Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BackgroundFew adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).MethodsUsing AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.ResultsOverall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P < .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P < .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively).ConclusionNot only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed

Tissue Doppler imaging following paediatric cardiac surgery : early patterns of change and relationship to outcome

In this study, tissue Doppler imaging (TDI) was used to assess changes in ventricular function following repair of congenital heart defects. The relationship between TDI indices, myocardial injury and clinical outcome was explored. Forty-five children were studied; 35 withcardiac lesions and 10 controls. TDI was performed preoperatively, on admission to paediatric intensive care unit (PICU) and day 1. Regional myocardial Doppler signals were acquired from the right ventricle (RV), left ventricle (LV) and septum. TDI indices included: peak systolicvelocities, isovolumetric velocities (IVV) and isovolumetric acceleration (IVA). Preoperatively, bi-ventricular TDI velocities in the study groupwere reduced compared with normal controls. Postoperatively, RV velocities were significantly reduced and this persisted to day-1 (PreOp vs. PICU and day-1: 7.7+2.2 vs. 3.4+1.0, P < 0.0001 and 3.55+1.29, P < 0.0001). LV velocities initially declined but recovered towards baseline by day-1 (PreOp vs. PICU: 5.31+1.50 vs. 3.51+1.23, P < 0.0001). Isovolumetric parameters in all regions were reduced throughout the postoperative period. Troponin-I release correlated with longer X-clamp times (r=0.82, P < 0.0001) and reduced RV velocities (r=0.42, P=0.028). Reduced pre- and postoperative LV velocities correlated with longer ventilation (PreOp: r=0.54, P=0.002; PostOp: r=0.42, P=0.026). This study identified reduced postoperative RV velocities correlated with myocardial injury while reduced LV TDI correlated with longer postoperative ventilation

DMSO-free methods of preserving mesenchymal stem cells (MSCs) that retain high levels of post thaw function

A novel, biologically-inspired strategy was developed to improve the preservation of mesenchymal stem cells (MSCs). MSCs are being investigated for the treatment of cardiovascular disorders, diabetes, connective tissue disorders, acute lung injury, amyotrophic lateral sclerosis, kidney diseases and more. To date, over 300 clinical trials involve the use of MSCs, with well over 2000 patients safely treated.Current methods of preserving MSCs are inadequate/ suboptimal. Concerns over poor post thaw function have become so pervasive that it is now common for MSCs to be cultured for 24-72 h prior to administration. These MSCs have a short shelf life (\u3c 24 hours), require special FDA permission, and the process increases cost and reduces access. The research described here utilizes an evolutionary algorithm to identify combinations of naturally occurring osmolytes that yield high cell recovery post thaw and optimize the composition of a DMSO-free, protein-free medium for cryopreservation of the cells. Additionally, we demonstrate that these novel solutions maintain MSC functionality when evaluated using surface markers, attachment, proliferation, actin alignment, RNA expression, and DNA hydroxymethlyation. Please click Additional Files below to see the full abstract

Path integral Monte Carlo simulation of helium at negative pressures

Path integral Monte Carlo (PIMC) simulations of liquid helium at negative pressure have been carried out for a temperature range from the critical temperature to below the superfluid transition. We have calculated the temperature dependence of the spinodal line as well as the pressure dependence of the isothermal sound velocity in the region of the spinodal. We discuss the slope of the superfluid transition line and the shape of the dispersion curve at negative pressures.Comment: 6 pages, 7 figures, submitted to Physical Review B Revised: new reference, replaced figure

Towards the development of new subtype-specific muscarinic receptor radiopharmaceuticals-radiosynthesis and ex vivo biodistribution of [18F] 3-(4-(2-(2-(2-fluoroethoxy) ethoxy) ethylthio)-1, 2, 5-thiadiazol-3-yl)-1-methyl-1, 2, 5, 6-tetrahydropyridine

Muscarinic receptors have been implicated in neurological disorders including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Nineteen derivatives of thiadiazolyltetrahydropyridine (TZTP), a core that has previously shown high affinities towards muscarinic receptor subtypes, were synthesized and evaluated via in vitro binding assays. The title compound, a fluoro-polyethyleneglycol analog of TZTP (4c), was subsequently labelled with fluorine-18. Fluorine-18-labelled 4c was produced, via an automated synthesis, in an average radiochemical yield of 36% (uncorrected for decay), with high radiochemical purity (>99%) and high specific activity (326 GBq/µmol; end-of-bombardment), within 40 min (n = 3). Ex vivo biodistribution studies following tail-vein injection of [18F]4c in conscious rats displayed sufficient brain uptake (0.4%–0.7% injected dose / gram of wet tissue in all brain regions at 5 min post injection); however, there were substantial polar metabolites present in the brain, thereby precluding future use of [18F]4c for imaging in the central nervous system.peer-reviewe

