A Survey of Music Therapists Working in Pediatric Medical Settings in the United States

Music therapy is becoming a standard supportive care service in many pediatric hospitals across the United States. However, more detailed information is needed to advance our understanding about current clinical practice and increase availability of pediatric music therapy services. The purpose of this cross-sectional survey study was to collect and summarize data about music therapists working in pediatric medical settings. Specifically, we collected information about (1) therapist demographics, (2) organizational structure, (3) service delivery and clinical practice, and (4) administrative/supervisory responsibilities. Board-certified music therapists working in pediatric medical settings (n = 118) completed a 37-item online questionnaire. We analyzed survey data using descriptive statistics and content analysis. Findings indicated that there is a ratio of approximately one music therapist for every 100 patient beds, that one-third of respondents are the only music therapist in their setting, and that half of the surveyed positions are philanthropically funded. Prioritizing patient referrals based on acuity was common (95.7%, n = 110), with palliative care and pain as the most highly prioritized needs. More than half of respondents reported serving in high acuity areas such as the pediatric intensive care, hematology/oncology, or neonatal intensive care units. We recommend replication of this survey in five years to examine growth and change in service delivery among pediatric music therapists over time, with additional studies to (a) explore how therapist-to-patient ratios influence quality of care, (b) identify factors that contribute to sustainability of programs, and (c) determine how expansion of services support a broader population of patients and families

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion. We developed a multiparametric in situ immunofluorescence staining to identify and quantify at the cellular level the co-expression of these inhibitory receptors. On a retrospective series of frozen tissue of renal cell carcinomas (RCC), using a fluorescence multispectral imaging technology coupled with an image analysis software, it was found that co-expression of PD-1 and Tim-3 on tumor infiltrating CD8 T cells is correlated with a poor prognosis in RCC. To our knowledge, this represents the first study demonstrating that this automated multiplex in situ technology may have some clinical relevance

Qualification and characterization of electronics of the fast neutron Hodoscope detectors using neutrons from CABRI core

The study of Reactivity Initiated Accidents (RIA) is important to determine up to which limits nuclear fuels can withstand such accidents without clad failure. The CABRI International Program (CIP), conducted by IRSN under an OECD/NEA agreement, has been launched to perform representative RIA Integral Effect Tests (IET) on real irradiated fuel rods in prototypical Pressurized Water Reactors (PWR) conditions. For this purpose, the CABRI experimental pulse reactor, operated by CEA in Cadarache, France, has been strongly renovated, and equipped with a pressurized water loop. The behavior of the test rod, located in that loop in the center of the driver core, is followed in real time during the power transients thanks to the hodoscope, a unique online fuel motion monitoring system, and one of the major distinctive features of CABRI. The hodoscope measures the fast neutrons emitted by the tested rod during the power pulse with a complete set of 153 Fission Chambers and 153 Proton Recoil Counters. During the CABRI facility renovation, the electronic chain of these detectors has been upgraded. In this paper, the performance of the new system is presented describing gain calibration methodology in order to get maximal Signal/Noise ratio for amplification modules, threshold tuning methodology for the discrimination modules (old and new ones), and linear detectors response limit versus different reactor powers for the whole electronic chain

Rad51 and DNA-PKcs are involved in the generation of specific telomere aberrations induced by the quadruplex ligand 360A that impair mitotic cell progression and lead to cell death

Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways. Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands. NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting by the G-quadruplex ligand 360A, leading to cancer cell death

The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation

Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro-irradiated Cdk5KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5-dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels

The CABRI fast neutron Hodoscope: Renovation, qualification program and first results following the experimental reactor restart

The CABRI experimental pulse reactor, located at the Cadarache nuclear research center, southern France, is devoted to the study of Reactivity Initiated Accidents (RIA). For the purpose of the CABRI International Program (CIP), managed and funded by IRSN, in the framework of an OECD/NEA agreement, a huge renovation of the facility has been conducted since 2003. The Cabri Water Loop was then installed to ensure prototypical Pressurized Water Reactor (PWR) conditions for testing irradiated fuel rods. The hodoscope installed in the CABRI reactor is a unique online fuel motion monitoring system, operated by IRSN and dedicated to the measurement of the fast neutrons emitted by the tested rod during the power pulse. It is one of the distinctive features of the CABRI reactor facility, which is operated by CEA. The system is able to determine the fuel motion, if any, with a time resolution of 1 ms and a spatial resolution of 3 mm. The hodoscope equipment has been upgraded as well during the CABRI facility renovation. This paper presents the main outcomes achieved with the hodoscope since October 2015, date of the first criticality of the CABRI reactor in its new Cabri Water Loop configuration. Results obtained during reactor commissioning phase functioning, either in steady-state mode (at low and high power, up to 23 MW) or in transient mode (start-up, possibly beyond 20 GW), are discussed

Novel Anti-Metastatic Action of Cidofovir Mediated by Inhibition of E6/E7, CXCR4 and Rho/ROCK Signaling in HPV+ Tumor Cells

Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1α and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1α/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1α stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1) in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo) cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1α/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1α-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion) supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1α/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor). These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition