Non-Mass Transfer Limited Crystal Growth

There are many different active pharmaceutical ingredients (APIs) that have been discovered in research labs all around the world that can be used to treat and cure patients with a variety of different ailments. The challenge with these APIs in treatments is that they are not soluble in water, thus they low absorption into the blood stream (bio-availability). The key to making these APIs more bio-available is to understand how they grow as crystals and drop out of the aqueous solutions. One of the ways these APIs were made more bio-available is to render them amorphous and suspend them in an aqueous solution. After suspension in solution, the concentration of the API in the solution was measured every ten seconds while a seed crystal of the API was being rotated by a rotating disk apparatus (RDA). The data collected was then analyzed to see if at faster rotational speeds, the crystal growth rate would reach a maximum. This analysis will determine if there is a region where the drug’s growth is not limited by diffusion; it will help us with future experiments which include adding different cellulose based polymers to inhibit the integration of crystal growth molecules

Growth Of AlN Crystals On AlN/SiC Seeds By AlN Powder Sublimation In Nitrogen Atmosphere

AlN single crystals were grown on AlN/SiC seeds by sublimation of AlN powder in TaC crucibles in a nitrogen atmosphere. The seeds were produced by metallorganic chemical vapor deposition (MOCVD) of AlN on SiC crystals. The influence of growth temperature, growth time and source-toseed distance on the crystallinity and the crystal growth rate were investigated. Crystals were grown in an RF heated sublimation reactor at growth temperatures ranging from 1800-2000 °C, at a pressure of 600 Torr, nitrogen flow-rate of 100 sccm and source-to-seed distances of 10 and 35 mm. At 1870 °C and a source-to-seed distance of 35 mm, isolated crystals were observed with few instances of coalescence. At 1930 °C, a source-to-seed distance of 10 mm and longer growth times (~30 hrs), crystal coalescence was achieved. Above 1930 °C, the decomposition of SiC was evidently affecting the growth morphology and resulted in growth of polycrystalline AlN. After an initial nucleation period, the observed growth rates (10-30 μm/hr) were in close agreement with predictions of a growth model that assumed gas-phase diffusion controlled growth. Optical and electron microscope observations revealed step-flow growth, while X-ray diffraction results showed the single crystal nature of the grown material. Single crystalline AlN was grown over surface areas of 200-300 mm2 and was transparent and essentially colorless

Bringing Particle Scale Properties into Descriptions of Powder Behavior through the Enhanced Centrifuge Method

Inconsistent powder behavior introduces problems such as agglomeration, poor flowability, dust hazards, and segregation that decrease efficiency in powder processing environments. Understanding how a powder interacts with a surface at the particle scale provides insight into how to accommodate individual particle properties and avoid process deficiencies. This project uses an enhanced centrifuge technique to evaluate the adhesion between a stainless-steel surface and a powder comprised of fluorescent particles. Particles are deposited onto stainless steel plates which are rotated in a centrifuge. The adhesion properties are monitored by tracking the rotational speed at which particles of a known size are removed from the steel. To model the adhesion, a simulator was produced in MATLAB to map an ideal model to the experimental observations. In reality, the particles and steel are rough, and the particles are nonuniform in shape. The ideal case assumes the particles are smooth spheres and the steel is smooth. A modified van der Waals force model describes the observed forces. Within this model, a Hamaker constant, which usually describes only the effect of composition on the van der Waals force, is tuned to also describe the effects of the non-uniformity of the particles. This creates a distribution of ‘effective Hamaker constants’ that describes particle scale effects on the adhesion between the bulk powder and the stainless steel. This approach will allow industry to account for the effects of surface roughness, particle shape, and particle size when designing powder processing operations

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

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

Downstream oxygen etching characteristics of polymers from the parylene family

As dictated by the International Technology Roadmap for Semiconductors, there is an immediate need to develop low dielectric materials for use in metalization and packaging schemes in integrated circuits. The etching characteristics of a family of low dielectric polymers, the parylenes, are discussed. These are good models for polymer dielectrics, and are attractive for packaging applications. Three types of parylene are studied: parylene-N, parylene-C, and parylene AF-4. Parylene films on silicon substrates were etched in a downstream microwave oxygen plasma system. The goal was to characterize the chemical reactions that occurred on the parylene in the afterglow of the microwave oxygen plasma. The effect of temperature on the etch rate of each polymer was studied and an apparent activation energy was determined. The apparent activation energy for the etch process is approximately 7.0 kcal/mol for each polymer. Infrared analysis showed carbonyl formation during etching in the parylene-N and -C. Based on these analyses and the calculated activation energies, it was determined that a likely rate-limiting step in the etching was the ring opening

Downstream oxygen etching characteristics of polymers from the parylene family

As dictated by the International Technology Roadmap for Semiconductors, there is an immediate need to develop low dielectric materials for use in metalization and packaging schemes in integrated circuits. The etching characteristics of a family of low dielectric polymers, the parylenes, are discussed. These are good models for polymer dielectrics, and are attractive for packaging applications. Three types of parylene are studied: parylene-N, parylene-C, and parylene AF-4. Parylene films on silicon substrates were etched in a downstream microwave oxygen plasma system. The goal was to characterize the chemical reactions that occurred on the parylene in the afterglow of the microwave oxygen plasma. The effect of temperature on the etch rate of each polymer was studied and an apparent activation energy was determined. The apparent activation energy for the etch process is approximately 7.0 kcal/mol for each polymer. Infrared analysis showed carbonyl formation during etching in the parylene-N and -C. Based on these analyses and the calculated activation energies, it was determined that a likely rate-limiting step in the etching was the ring opening