Pre-Clinical Development of an Adenovirus Vector Based RSV and Shingles Vaccine Candidate.

Respiratory syncytial virus (RSV) infection and shingles are two viral diseases that affect older adults, and a combined vaccine to protect against both could be beneficial. RSV infection causes hospitalisations and significant morbidity in both children and adults and can be fatal in the elderly. The RSV fusion (F) envelope glycoprotein induces a strong RSV-neutralising antibody response and is the target of protective immunity in the first RSV vaccine for older adults, recently approved by the FDA.

Treatment escalation patterns to start biologics in refractory moderate juvenile dermatomyositis among members of the Childhood Arthritis and Rheumatology Research Alliance.

Background: Despite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM.

Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload.

Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized.

Removal of pregnancy categories and likelihood of prescribing: a randomized trial.

Objectives: To assess the degree to which removal of FDA' Pregnancy Categories (PC) of medications (A, B, C, and D) from labeling, affects the likelihood that providers will prescribe those medications.

Methods: Over a one-year period a convenience sample of providers was recruited into a randomized, survey-based, study. Two versions of the survey were randomly distributed; version 1 presented clinical vignettes, drug information, and PC, while version 2, presented the identical information without the PC.

Development and Evaluation of Bluetooth Low-Energy Device for Electronic Encounter Metrics.

The coronavirus disease 2019 (COVID-19) pandemic led to the need for tracking of physical contacts and potential exposure to disease. Traditional contact tracing can be augmented by electronic tools called "electronic contact tracing" or "exposure notification.".

Encounter Metrics and Exposure Notifcation.

We discuss the measurement of aggregate levels of encounters in a population, a concept we call encounter metrics. Encounter metrics are designed so that they can be deployed while preserving the privacy of individuals. To this end, encounters are labeled with a random number that cannot be linked to anything that is broadcast at the time of the encounter.

A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma.

Gold nanoparticles are promising drug delivery agents with the potential to deliver chemotherapeutic agents to tumour sites. The highly cytotoxic maytansinoid tubulin inhibitor DM1 has been attached to gold nanoparticles and shows tumour growth inhibition in mouse models of hepatocellular carcinoma. Attempting to improve the stability of the gold-cytotoxin bond led to the design and synthesis of novel maytansinoids with improved potency in cell viability assays and improved in vivo tolerability compared to the DM1 analogues.

The transition to consultant: Identifying gaps in higher specialist training.

Background: New consultants consistently feel better prepared for the clinical rather than non-clinical aspects of their role. However, deficiencies in generic competencies have been linked to burnout and patient complaints. This study explored how higher specialty training prepares doctors for the transition to consultant in genitourinary medicine.

Shifting attributions for poverty motivates opposition to inequality and enhances egalitarianism.

Amidst rising economic inequality and mounting evidence of its pernicious social effects, what motivates opposition to inequality? Five studies (n = 34,442) show that attributing poverty to situational forces is associated with greater concern about inequality, preference for egalitarian policies and inequality-reducing behaviour. In Study 1, situational attributions for poverty were associated with reduced support for inequality across 34 countries. Study 2 replicated these findings with a nationally representative sample of Americans.

Using Online Simulation of Pediatric Musculoskeletal Cases to Evaluate How Knowledge of Costs Affects Diagnostic Workup.

Background: Rising healthcare costs have emphasized the need to teach cost-conscious care in graduate medical education.

Objective: To teach high-value care and diagnostic evaluation of pediatric musculoskeletal complaints to residents and rotating medical students through online cases.

Methods: Six online cases were developed and tested at the University Hospitals Cleveland Medical Center.

Moment subset sums over finite fields.

The -subset sum problem over finite fields is a classical NP-complete problem. Motivated by coding theory applications, a more complex problem is the higher -th moment -subset sum problem over finite fields. We show that there is a deterministic polynomial time algorithm for the -th moment -subset sum problem over finite fields for each fixed when the evaluation set is the image set of a monomial or Dickson polynomial of any degree .

The Support for Economic Inequality Scale: Development and adjudication.

Past research has documented myriad pernicious psychological effects of high economic inequality, prompting interest into how people perceive, evaluate, and react to inequality. Here we propose, refine, and validate the Support for Economic Inequality Scale (SEIS)-a novel measure of attitudes towards economic inequality. In Study 1, we distill eighteen items down to five, providing evidence for unidimensionality and reliability.

Do time trade-off values fully capture attitudes that are relevant to health-related choices?

Previous research has shown that demographics, beliefs, and self-reported own health influence TTO values. Our hypothesis is that attitudes towards length and quality of life influence TTO values, but should no longer affect a set of related choices that are based on respondents' own TTO scores. A representative sample of 1339 respondents was asked their level of agreement to four statements relating to the importance of quality and length of life.

DM1 Loaded Ultrasmall Gold Nanoparticles Display Significant Efficacy and Improved Tolerability in Murine Models of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide with poor prognosis and limited options for treatment. Life expectancy after diagnosis is short; the currently available treatments are not well tolerated and have limited clinical benefit. There is a clear unmet clinical need for the development of new treatments.

Analysis of relationships between 25-hydroxyvitamin D, parathyroid hormone and cathelicidin with inflammation and cardiovascular risk in subjects with paediatric systemic lupus erythematosus: an Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study.

Objectives: Previous studies demonstrated associations between reduced serum 25-hydroxyvitamin D (25OHD), inflammation and disease activity in paediatric systemic lupus erythematosus (pSLE). The goal of this study was to assess parathyroid hormone (PTH) in its relationship to vitamin D and inflammation, as well as to better understand the role of human cathelicidin (LL-37) in pSLE.

Methods: Frozen serum samples collected at baseline of the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) study were assayed to determine 25OHD, PTH and LL-37 levels.

Comparing the importance of quality measurement themes in juvenile idiopathic inflammatory myositis between patients and families and healthcare professionals.

Background: A standardized set of quality measures for juvenile idiopathic inflammatory myopathies (JIIM) is not in use. Discordance has been shown between the importance ascribed to quality measures between patients and families and physicians. The objective of this study was to assess and compare the importance of various aspects of high quality care to patients with JIIM and their families with healthcare providers, to aid in future development of comprehensive quality measures.

Deprived, but not depraved: Prosocial behavior is an adaptive response to lower socioeconomic status.

Individuals of lower socioeconomic status (SES) display increased attentiveness to others and greater prosocial behavior compared to individuals of higher SES. We situate these effects within Pepper & Nettle's contextually appropriate response framework of SES. We argue that increased prosocial behavior is a contextually adaptive response for lower-SES individuals that serves to increase control over their more threatening social environments.

Social class and prosocial behavior: current evidence, caveats, and questions.

This review synthesizes research on social class and prosocial behavior. Individuals of lower social class display increased attention to others and greater sensitivity to others' welfare compared to individuals of higher social class, who exhibit more self-oriented patterns of social cognition. As a result, lower-class individuals are more likely to engage in other-beneficial prosocial behavior, whereas higher-class individuals are more prone to engage in self-beneficial behavior.

Perfused human hepatocyte microtissues identify reactive metabolite-forming and mitochondria-perturbing hepatotoxins.

Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

Objective: To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).

Methods: We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence.