Chapter Potentials and Challenges of Additive Manufacturing Technologies for Heat Exchanger

The rapid development of additive manufacturing (AM) technologies enables a radical paradigm shift in the construction of heat exchangers. In place of a layout limited to the use of planar or tubular starting materials, heat exchangers can now be optimized, reflecting their function and application in a particular environment. The complexity of form is no longer a restriction but a quality. Instead of brazing elements, resulting in rather inflexible standard components prone to leakages, with AM, we finally can create seamless integrated and custom solutions from monolithic material. To address AM for heat exchangers we both focus on the processes, materials, and connections as well as on the construction abilities within certain modeling and simulation tools. AM is not the total loss of restrictions. Depending on the processes used, delicate constraints have to be considered. But on the other hand, we can access materials, which can operate in a much wider heat range. It is evident that conventional modeling techniques cannot match the requirements of a flexible and adaptive form finding. Instead, we exploit biomimetic and mathematical approaches with parametric modeling. This results in unseen configurations and pushes the limits of how we should think about heat exchangers today

Potentials and Challenges of Additive Manufacturing Technologies for Heat Exchanger

The rapid development of additive manufacturing (AM) technologies enables a radical paradigm shift in the construction of heat exchangers. In place of a layout limited to the use of planar or tubular starting materials, heat exchangers can now be optimized, reflecting their function and application in a particular environment. The complexity of form is no longer a restriction but a quality. Instead of brazing elements, resulting in rather inflexible standard components prone to leakages, with AM, we finally can create seamless integrated and custom solutions from monolithic material. To address AM for heat exchangers we both focus on the processes, materials, and connections as well as on the construction abilities within certain modeling and simulation tools. AM is not the total loss of restrictions. Depending on the processes used, delicate constraints have to be considered. But on the other hand, we can access materials, which can operate in a much wider heat range. It is evident that conventional modeling techniques cannot match the requirements of a flexible and adaptive form finding. Instead, we exploit biomimetic and mathematical approaches with parametric modeling. This results in unseen configurations and pushes the limits of how we should think about heat exchangers today

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

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

Chapter Potentials and Challenges of Additive Manufacturing Technologies for Heat Exchanger

The rapid development of additive manufacturing (AM) technologies enables a radical paradigm shift in the construction of heat exchangers. In place of a layout limited to the use of planar or tubular starting materials, heat exchangers can now be optimized, reflecting their function and application in a particular environment. The complexity of form is no longer a restriction but a quality. Instead of brazing elements, resulting in rather inflexible standard components prone to leakages, with AM, we finally can create seamless integrated and custom solutions from monolithic material. To address AM for heat exchangers we both focus on the processes, materials, and connections as well as on the construction abilities within certain modeling and simulation tools. AM is not the total loss of restrictions. Depending on the processes used, delicate constraints have to be considered. But on the other hand, we can access materials, which can operate in a much wider heat range. It is evident that conventional modeling techniques cannot match the requirements of a flexible and adaptive form finding. Instead, we exploit biomimetic and mathematical approaches with parametric modeling. This results in unseen configurations and pushes the limits of how we should think about heat exchangers today