Citations

This article describes our shared expertise and collaborative efforts to develop guidelines and recommendations for subspecialized training in pediatric pain psychology. First, we review the competency goals and standards relevant to subspecialized training in pediatric pain psychology. Next, we detail our shared understanding of competencies in pediatric pain psychology and the training experiences to foster their development. Third, we highlight collaborative activities of our subspecialized training programs in order to demonstrate ways each program can optimize training curriculum. We conclude with a reflection of the current state of subspecialized training, directions for further development, and implications for other subspecialty programs.

AbstractSingle‐isocenter, multitarget cranial stereotactic radiosurgery (SRS) is more efficient than using an isocenter for each target, but spatial positioning uncertainties can be magnified at locations away from the isocenter. This study reports on the spatial accuracy of two frameless, linac‐based SRS systems for multitarget, single‐isocenter SRS as a function of distance from the isocenter. One system uses the ExacTrac platform for image guidance and the other localizes with cone beam computed tomography (CBCT). For each platform, a phantom with 12 target BBs distributed up to 13.8 cm from the isocenter was aligned starting from five different initial offsets and then imaged with the treatment beam at seven different gantry and couch angles. The distribution of the resulting positioning errors demonstrated the value of adding a 1‐mm PTV margin for targets up to about 7–8 cm from the isocenter. For distances 10 cm or more, the CBCT‐based alignment remained within 1.1 mm while the ExacTrac‐based alignment differed by up to 2.2 mm.

Abstract Quantitative evaluation of passive tension in a muscle is important in tendon transfer surgeries, however, currently appropriate intraoperative measurement techniques are lacking. Objective : Intramuscular pressure (IMP) is explored as an application to access force. Approach : The tibialis anterior (TA) in New Zealand white rabbits ( n = 9) was used to test the hypothesis of a strong correlation between the IMP, muscle force, and length. This study also helped to develop intraoperative techniques for future human studies evaluating various insertion techniques (parallel versus perpendicular). Main results : The Pearson correlation between IMP and force for all trials was 0.74 ± 0.30. Separating out the parallel insertion from the perpendicular insertion revealed a significantly higher correlation for parallel, 0.91 ± 0.13 versus 0.56 ± 0.32. Significance : These data indicate IMP sensors can be used to assess force in a single muscle and the parallel insertion method should be used. New findings • What is the central question of this study? Successful outcomes of tendon and muscle transfers depend on proper muscle tension. A near linear relationship has been seen between muscle force and intramuscular pressure. This study aims to develop an intraoperative technique for assessing passive muscle tension using intramuscular pressure. • What is the main finding and its importance? The findings from this study reveal a high correlation between pressure and passive tension in a single muscle. The techniques developed in this study will allow the translation to a human model. The work will help to improve surgical outcomes and aim to retain muscle strength in the patient following procedures such as tendon and muscle transfers.

Abstract Aims High-intensity interval training (HIIT) improves peak oxygen uptake and left ventricular diastology in patients with heart failure with preserved ejection fraction (HFpEF). However, its effects on myocardial strain in HFpEF remain unknown. We explored the effects of HIIT and moderate-intensity aerobic continuous training (MI-ACT) on left and right ventricular strain parameters in patients with HFpEF. Furthermore, we explored their relationship with peak oxygen uptake (VO2peak). Methods and results Fifteen patients with HFpEF (age = 70 ± 8.3 years) were randomized to either: (i) HIIT (4 × 4 min, 85–90% peak heart rate, interspersed with 3 min of active recovery; n = 9) or (ii) MI-ACT (30 min at 70% peak heart rate; n = 6). Patients were trained 3 days/week for 4 weeks and underwent VO2peak testing and 2D echocardiography at baseline and after completion of the 12 sessions of supervised exercise training. Left ventricular (LV) and right ventricular (RV) average global peak systolic longitudinal strain (GLS) and peak systolic longitudinal strain rate (GSR) were quantified. Paired t-tests were used to examine within-group differences and unpaired t-tests used for between-group differences (α = 0.05). Right ventricular average global peak systolic longitudinal strain improved significantly in the HIIT group after training (pre = −18.4 ± 3.2%, post = −21.4 ± 1.7%; P = 0.02) while RV-GSR, LV-GLS, and LV-GSR did not (P > 0.2). No significant improvements were observed following MI-ACT. No significant between-group differences were observed for any strain measure. ΔLV-GLS and ΔRV-GLS were modestly correlated with ΔVO2peak (r = −0.48 and r = −0.45; P = 0.1, respectively). Conclusions In patients with HFpEF, 4 weeks of HIIT significantly improved RV-GLS.

