On-site peer mentorship's effect on personal and professional development, stress reduction, and ease of transition into the medical education system.

Context: Mentorship aids in the transition into the medical education system, which is a demanding and stressful time for learners. The development of new medical schools to offset the physician shortage has posed a challenge in that the inaugural class of students lacks an upperclassman cohort as a resource for advice and mentorship. Mentorship has proven to have positive impacts on three domains: personal and professional development (PPD), stress reduction (SR), and ease of transition (ET) into medical school.

Determination of the effect of iatrogenic blood contamination on lactate dehydrogenase and creatine kinase activity in canine cerebrospinal fluid.

Background: Lactate dehydrogenase (LDH) and creatine kinase (CK) have differential tissue activity and isoenzyme profiles. LDH and CK exist as 5 and 3 isoenzymes, respectively, in both serum and cerebrospinal fluid (CSF). Studies have demonstrated that measuring LDH, CK, and their isoenzymes in CSF has diagnostic and prognostic values for dogs and people with neurologic disorders.

The Effectiveness of Riparian Hedgerows at Intercepting Drift from Aerial Pesticide Application.

The primary tool used currently for preventing pesticide drift from entering streams is a no-spray buffer zone. Riparian hedgerows may provide an additional option; however, quantitative information on their effectiveness is limited. To quantify the potential benefit of riparian hedgerows for drift reduction, aerial malathion {diethyl 2-[(dimethoxyphosphorothioyl)sulfanyl]butanedioate} applications on blueberry ( L.

Pharmacokinetics and physiologic/behavioral effects of buprenorphine administered sublingually and intravenously to neonatal foals.

Buprenorphine is absorbed following sublingual administration, which would be a low-stress delivery route in foals. However, the pharmacokinetics/pharmacodynamics are not described in foals. Six healthy foals <21 days of age participated in a blinded, randomized, 3-period, 5-sequence, 3-treatment crossover prospective study.

Rational Selection, Criticality Assessment, and Tiering of Quality Attributes and Test Methods for Analytical Similarity Evaluation of Biosimilars.

Leading regulatory agencies recommend biosimilar assessment to proceed in a stepwise fashion, starting with a detailed analytical comparison of the structural and functional properties of the proposed biosimilar and reference product. The degree of analytical similarity determines the degree of residual uncertainty that must be addressed through downstream in vivo studies. Substantive evidence of similarity from comprehensive analytical testing may justify a targeted clinical development plan, and thus enable a shorter path to licensing.

Monitoring Shelf Life of Pasteurized Whole Milk Under Refrigerated Storage Conditions: Predictive Models for Quality Loss.

Unlabelled: The shelf life of pasteurized milk is generally determined through microbiological analysis. The objective of this study was to correlate microbial quality parameters then to design predictive models for shelf life of pasteurized milk. We analyzed pasteurized milk (3.

A pilot study of an autologous tumor-derived autophagosome vaccine with docetaxel in patients with stage IV non-small cell lung cancer.

Background: Tumor-derived autophagosome vaccines (DRibbles) have the potential to broaden immune response to poorly immunogenic tumors.

Methods: Autologous vaccine generated from tumor cells harvested from pleural effusions was administered to patients with advanced NSCLC with the objectives of assessing safety and immune response. Four patients were vaccinated and evaluable for immune response; each received two to four doses of vaccine.

Effect of simulator orientation during skills training on performance of basic laparoscopic tasks by veterinary students.

OBJECTIVE To determine whether basic laparoscopic skills acquired during training in the horizontal plane would transfer to the vertical plane and vice versa. DESIGN Evaluation study. SAMPLE POPULATION 26 first- and second-year veterinary students with no prior laparoscopic skills training or surgical experience.

Statistical Approaches to Assess Biosimilarity from Analytical Data.

Protein therapeutics have unique critical quality attributes (CQAs) that define their purity, potency, and safety. The analytical methods used to assess CQAs must be able to distinguish clinically meaningful differences in comparator products, and the most important CQAs should be evaluated with the most statistical rigor. High-risk CQA measurements assess the most important attributes that directly impact the clinical mechanism of action or have known implications for safety, while the moderate- to low-risk characteristics may have a lower direct impact and thereby may have a broader range to establish similarity.

Bioassay case study applying the maximin D-optimal design algorithm to the four-parameter logistic model.

Cell-based potency assays play an important role in the characterization of biopharmaceuticals but they can be challenging to develop in part because of greater inherent variability than other analytical methods. Our objective is to select concentrations on a dose-response curve that will enhance assay robustness. We apply the maximin D-optimal design concept to the four-parameter logistic (4 PL) model and then derive and compute the maximin D-optimal design for a challenging bioassay using curves representative of assay variation.

Systematic verification of bioanalytical similarity between a biosimilar and a reference biotherapeutic: committee recommendations for the development and validation of a single ligand-binding assay to support pharmacokinetic assessments.

For biosimilar drug development, it is critical to demonstrate similar physiochemical characteristics, efficacy, and safety of the biosimilar product compared to the reference product. Therefore, pharmacokinetic (PK) and immunogenicity (antidrug antibody, ADA) assays that allow for the demonstration of biosimilarity are critical. Under the auspices of the American Association of Pharmaceutical Scientists (AAPS) Ligand-Binding Assay Bioanalytical Focus Group (LBABFG), a Biosimilars Action Program Committee (APC) was formed in 2011.

OX40 is a potent immune-stimulating target in late-stage cancer patients.

OX40 is a potent costimulatory receptor that can potentiate T-cell receptor signaling on the surface of T lymphocytes, leading to their activation by a specifically recognized antigen. In particular, OX40 engagement by ligands present on dendritic cells dramatically increases the proliferation, effector function, and survival of T cells. Preclinical studies have shown that OX40 agonists increase antitumor immunity and improve tumor-free survival.

Phase 1 study of stereotactic body radiotherapy and interleukin-2--tumor and immunological responses.

Preclinical models suggest that focal high-dose radiation can make tumors more immunogenic. We performed a pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) to assess safety and tumor response rate and perform exploratory immune monitoring studies. Patients with metastatic melanoma or renal cell carcinoma (RCC) who had received no previous medical therapy for metastatic disease were eligible.

Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms.

Previously, we reported that combination treatment with rat amylin (100 microg/kg.d) and murine leptin (500 microg/kg.d) elicited greater inhibition of food intake and greater body weight loss in diet-induced obese rats than predicted by the sum of the monotherapy conditions, a finding consistent with amylin-induced restoration of leptin responsiveness.

A Bayesian approach to utilizing prior data in new drug development.

In this paper we propose a Bayesian method to combine safety data collected from two separate drug development programs using the same active drug substance but for different indications, formulations, or patient populations. The objective of combining the data across the programs is to better define the level of safety risk associated with the new indication or target population. There may be adverse events (AEs) observed in the new program that represent new safety signals.

Combination therapy with amylin and peptide YY[3-36] in obese rodents: anorexigenic synergy and weight loss additivity.

Circulating levels of the pancreatic beta-cell peptide hormone amylin and the gut peptide PYY[3-36] increase after nutrient ingestion. Both have been implicated as short-term signals of meal termination with anorexigenic and weight-reducing effects. However, their combined effects are unknown.

Effects of prior or concurrent food restriction on amylin-induced changes in body weight and body composition in high-fat-fed female rats.

Amylin infusion reduces food intake and slows body weight gain in rodents. In obese male rats, amylin (but not pair feeding) caused a preferential reduction of fat mass with protein preservation despite equal body weight loss in amylin-treated (fed ad libitum) and pair-fed rats. In the present study, the effect of prior or concurrent food restriction on the ability of amylin to cause weight loss was evaluated.

The simultaneous analysis of discrete and continuous outcomes in a dose-response study: using desirability functions.

Multiple types of outcomes are sometimes measured on each animal in toxicology dose-response experiments. The potential false-positive rate from statistical tests on each endpoint may be inflated. We introduce a method of deriving a composite score that combines information from discrete and continuous outcomes through the use of desirability functions.

Thermoregulatory response to an organophosphate and carbamate insecticide mixture: testing the assumption of dose-additivity.

Most toxicity data are based on studies using single compounds. This study assessed if there is an interaction between mixtures of the anticholinesterase insecticides chlorpyrifos (CHP) and carbaryl (CAR) using hypothermia and cholinesterase (ChE) inhibition as toxicological endpoints. Core temperature (T(c)) was continuously monitored by radiotelemetry in adult Long-Evans rats administered CHP at doses ranging from 0 to 50mg/kg and CAR doses of 0-150 mg/kg.

D-optimal experimental designs to test for departure from additivity in a fixed-ratio mixture ray.

Traditional factorial designs for evaluating interactions among chemicals in a mixture may be prohibitive when the number of chemicals is large. Using a mixture of chemicals with a fixed ratio (mixture ray) results in an economical design that allows estimation of additivity or nonadditive interaction for a mixture of interest. This methodology is extended easily to a mixture with a large number of chemicals.

The crisis in orthodontic education: goals and perceptions.

A crisis in orthodontic education exists today because of a shortage of qualified people seeking to pursue careers in academic orthodontics; 35% of orthodontic graduate programs in the United States report having at least 1 vacant faculty position. Previous studies have identified several factors that contribute to the current shortage. The purpose of this study was to quantify and compare real and perceived differences in income, workload, and other qualitative characteristics between academic and private practice orthodontists.

Burkholderia cepacia complex in cystic fibrosis: frequency of strain replacement during chronic infection.

Persons with cystic fibrosis (CF) are susceptible to chronic pulmonary infection due to certain Burkholderia species, but it is not clear whether this typically involves persistent infection with the same strain or sequential infection with distinct strains. We analyzed 1095 Burkholderia isolates recovered from serial sputum cultures from 379 patients with CF receiving care in 112 CF treatment centers in the United States. Genotyping was performed by random amplified polymorphic DNA typing or pulsed-field gel electrophoresis.

Valuing health-related quality of life in diabetes.

Objective: Cost-utility analyses use information on health utilities to compare medical treatments that have different clinical outcomes and impacts on survival. The purpose of this study was to describe the health utilities associated with diabetes and its treatments, complications, and comorbidities.

Research Design And Methods: We studied 2,048 subjects with type 1 and type 2 diabetes recruited from specialty clinics at a university medical center.