Initial Construct Validity Evidence of a Virtual Human Application for Competency Assessment in Breaking Bad News to a Cancer Patient

Background: Despite interest in using virtual humans (VHs) for assessing health care communication, evidence of validity is limited. We evaluated the validity of a VH application, MPathic-VR, for assessing performance-based competence in breaking bad news (BBN) to a VH patient. Methods: We used a two-group quasi-experimental design, with residents participating in a 3-hour seminar on BBN. Group A (n=15) completed the VH simulation before and after the seminar, and Group B (n=12) completed the VH simulation only after the BBN seminar to avoid the possibility that testing alone affected performance. Pre-and postseminar differences for Group A were analyzed with a paired t-test, and comparisons between Groups A and B were analyzed with an independent t-test. Results: Compared to the preseminar result, Group A\u27s postseminar scores improved significantly, indicating that the VH program was sensitive to differences in assessing performance-based competence in BBN. Postseminar scores of Group A and Group B were not significantly different, indicating that both groups performed similarly on the VH program. Conclusion: Improved pre-post scores demonstrate acquisition of skills in BBN to a VH patient. Pretest sensitization did not appear to influence posttest assessment. These results provide initial construct validity evidence that the VH program is effective for assessing BBN performance-based communication competence

Understanding and optimising the transfection of lipopolyplexes formulated in saline: the effects of peptide and serum

Lipopolyplexes (LPDs) are of considerable interest for use as gene delivery vehicles. Here LPDs have been prepared from cationic vesicles (composed of a 1 : 1 molar ratio of DOTMA with the neutral helper lipid, DOPE), singly branched cationic peptides and plasmid DNA. All peptides contained a linker sequence (cleaved by endosomal furin) attached to a targeting sequence selected to bind human airway epithelial cells and mediate gene delivery. The current study investigates the effects of novel Arg-containing cationic peptide sequences on the biophysical and transfection properties of LPDs. Mixed His/Arg cationic peptides were of particular interest, as these sequences have not been previously used in LPD formulations. Lengthening the number of cationic residues in a homopolymer from 6 to 12 in each branch reduced transfection using LPDs, most likely due to increased DNA compaction hindering the release of pDNA within the target cell. Furthermore, LPDs containing mixed Arg-containing peptides, particularly an alternating Arg/His sequence exhibited an increase in transfection, probably because of their optimal ability to complex and subsequently release pDNA. To confer stability in serum, LPDs were prepared in 0.12 M sodium chloride solution (as opposed to the more commonly used water) yielding multilamellar LPDs with very high levels of size reproducibility and DNA protection, especially when compared to the (unilamellar) LPDs formed in water. Significantly for the clinical applications of the LPDs, those prepared in the presence of sodium chloride retained high levels of transfection in the presence of media supplemented with fetal bovine serum. This work therefore represents a significant advance for the optimisation of LPD formulation for gene delivery, under physiologically relevant conditions, in vivo

The Ursinus Weekly, November 10, 1966

Delta Pi\u27s queen reigns at annual Homecoming • U.C. students aid delinquents • Founder\u27s Day emphasizes church relationship: Three honorary degrees conferred • U.C. poetry reading • CBS reporter to speak at Forum • Behind the scenes innovations • Faculty team at War College • Local businesses educate employees • Editorial: Salvation; The moon is down • On cinnamon and seething • Letters to the editor: If you can\u27t win fairly, cheat? • Book review • New faculty building announced; Program gains momentum • Freeland\u27s ghost laments disrespect for traditions • Lyndon Johnson in Collegeville? Recent visit proves possibility: Receives giant welcome from Polish • Dickinson tops Bears in fourth quarter, 13-10 • Booters blank Delaware; Lose to Swarthmore, Haverford • Alfred whips UC, 60-8 • Cross country team wins seven of first eight • Swarthmore ruins Homecoming, 21-6 • Hockey team undefeated; Trips W.C. 1-0 • Ursinus fares well at All College • Intramural report • Ursinus hockey team beats Wilson 3-0 • First and third teams combine to down Temple 5-0 • Greek gleanings • Chapel schedulehttps://digitalcommons.ursinus.edu/weekly/1193/thumbnail.jp

Learning and Reflection in the Midst of Persistent Challenges on Practicing School Leaders’ Time

Among the many scarce resources that principals must conserve and use wisely, time may present one of the more persistent challenges to their leadership practices. A simultaneous and equally challenging practice for school leaders is engaging in systematic reflection that serves to mitigate time constraints and emotional upheavals of the job. Reflection, and resistance to it, emerged as a theme during a yearlong-program that emerged from a school-university partnership, focused on the development of district-level coaches to support experienced principals in becoming more reflective leaders for continuous school improvement. The program uncovered principals’ resistance to the pauses in their practices that reflection requires. These principals and coaches also reported emotional reactions to persisting mandates on school accountability. This paper offers some insights into how reflection may balance the ongoing emotional dynamics and time constraints of schooling, and the degree to which the mentoring program supported principal protégés in this effort

White matter microstructure in 22q11 deletion syndrome: a pilot diffusion tensor imaging and voxel-based morphometry study of children and adolescents

