a finite distinct covering system that would imply that the sum of the reciprocals of the moduli in the covering system is bounded away from $1$. In 1973, P. Erdos and J. Selfridge indicated that they believed that $m_{0} > 4$ would suffice. We provide a proof that this is the case

C‐reactive protein flare‐response predicts long‐term efficacy to first‐line anti‐PD‐1‐based combination therapy in metastatic renal cell carcinoma

Objectives Immune checkpoint blockade (IO) has revolutionised the treatment of metastatic renal cell carcinoma (mRCC). Early C-reactive protein (CRP) kinetics, especially the recently introduced CRP flare-response phenomenon, has shown promising results to predict IO efficacy in mRCC, but has only been studied in second line or later. Here, we aimed to validate the predictive value of early CRP kinetics for 1st-line treatment of mRCC with αPD-1 plus either αCTLA-4 (IO+IO) or tyrosine kinase inhibitor (IO+TKI). Methods In this multicentre retrospective study, we investigated the predictive potential of early CRP kinetics during 1st-line IO therapy. Ninety-five patients with mRCC from six tertiary referral centres with either IO+IO (N = 59) or IO+TKI (N = 36) were included. Patients were classified as CRP flare-responders, CRP responders or non-CRP responders as previously described, and their oncological outcome was compared. Results Our data validate the predictive potential of early CRP kinetics in 1st-line immunotherapy in mRCC. CRP responders, especially CRP flare-responders, had significantly prolonged progression-free survival (PFS) compared with non-CRP responders (median PFS: CRP flare-responder: 19.2 months vs. responders: 16.2 vs. non-CRP responders: 5.6, P < 0.001). In both the IO+IO and IO+TKI subgroups, early CRP kinetics remained significantly associated with improved PFS. CRP flare-response was also associated with long-term response ≥ 12 months. Conclusions Early CRP kinetics appears to be a low-cost and easy-to-implement on-treatment biomarker to predict response to 1st-line IO combination therapy. It has potential to optimise therapy monitoring and might represent a new standard of care biomarker for immunotherapy in mRCC

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

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

Environmental assessment of an integrated adaptive system for the improvement of indoor visual comfort of existing buildings

This research aims to propose and evaluate an integrated adaptive system consisting of individual movable modules for the improvement of indoor environmental conditions. The system was evaluated by means of a natural lighting analysis simulation using Ecotect v5.2 and Desktop Radiance v1.02. Daylighting performance indicators, i.e. daylight factor (DF) and uniformity daylight factor (UDF), were calculated for various geometrical configurations. The analysis suggests that the integration of the system in appropriate geometrical configurations maintains high percentages of the plan area exceeding 2% DF, while it drastically increases UDF above the threshold of 0.40. Moreover, an in-depth analysis of natural lighting levels was performed for south-facing spaces during different periods of the year and hours of the day. In the majority of the cases under study, the proposed system maintains a high percentage of the plan area with lighting levels above 500 lux, while it significantly decreases the percentage of area exceeding 3000 lux and thus minimizes the possibilities of glare issues. The research study confirms the positive contribution of the proposed system as a natural lighting regulation system, while it establishes the concept of prosthetic renovation as a renewable energy strategy for the improvement of indoor comfort of existing buildings

Environmental assessment of an integrated adaptive system for the improvement of indoor visual comfort of existing buildings

This research aims to propose and evaluate an integrated adaptive system consisting of individual movable modules for the improvement of indoor environmental conditions. The system was evaluated by means of a natural lighting analysis simulation using Ecotect v5.2 and Desktop Radiance v1.02. Daylighting performance indicators, i.e. daylight factor (DF) and uniformity daylight factor (UDF), were calculated for various geometrical configurations. The analysis suggests that the integration of the system in appropriate geometrical configurations maintains high percentages of the plan area exceeding 2% DF, while it drastically increases UDF above the threshold of 0.40. Moreover, an in-depth analysis of natural lighting levels was performed for south-facing spaces during different periods of the year and hours of the day. In the majority of the cases under study, the proposed system maintains a high percentage of the plan area with lighting levels above 500 lux, while it significantly decreases the percentage of area exceeding 3000 lux and thus minimizes the possibilities of glare issues. The research study confirms the positive contribution of the proposed system as a natural lighting regulation system, while it establishes the concept of prosthetic renovation as a renewable energy strategy for the improvement of indoor comfort of existing buildings

Environmental assessment of an integrated adaptive system for the improvement of indoor visual comfort of existing buildings

This research aims to propose and evaluate an integrated adaptive system consisting of individual movable modules for the improvement of indoor environmental conditions. The system was evaluated by means of a natural lighting analysis simulation using Ecotect v5.2 and Desktop Radiance v1.02. Daylighting performance indicators, i.e. daylight factor (DF) and uniformity daylight factor (UDF), were calculated for various geometrical configurations. The analysis suggests that the integration of the system in appropriate geometrical configurations maintains high percentages of the plan area exceeding 2% DF, while it drastically increases UDF above the threshold of 0.40. Moreover, an in-depth analysis of natural lighting levels was performed for south-facing spaces during different periods of the year and hours of the day. In the majority of the cases under study, the proposed system maintains a high percentage of the plan area with lighting levels above 500 lux, while it significantly decreases the percentage of area exceeding 3000 lux and thus minimizes the possibilities of glare issues. The research study confirms the positive contribution of the proposed system as a natural lighting regulation system, while it establishes the concept of prosthetic renovation as a renewable energy strategy for the improvement of indoor comfort of existing buildings

A Roadmap for the Integration of Active Solar Systems into Buildings

This paper aims to simplify the interdisciplinary design process that will be used as a design tool for the viable integration of active solar energy systems into buildings, i.e., Building-Integrated Solar Thermal Systems—BISTSs; Building-Integrated Photovoltaic Systems—BIPVSs, through the creation of a roadmap. The research also aims supplement the work of researchers who have dealt with the creation of design tools that aim to optimise a specific aspect of a building design, or their geometric forms, in order to shape energy-efficient and sustainable architectural solutions. More specifically, a prescriptive design strategy is derived from the proposed design tool. This is based on five design steps, each of which is analysed and which lead to the creation of a comprehensive design tool for siting buildings so as to optimise the integration of solar systems. The originality of this tool is based on the fact that it makes an important step in the standardisation of these studies.</jats:p

Integration of a lightweight plug-in adaptive envelope to maximize performance of natural lighting of existing buildings

The main objective of this paper is to investigate the environmental renovation of multi-storey buildings through the integration of a lightweight plug-in adaptive envelope. The adaptive envelope incorporates a series of passive environmental strategies to achieve indoor conditions improvement, with emphasis on natural lighting performance. The creation of an advanced envelope design also affects the architectural appearance of the building itself and of the city in general. Given that the proposed envelope is intended for mass production and application on existing buildings, parameters such as the structural system, as well as the construction techniques and materials applied, are taken into consideration. Additionally, the research takes into account the constructability of the unit components and their ability to be deformed, adapting their shape according to the environmental requirements of the system. The geometrical configuration and adaptive behaviour of the plug-in envelope is modelled using parametric associative design tools. For evaluation purposes, visual analysis software simulation has been employed. The simulation results are presented and discussed on a comparative basis, indicating the potentials of the proposed façade system to be used effectively for the improvement of natural lighting performance and glare issues of indoor spaces in existing buildings and consequently of their lighting performance