Investigation of the particle growth of fenofibrate following antisolvent precipitation and freeze-drying

peer-reviewedSubmicron to small-micron-sized particles of the hydrophobic drug, fenofibrate, were prepared by controlled crystallization in order to influence its dissolution behavior. An antisolvent precipitation process successfully generated particles (200-300 nm) which matched the size and dissolution behavior of a commercial wet-milled formulation of the drug. Although the preparation of submicron-sized particles was straightforward, retaining their size in suspension and during isolation was a challenge. Additives were employed to temporarily stabilize the suspension, and extend the time window for isolation of the submicron particles. Precipitated particles were isolated primarily by immediate freeze-drying, but drying stresses were found to destabilize the fragile submicron system. The growth pathway of particles in suspension and during oven and freeze-drying were compared. Although the growth pathways appeared considerably different from a visual morphological perspective, an investigation of the electron diffraction patterns and the inner-particle surfaces showed that the growth pathways were the same: molecular addition by Ostwald ripening. The observed differences in the time-resolved particle morphologies were found to be a result of the freeze-drying process.ACCEPTEDpeer-reviewe

Prevalence of Asymptomatic SARS-CoV-2 Infection in Children and Adults in Marion County, Indiana

Background and Objectives: Two community studies outside the US showed asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adults, but not in children <10 years of age. In this study, we assessed the prevalence of asymptomatic SARS-CoV-2 infection in children and adults in Marion County, Indiana. Methods: Individuals living in Marion County with no symptoms of coronavirus 2019 disease (COVID-19) within seven days of enrollment were eligible for this cross-sectional household study. Study kits were delivered to the participant’s residence for self-swabbing, picked up by the study team, and tested by polymerase chain reaction (PCR) for SAR-CoV-2 infection. Results: Five hundred eleven nasal swabs were collected from 119 children and 392 adults ≥18 years of age. One participant (seven years of age) tested positive, for an overall study prevalence of 0.2% (95% CI 0, 0.6%). The participant had no known contact with a person with SARS-CoV-2 infection, and five family members tested negative for infection. The child and family members all tested negative for infection 10 and 20 days after the first test, and none developed symptoms of COVID-19 for 20 days after testing. Conclusions: Asymptomatic SARS-CoV-2 infection can occur in children <10 years with no known COVID-19 exposure. Large cohort studies should be conducted to determine prevalence of asymptomatic infection and risk of transmission from asymptomatic infection in children and adults over time

Evaluating Providers’ Prescription Opioid Instructions to Pediatric Patients

Receiving an opioid prescription during childhood increases the risk of hazardous prescription opioid (PO) use during emerging adulthood. Instruction on how to safely use POs plays an essential role in pediatric patients’ capacity to utilize as well as to discontinue POs appropriately. This study aimed to evaluate pediatric PO label instructions provided to a large sample of pediatric outpatients. Data were extracted from the electronic healthcare records system identifying pediatric patients who received a PO between 2016 and 2019 from pediatric outpatient medical clinics were affiliated with a northwestern United States medical center and children’s hospital. Pediatric patients (n = 12,613) between 0–17 years old who received a PO during outpatient care were included. Patients with chronic health conditions (e.g., cancer) or who received their PO from an inpatient medical setting were excluded. Patient demographics, medication instructions, associated diagnoses, and other prescription information (e.g., name of medication, dose, and quantity dispensed) were examined using automated text classification. Many label instructions did not include any indication/reason for use (20.8%). Virtually none of the POs (\u3e99%) included instructions for how to reduce/wean off POs, contact information for questions about the POs, and/or instructions around how to dispose of the POs. Efforts are needed to ensure that pediatric PO instructions contain essential elements to improve comprehension of when and how to use POs for pediatric patients

Perspectives on Astrophysics Based on Atomic, Molecular, and Optical (AMO) Techniques

About two generations ago, a large part of AMO science was dominated by experimental high energy collision studies and perturbative theoretical methods. Since then, AMO science has undergone a transition and is now dominated by quantum, ultracold, and ultrafast studies. But in the process, the field has passed over the complexity that lies between these two extremes. Most of the Universe resides in this intermediate region. We put forward that the next frontier for AMO science is to explore the AMO complexity that describes most of the Cosmos.Comment: White paper submission to the Decadal Assessment and Outlook Report on Atomic, Molecular, and Optical (AMO) Science (AMO 2020

Baker Center Journal of Applied Public Policy, Vol. I No. I

Welcome to the first issue of the Baker Center Journal of Applied Public Policy. Throughout my many years of service, I always have been impressed with the tremendous good that can be accomplished through the creation and implementation of sound public policy. I hope that, along the way, I have contributed to the body of policies that help our nation function in a strong, effective, compassionate, and prosperous fashion. As we launch this new Journal, under the auspices of the Howard H. Baker Jr. Center for Public Policy at the University of Tennnnessee, I wanted to briefly expand on some of the reasons I believe that this journal is necessary and why I believe that research on public policy is so vitally important. This Journal aims to discuss applied public policy. The goal is not to engage in theoretical discussions, though I believe those are important. Instead, we hope that the Baker Journal will focus on the most current issues that directly affect our nation and our world on the operational, or mechanical level. We intend to engage a wide variety of contributors. Scholars, of course, will be asked to write on critical topics of research. We also aim to include contributions from those who draft, approve and execute public policy at the local, state, and national levels. Additionally, at least one article in each issue will be reserved for the work of a university-level student. Our approach is varied, and I know that the result will be an intellectually sound and extraordinarily interesting presentation of experiences and ideas.I am especially pleased that so many University of Tennnnessee students are involved in the formulation and operation of the Journal. Our editorial board is comprised of some of the University of Tennnnessee’s most promising undergraduate, graduate, and law school students. With dedicated assistance and oversight from faculty and from the Baker Center, this board of extraordinarily intelligent and committed students has worked very hard to make this Journal a reality. The Center has also formed a national advisory panel for the Journal. I am a member of that panel, and I must note that I am grateful for the involvement and support of my colleagues who have agreed to serve with me: Ms. Emily Reynolds, former Secretary of the United States Senate; Congressman Bob Clement, former Tennnnessee Congressman; Mr. Glennnn Reynolds, noted author and professor of law at the University of Tennnnessee; Dr. Joseph Cooper, an accomplished professor of political science at Johns Hopkins University; and Mr. John Seigenthaler, distinguished journalist and founder and director of the First Amendment Center at Vanderbilt University. I believe it is critical that we think deeply about the issues that are confronting us today. Our representative system of governance is based on an informed citizenry and informed public servants. From international issues such as the war on terror and energy challenges to more local but equally important topics such as sustainable development and education, we must commit ourselves to understanding all challenges free of partisan rhetoric. Only then can we confront them together. It is my hope that this Journal will add to that understanding and will speak to many audiences. From the classroom to the boardroom, from city hall to the halls of our legislatures, I believe the work put forward in our journal will be useful for everyone who wants to be informed and engaged. It is an exciting undertaking, and I thank you for your support

The Efficacy of Sunitinib Treatment of Renal Cancer Cells Is Associated with the Protein PHAX In Vitro

Anti-angiogenic agents, such as the multi-tyrosine kinase inhibitor sunitinib, are key first line therapies for metastatic clear cell renal cell carcinoma (ccRCC), but their mechanism of action is not fully understood. Here, we take steps towards validating a computational prediction based on differential transcriptome network analysis that phosphorylated adapter RNA export protein (PHAX) is associated with sunitinib drug treatment. The regulatory impact factor differential network algorithm run on patient tissue samples suggests PHAX is likely an important regulator through changes in genome-wide network connectivity. Immunofluorescence staining of patient tumours showed strong localisation of PHAX to the microvasculature consistent with the anti-angiogenic effect of sunitinib. In normal kidney tissue, PHAX protein abundance was low but increased with tumour grade (G1 vs. G3/4; p 0.01), consistent with a possible role in cancer progression. In organ culture, ccRCC cells had higher levels of PHAX protein expression than normal kidney cells, and sunitinib increased PHAX protein expression in a dose dependent manner (untreated vs. 100 µM; p 0.05). PHAX knockdown in a ccRCC organ culture model impacted the ability of sunitinib to cause cancer cell death (p 0.0001 untreated vs. treated), suggesting a role for PHAX in mediating the efficacy of sunitinib

Comparative analysis of c-kit gene expression and c-Kit immunoreactivity in horses with and without obstructive intestinal disease

Previous immunohistochemical studies targeting the receptor tyrosine kinase (c-Kit) have demonstrated an apparent reduction in the number of gastrointestinal pacemaker cells--the interstitial cells of Cajal (ICC)--in horses with intestinal motility disorders. This study compared the level of transcription of the c-kit gene encoding this receptor in horses with and without such motility disorders. Transcription levels of this gene were also compared to the density of ICC immunohistochemically positive for the c-Kit antigen. Intestinal samples were collected from 18 horses with intestinal disease and from 15 control animals. Following gene extraction and identification, real-time quantitative analysis of c-kit and a control gene, ACTB (β-actin), was carried out on all samples and the density of the c-Kit-positive ICC compared. There was a significant reduction in c-Kit immunoreactivity in the ICC of horses with large intestinal obstructive disorders relative to controls but no significant difference in the transcription of the c-kit gene between normal and affected animals. Further studies will be required to elucidate the mechanisms regulating c-Kit expression and to assess the pathophysiological significance of these findings

Scaling Up Mental Health Services in Zambia: Challenges and Opportunities Reported in an Education Project.

yesThe need to increase the capacity of developing countries to meet the mental health needs of their populations is widely acknowledged. This article examines some of the challenges associated with a British Council DelPHE project aimed at strengthening the capacity of mental health educators to prepare the mental health workforce in Zambia for a shift from an institutional to a community-based model of care. The analysis draws on data from two focus groups in which the participants were drawn from college educators who had taken part in workshops intended to enhance curriculum alignment to ensure that the education and training provided for clinical officers (psychiatry) and mental health nurses was "fit for purpose." In particular, the article highlights their perspectives on some of the tensions in focusing on mental health as opposed to broader health care and in ensuring appropriate opportunities for practice or field placements. The continuing impact of stigma and limited resources available for mental ill-health is acknowledged within the wider context of inequities in mental health care. Findings of this evaluation may be applicable to other sub-Saharan contexts, but should be understood only within the Zambian context

A Systematic Review of Mosquito Coils and Passive Emanators: Defining Recommendations for Spatial Repellency Testing Methodologies.

Mosquito coils, vaporizer mats and emanators confer protection against mosquito bites through the spatial action of emanated vapor or airborne pyrethroid particles. These products dominate the pest control market; therefore, it is vital to characterize mosquito responses elicited by the chemical actives and their potential for disease prevention. The aim of this review was to determine effects of mosquito coils and emanators on mosquito responses that reduce human-vector contact and to propose scientific consensus on terminologies and methodologies used for evaluation of product formats that could contain spatial chemical actives, including indoor residual spraying (IRS), long lasting insecticide treated nets (LLINs) and insecticide treated materials (ITMs). PubMed, (National Centre for Biotechnology Information (NCBI), U.S. National Library of Medicine, NIH), MEDLINE, LILAC, Cochrane library, IBECS and Armed Forces Pest Management Board Literature Retrieval System search engines were used to identify studies of pyrethroid based coils and emanators with key-words "Mosquito coils" "Mosquito emanators" and "Spatial repellents". It was concluded that there is need to improve statistical reporting of studies, and reach consensus in the methodologies and terminologies used through standardized testing guidelines. Despite differing evaluation methodologies, data showed that coils and emanators induce mortality, deterrence, repellency as well as reduce the ability of mosquitoes to feed on humans. Available data on efficacy outdoors, dose-response relationships and effective distance of coils and emanators is inadequate for developing a target product profile (TPP), which will be required for such chemicals before optimized implementation can occur for maximum benefits in disease control