Young people with 22q11 Deletion Syndrome (22q11DS) are at substantial risk for developing psychosis and have significant differences in white matter (WM) volume. However, there are few in vivo studies of both WM microstructural integrity (as measured using Diffusion Tensor (DT)-MRI) and WM volume in the same individual. We used DT-MRI and structural MRI (sMRI) with voxel based morphometry (VBM) to compare, respectively, the fractional anisotropy (FA) and WM volume of 11 children and adolescents with 22q11DS and 12 controls. Also, within 22q11DS we related differences in WM to severity of schizotypy, and polymorphism of the catechol-O-methyltransferase (COMT) gene. People with 22q11DS had significantly lower FA in inter-hemispheric and brainstem and frontal, parietal and temporal lobe regions after covarying for IQ. Significant WM volumetric increases were found in the internal capsule, anterior brainstem and frontal and occipital lobes. There was a significant negative correlation between increased schizotypy scores and reduced WM FA in the right posterior limb of internal capsule and the right body and left splenium of corpus callosum. Finally, the Val allele of COMT was associated with a significant reduction in both FA and volume of WM in the frontal lobes, cingulum and corpus callosum. Young people with 22q11DS have significant differences in both WM microstructure and volume. Also, there is preliminary evidence that within 22q11DS, some regional differences in FA are associated with allelic variation in COMT and may perhaps also be associated with schizotypy

Novel cationic lipopolyplexes as gene therapy vectors

A major obstacle in the development of gene therapy is delivery of therapeutic genes to the desired cell/tissue. The objective of our study is to use a non-viral ternary system (lipopolyplexes) to encapsulate and deliver therapeutic DNA. Our lipopolyplexes comprise a glycerol-based cytofectin, a targeting peptide and plasmid DNA. Novel derivatives of the cationic lipids DOTMA and DOTAP have been synthesized and tested in a breast cancer cell line. A range of branched cationic peptides varying in number of residues, composition and linker to a targeting head group were also designed and prepared. The bio-physical studies demonstrated that all LPD complexes were positively charged, small (60-80 nm) and were shown to effectively condense DNA. Gel assays showed which peptides were able to protect DNA more effectively and gave high transfection efficiency. Further studies are underway investigating these systems in siRNA delivery

Tuning a gene delivery vector: the role of peptide sequence and peptide branching in delivering of DNA and siRNA to the cytoplasm

Tuning a gene delivery vector: the role of peptide sequence and peptide branching in delivering of DNA and siRNA to the cytoplas

Pharmacokinetics and safety of intravenously administered citrulline in children undergoing congenital heart surgery: Potential therapy for postoperative pulmonary hypertension

ObjectivePulmonary hypertension may complicate surgical correction of congenital heart defects, resulting in increased morbidity and mortality. We have previously shown that plasma levels of the nitric oxide precursors citrulline and arginine drop precipitously after congenital cardiac surgery and that oral citrulline supplementation may be protective against the development of pulmonary hypertension. In this study, we assessed the safety and pharmacokinetic profile of intravenous citrulline as a potential therapy for postoperative pulmonary hypertension.MethodsThe initial phase of this investigation was a dose-escalation study of intravenously administered citrulline in infants and children undergoing one of five congenital cardiac surgical procedures (phase 1). The primary safety outcome was a 20% drop in mean arterial blood pressure from the baseline pressure recorded after admission to the intensive care unit. Based on our previous work, the target circulating plasma citrulline trough was 80 to 100 μmol/L. Each patient was given two separate doses of citrulline: the first in the operating room immediately after initiation of cardiopulmonary bypass and the second 4 hours later in the pediatric intensive care unit. Stepwise dose escalations included 50 mg/kg, 100 mg/kg, and 150 mg/kg. After model-dependent pharmacokinetic analysis, we enrolled an additional 9 patients (phase 2) in an optimized dosing protocol that replaced the postoperative dose with a continuous infusion of citrulline at 9 mg/(kg·h) for 48 hours postoperatively.ResultsThe initial stepwise escalation protocol (phase 1) revealed that an intravenous citrulline dose of 150 mg/kg given after initiation of cardiopulmonary bypass yielded a trough level of in the target range of approximately 80 to 100 μmol/L 4 hours later. The postoperative dose revealed that the clearance of intravenously administered citrulline was 0.6 L/(h·kg), with a volume of distribution of 0.9 L/kg and estimated half-life of 60 minutes. Because of the short half-life, we altered the protocol to replace the postoperative dose with a continuous infusion of 9 mg/(kg·h). An additional 9 patients were studied with this continuous infusion protocol (phase 2). Mean plasma citrulline levels were maintained at approximately 125 μmol/L, with a calculated clearance of 0.52 L/(h·kg). None of the 17 patients studied had a 20% drop in mean arterial blood pressure from baseline.ConclusionsIn this first report of the use of intravenous citrulline in humans, we found citrulline to be both safe and well tolerated in infants and young children undergoing congenital cardiac surgery. Because of the rapid clearance, the optimal dosing regimen was identified as an initial bolus of 150 mg/kg given at the initiation of cardiopulmonary bypass, followed 4 hours later by a postoperative infusion of 9 mg/(kg·h) continued up to 48 hours. Using this regimen, plasma arginine, citrulline, and nitric oxide metabolite levels were well maintained. Intravenous citrulline needs to be studied further as a potential therapy for postoperative pulmonary hypertension