The Lantern Vol. 31, No. 1, December 1963

• Today\u27s Memory • The Realization • Life Fire • Come Sleep • The Ends Meet • Dawn of Darkness • Closed and Done: With Apologies to No One • A Search • Concern • Obvious Oblivion • Love\u27s Ashes • Silence • To My Dentist • Snow • Wisdom • Look Up • Nepenthe • With Apologies to Charles Schulz • Autumn and You • What is Optimism? • Agnostic? • Potpourri of Beinghttps://digitalcommons.ursinus.edu/lantern/1085/thumbnail.jp

Thoracic Surgeons’ Beliefs and Practices on Smoking Cessation Before Lung Resection

BackgroundSmoking is a risk factor for complications after lung resection. Our primary aim was to ascertain thoracic surgeons' beliefs and practices on smoking cessation before lung resection.MethodsAn anonymous survey was emailed to 846 thoracic surgeons who participate in The Society of Thoracic Surgeons General Thoracic Surgery Database.ResultsThe response rate was 23.6% (n = 200). Surgeons were divided when asked whether it is ethical to require that patients quit smoking (yes, n = 96 [48%]) and whether it is fair to have their outcomes affected by patients who do not quit (yes, n = 87 [43.5%]). Most do not require smoking cessation (n = 120 [60%]). Of those who require it, the most common required period of cessation is 2 weeks or more. Most believe that patient factors are the main barrier to quitting (n = 160 [80%]). Risk of disease progression (39% vs 17.5%, p = 0.02) and alienating patients (17.5% vs 8.8%, p = 0.04) were very important considerations of those who do not require smoking cessation versus those who do. Only 19 (9.5%) always refer to a smoking cessation program and prescribe nicotine replacement therapy and even fewer, 9 (4.5%), always refer to a program and prescribe medical therapy.ConclusionsThoracic surgeons are divided on their beliefs and practices regarding smoking cessation before lung resection. Most believe patient factors are the main barrier to quitting and have concerns about disease progression while awaiting cessation. Very few surgeons refer to a smoking cessation program and prescribe nicotine replacement therapy or medical therapy

Albuminuria Is Associated with Endothelial Dysfunction and Elevated Plasma Endothelin-1 in Sickle Cell Anemia

The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables (vascular endothelial growth factor [VEGF], endothelin-1 [ET-1], soluble fms-like tyrosine kinase-1 [sFLT-1], soluble vascular cell adhesion molecule-1 [soluble VCAM-1] and plasma hemoglobin)

Relativistic mean-field study of neutron-rich nuclei

A relativistic mean-field model is used to study the ground-state properties of neutron-rich nuclei. Nonlinear isoscalar-isovector terms, unconstrained by present day phenomenology, are added to the model Lagrangian in order to modify the poorly known density dependence of the symmetry energy. These new terms soften the symmetry energy and reshape the theoretical neutron drip line without compromising the agreement with existing ground-state information. A strong correlation between the neutron radius of 208Pb and the binding energy of valence orbitals is found: the smaller the neutron radius of 208Pb, the weaker the binding energy of the last occupied neutron orbital. Thus, models with the softest symmetry energy are the first ones to drip neutrons. Further, in anticipation of the upcoming one-percent measurement of the neutron radius of 208Pb at the Thomas Jefferson Laboratory, a close relationship between the neutron radius of 208Pb and neutron radii of elements of relevance to atomic parity-violating experiments is established.Comment: 14 pages, 5 figure

Dopamine D2/3 occupancy of ziprasidone across a day : a within-subject PET study

Rationale Ziprasidone is an atypical antipsychotic recommended to be administered twice daily. Objectives The purpose of this study was to investigate whether occupancy of the dopamine D2/3 receptors by ziprasidone is maintained across a day employing a within subject design. Methods Positron emission tomography (PET) scans with [11C]-raclopride were performed in 12 patients with schizophrenia while treated with ziprasidone 60 mg twice daily. Each patient completed [11C]-raclopride PET scans at 5, 13 and 23 h after the last dose of ziprasidone. Dopamine D2/3 receptor occupancy was estimated with reference to binding potential data of 44 age- and sex-matched control subjects in the caudate, putamen and ventral striatum. Results Eleven scans were available at each time point, and the mean occupancies at 5-, 13- and 23-h scans were 66, 39 and 2 % in the putamen; 62, 35 and −6 % in the caudate; and 68, 47 and 11 % in the ventral striatum, respectively. The time-course of receptor occupancy across the regions indicated an occupancy half-life of 8.3 h. The serum level of ziprasidone associated with 50 % D2/3 receptors occupancy was estimated to be 204 nmol/L (84 ng/ml). Prolactin levels were highest at 5-h post-dose and none showed hyperprolactinemia at 23-h scans. Conclusions The absence of ziprasidone striatal D2/3 receptor binding 23 h after taking 60 mg under steady-state conditions is consistent with its peripheral half-life. The results support our earlier report that ziprasidone 60 mg administered twice daily appears to be the minimal dose expected to achieve therapeutic central dopamine D2/3 receptor occupancy (i.e. 60 %).peer-reviewe