Background: Currently, glycemic management for individuals with diabetes mellitus involves monitoring glucose only, which is insufficient as glucose metabolism involves other biomarkers such as insulin. Monitoring additional biomarkers alongside glucose has been proposed to improve glycemic control. In this work, the development of a rapid and label-free insulin biosensor with high sensitivity and accuracy is presented. The insulin sensor prototype also serves as a prior study for a multimarker sensing platform technology that can further improve glycemic control in the future. Methods: Electrochemical impedance spectroscopy was used to identify an optimal frequency specific to insulin detection on a gold disk electrode with insulin antibody immobilized, which was accomplished by conjugating the primary amines of insulin antibody to the carboxylic bond of the self-assembling monolayer on the gold surface. After blocking with ethanolamine, the insulin physiological concentration gradient was tested. The imaginary impedance was correlated to insulin concentration and the results were compared with standard equivalent circuit analysis and correlation of charge transfer resistance to target concentration. Results: The optimal frequency of insulin is 810.5 Hz, which is characterized by having the highest sensitivity and sufficient specificity. The lower limit of detection was 2.26 ρ M which is comparable to a standard and better than traditional approaches. Conclusion: An insulin biosensor prototype capable of detecting insulin in physiological range without complex data normalization was developed. This prototype will be the ground works of a multimarker platform sensor technology for future all-in-one glycemic management sensors.

Abstract Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-type lectin (Mincle) for host defense against Pneumocystis. Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels. Mouse macrophages overexpressing Mincle displayed increased binding to P. carinii life forms and enhanced protein tyrosine phosphorylation. The binding of P. carinii to Mincle resulted in activation of FcRγ-mediated cell signaling. RNA silencing of Mincle in mouse macrophages resulted in decreased activation of Syk kinase after P. carinii challenge, critical in downstream inflammatory signaling. Mincle-deficient CD4-depleted (Mincle−/−) mice showed a significant defect in organism clearance from the lungs with higher organism burdens and altered lung cytokine responses during Pneumocystis murina pneumonia. Interestingly, Mincle−/− mice did not demonstrate worsened survival during PCP compared with wild-type mice, despite the markedly increased organism burdens. This may be related to increased expression of anti-inflammatory factors such as IL-1Ra during infection in the Mincle−/− mice. Of note, the P. murina–infected Mincle−/− mice demonstrated increased expression of known C-type lectin receptors Dectin-1, Dectin-2, and MCL compared with infected wild-type mice. Taken together, these data support a significant role for Mincle in Pneumocystis modulating host defense during infection.

AbstractHomologous recombination (HR) DNA repair‐deficient (HRD) breast cancers have been shown to be sensitive to DNA repair targeted therapies. Burgeoning evidence suggests that sporadic breast cancers, lacking germline BRCA1/BRCA2 mutations, may also be HRD. We developed a functional ex vivo RAD51‐based test to identify HRD primary breast cancers. An integrated approach examining methylation, gene expression, and whole‐exome sequencing was employed to ascertain the aetiology of HRD. Functional HRD breast cancers displayed genomic features of lack of competent HR, including large‐scale state transitions and specific mutational signatures. Somatic and/or germline genetic alterations resulting in bi‐allelic loss‐of‐function of HR genes underpinned functional HRD in 89% of cases, and were observed in only one of the 15 HR‐proficient samples tested. These findings indicate the importance of a comprehensive genetic assessment of bi‐allelic alterations in the HR pathway to deliver a precision medicine‐based approach to select patients for therapies targeting tumour‐specific DNA repair defects. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.