Successes, Challenges and Opportunities for Environmental Barrier Coatings

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Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

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

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Les effets de la prise de médicaments par les patients sur le déplacement dentaire en orthodontie

Le remodelage des tissus péridentaires est un élément capital du déplacement dentaire en orthodontie, et des réponses optimales aux traitements ne sont obtenues que par une application avisée des forces. L’utilisation, chez certains patients, de médicaments pour traiter diverses pathologies peut modifier ce remodelage et augmenter ou diminuer la vitesse de déplacement des dents. La plupart des revues de littérature se sont concentrées sur les anti-inflammatoires non stéroïdiens (AINS) et leurs effets sur la réduction de la vitesse de ce déplacement. Cet article passe en revue les données relatives aux effets des pathologies systémiques sur le mécanisme du déplacement dentaire, et met l’accent sur les médicaments spécifiques utilisés par les patients. Il est destiné à donner une base de données de référence à l’usage des orthodontistes et des médecins d’autres spécialités, afin de mieux gérer les effets principaux et secondaires des médicaments sur le déplacement dentaire. Est également soulignée l’importance pour les orthodontistes d’obtenir une liste complète de tous les médicaments pris par chaque patient, aussi bien avant que pendant le traitement

Metabolomics Analysis of Human Vitreous in Diabetic Retinopathy and Rhegmatogenous Retinal Detachment

The vitreous humor is a highly aqueous eye fluid interfacing with the retina and lens and providing shape. Its molecular composition provides a readout for the eye’s physiological status. Changes in cellular metabolism underlie vitreoretinal pathologies, but despite routine surgical collection of vitreous, only limited reports of metabolism in the vitreous of human patients have been described. Vitreous samples from patients with rhegmatogenous retinal detachment (<i>n</i> = 25) and proliferative diabetic retinopathy (<i>n</i> = 9) were profiled along with control human vitreous samples (<i>n</i> = 8) by untargeted mass-spectrometry-based metabolomics. Profound changes were observed in diabetic retinopathy vitreous, including altered glucose metabolism and activation of the pentose phosphate pathway, which provides reducing equivalents to counter oxidative stress. In addition, purine metabolism was altered in diabetic retinopathy, with decreased xanthine and elevated levels of related purines (inosine, hypoxanthine, urate, allantoate) generated in oxidant-producing reactions. In contrast, the vitreous metabolite profiles of retinal detachment patients were similar to controls. In total, our results suggest a rewiring of vitreous metabolism in diabetic retinopathy that underlies disease features such as oxidative stress and furthermore illustrates how the vitreous metabolic profile may be impacted by disease

Metabolomics Analysis of Human Vitreous in Diabetic Retinopathy and Rhegmatogenous Retinal Detachment

The vitreous humor is a highly aqueous eye fluid interfacing with the retina and lens and providing shape. Its molecular composition provides a readout for the eye’s physiological status. Changes in cellular metabolism underlie vitreoretinal pathologies, but despite routine surgical collection of vitreous, only limited reports of metabolism in the vitreous of human patients have been described. Vitreous samples from patients with rhegmatogenous retinal detachment (<i>n</i> = 25) and proliferative diabetic retinopathy (<i>n</i> = 9) were profiled along with control human vitreous samples (<i>n</i> = 8) by untargeted mass-spectrometry-based metabolomics. Profound changes were observed in diabetic retinopathy vitreous, including altered glucose metabolism and activation of the pentose phosphate pathway, which provides reducing equivalents to counter oxidative stress. In addition, purine metabolism was altered in diabetic retinopathy, with decreased xanthine and elevated levels of related purines (inosine, hypoxanthine, urate, allantoate) generated in oxidant-producing reactions. In contrast, the vitreous metabolite profiles of retinal detachment patients were similar to controls. In total, our results suggest a rewiring of vitreous metabolism in diabetic retinopathy that underlies disease features such as oxidative stress and furthermore illustrates how the vitreous metabolic profile may be impacted by disease

The Next Generation Arecibo Telescope: A preliminary study

The Next Generation Arecibo Telescope (NGAT) was a concept presented in a white paper Roshi et al. (2021) developed by members of the Arecibo staff and user community immediately after the collapse of the 305 m legacy telescope. A phased array of small parabolic antennas placed on a tiltable plate-like structure forms the basis of the NGAT concept. The phased array would function both as a transmitter and as a receiver. This envisioned state of the art instrument would offer capabilities for three research fields, viz. radio astronomy, planetary and space & atmospheric sciences. The proposed structure could be a single plate or a set of closely spaced segments, and in either case it would have an equivalent collecting area of a parabolic dish of size 300 m. In this study we investigate the feasibility of realizing the structure. Our analysis shows that, although a single structure ~300 m in size is achievable, a scientifically competitive instrument 130 to 175 m in size can be developed in a more cost effective manner. We then present an antenna configuration consisting of one hundred and two 13 m diameter dishes. The diameter of an equivalent collecting area single dish would be ~130 m, and the size of the structure would be ~146 m. The weight of the structure is estimated to be 4300 tons which would be 53% of the weight of the Green Bank Telescope. We refer to this configuration as NGAT-130. We present the performance of the NGAT-130 and show that it surpasses all other radar and single dish facilities. Finally, we briefly discuss its competitiveness for radio astronomy, planetary and space & atmospheric science applications.Comment: 6 pages, 5 figures, 1 table, Invited paper for the ICEAA-IEEE APWC conference, Venice, Italy, Oct 9-13, 202

A Greener IIT (Semester Unknown) IPRO 326: AGreenerIITIPRO326FinalReportSp10

IIT’s core vision is built around the principle that no matter how good we get, we can always improve. As the University seeks to assert itself as a member of the top tier of academic institutions in the U.S., there are many ideas for improvement up for implementation. Among these ideas is the goal to make IIT the most sustainable, urban university campus in the United States. IPRO 326 (“A Greener IIT”) is based upon the idea that in order to accomplish this, we must improve the sustainability of IIT’s main campus landscape.Deliverable

A Greener IIT (Semester Unknown) IPRO 326: AGreenerIITIPRO326PosterSp10

IIT’s core vision is built around the principle that no matter how good we get, we can always improve. As the University seeks to assert itself as a member of the top tier of academic institutions in the U.S., there are many ideas for improvement up for implementation. Among these ideas is the goal to make IIT the most sustainable, urban university campus in the United States. IPRO 326 (“A Greener IIT”) is based upon the idea that in order to accomplish this, we must improve the sustainability of IIT’s main campus landscape.Deliverable