The Judicial Expansion of American Exceptionalism

The percolation theory is established as a useful tool in the field of pharmaceutical materials science.It is shown that percolation theory, developed for analyzing insulator–conductor transitions, can beapplied to describe imperfect dc conduction in pharmaceutical microcrystalline cellulose duringdensification. The system, in fact, exactly reproduces the values of the percolation threshold andexponent estimated for a three-dimensional random continuum. Our data clearly show a crossoverfrom a power-law percolation theory region to a linear effective medium theory region at a celluloseporosity of ;0.7

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

Densification-induced conductivity percolation in high-porosity pharmaceutical microcrystalline cellulose compacts

The percolation theory is established as a useful tool in the field of pharmaceutical materials science.It is shown that percolation theory, developed for analyzing insulator–conductor transitions, can beapplied to describe imperfect dc conduction in pharmaceutical microcrystalline cellulose duringdensification. The system, in fact, exactly reproduces the values of the percolation threshold andexponent estimated for a three-dimensional random continuum. Our data clearly show a crossoverfrom a power-law percolation theory region to a linear effective medium theory region at a celluloseporosity of ;0.7

Moisture sorption by cellulose powders of varying crystallinity

Abstract Moisture in microcrystalline cellulose may cause stability problems for moisture sensitive drugs. The aim of this study was to investigate the influence of crystallinity and surface area on the uptake of moisture in cellulose powders. Powders of varying crystallinity were manufactured, and the uptake of moisture was investigated at different relative humidities. The structure of the cellulose powders was characterized by X-ray diffraction, BET surface area analysis, and scanning electron microscopy. Moisture uptake was directly related to the cellulose crystallinity and pore volume: Cellulose powders with higher crystallinity showed lower moisture uptake at relative humidities below 75%, while at higher humidities the moisture uptake could be associated with filling of the large pore volume of the cellulose powder of highest crystallinity. In conclusion, the structure of cellulose should be thoroughly considered when manufacturing low moisture grades of MCC

Combined vitamin D, ibuprofen and glutamic acid decarboxylase-alum treatment in recent onset Type i diabetes : Lessons from the DIABGAD randomized pilot trial

Aim: Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D). Methods: 64 patients (T1D since <4 months, age 10-17.99, fasting sC-peptide ≥0.12 nmol/l, GADA-positive) were randomized into Day(D) 1-90 400 mg/day Ibuprofen, D1-450 vitamin D 2000 IU/day, D15, 45 sc. 20 μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40 μg GAD-alum D15, 45; placebo. Results: Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24 h with change in C-peptide AUC at 15 months (r = -0.776, p < 0.0001). Conclusion: Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov). Lay abstract In many countries, Type I diabetes with insufficient own insulin secretion is a common life-threatening disease in children and adults. There is no prevention and no cure. In spite of very intense treatment, the disease leads to serious complications. There is no efficaceous method to save own insulin secretion without serious risks and adverse events, but autoantigen treatment with glutamic acid decarboxylase has shown some efficacy. We have tried a combination therapy with vitamin D and anti-inflammatory treatment (ibuprofen). Vitamin D in combination with glutamic acid decarboxylase-alum seems to have beneficial effects, but not Ibuprofen. The effect is influenced by basal clinical and immunological status