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Abstract As the incidence of cancer continues to rise, the use of radiotherapy has emerged as a leading treatment modality. Preclinical models in radiation oncology are essential tools for cancer research and therapeutics. Various model systems have been used to test radiation therapy, including in vitro cell culture assays as well as in vivo ectopic and orthotopic xenograft models. This review aims to describe such models, their advantages and disadvantages, particularly as they have been employed in the discovery of molecular targets for tumor radiosensitization. Ultimately, any model system must be judged by its utility in developing more effective cancer therapies, which is in turn dependent on its ability to simulate the biology of tumors as they exist in situ. Although every model has its limitations, each has played a significant role in preclinical testing. Continued advances in preclinical models will allow for the identification and application of targets for radiation in the clinic.

Abstract Background The Awareness program was designed as a part of the EU-funded Saving and Empowering Young Lives in Europe (SEYLE) intervention study to promote mental health of adolescents in 11 European countries by helping them to develop problem-solving skills and encouraging them to self-recognize the need for help as well as how to help peers in need. Methods For this descriptive study all coordinators of the SEYLE Awareness program answered an open-ended evaluation questionnaire at the end of the project implementation. Their answers were synthesized and analyzed and are presented here. Results The results show that the program cultivated peer understanding and support. Adolescents not only learned about mental health by participating in the Awareness program, but the majority of them also greatly enjoyed the experience. Conclusions Recommendations for enhancing the successes of mental health awareness programs are presented. Help and cooperation from schools, teachers, local politicians and other stakeholders will lead to more efficacious future programs.

Abstract Background Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and young children. During each seasonal epidemic, multiple strains of both subgroup A and B viruses circulate in the community. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines IL-6 and CCL5 (previously known as RANTES [regulated upon activation, normal T-cell expressed and secreted protein]), which are known to be induced in vitro and in vivo in response to RSV, during infection of A549 cells. Results Screening of subgroup A and B isolates revealed heterogeneity among strains to induce IL-6 and CCL5. We chose two subgroup B strains, New Haven (NH)1067 and NH1125, for further analysis because of their marked differences in cytokine inducing properties and because subgroup B strains, in general, are less genetically heterogeneous as compared to subgroup A strains. At 12 and 24 hours post infection RSV strains, NH1067 and NH1125 differed in their capacity to induce IL-6 by an order of magnitude or more. The concentrations of IL-6 and CCL5 were dependent on the dose of infectious virus and the concentration of these cytokines induced by NH1125 was greater than that of those induced by NH1067 when the multiplicity of infection of NH1067 used was as much as 10-fold higher than that of NH1125. The induction of IL-6 was dependent on viable virus as infection with UV-inactivated virus did not induce IL-6. The difference in IL-6 induction most likely could not be explained by differences in viral replication kinetics. The intracellular level of RSV RNA, as determined by quantitative RT-PCR, was indistinguishable between the 2 strains though the titer of progeny virus produced by NH1125 was greater than that produced by NH1067 at 16, 24 and 36 hours but essentially equal at 48 and 72 hours. Full genome sequencing of the 2 strains revealed 193 polymorphisms and 4 insertions in NH1067when compared to NH1125 (2 single base insertions in non-coding regions and 2 duplications of 3 and 60 bases in the RSV G gene). Of the polymorphisms, 147 occurred in coding regions and only 30 resulted in amino acid changes in 7 of the RSV genes. Conclusions These data suggest that RSV strains may not be homogeneous with regard to pathogenesis or virulence. Identification of the genetic polymorphisms associated with variations in cytokine induction may lead to insights into RSV disease and to the development of effective antiviral agents and vaccines.

Abstract Background Long-term acute care hospitals (LTACs) provide specialized care for patients recovering from severe acute illness. In order to facilitate research into LTAC utilization and outcomes, we studied whether or not the discharge destination field in administrative data accurately identifies patients transferred to an LTAC following acute care hospitalization. Findings We used the 2006 hospitalization claims for United States Medicare beneficiaries to examine the performance characteristics of the discharge destination field in the administrative record, compared to the reference standard of directly observing LTAC transfers in the claims. We found that the discharge destination field was highly specific (99.7%, 95 percent CI: 99.7% - 99.8%) but modestly sensitive (77.3%, 95 percent CI: 77.0% - 77.6%), with corresponding low positive predictive value (72.6%, 95 percent CI: 72.3% - 72.9%) and high negative predictive value (99.8%, 95 percent CI: 99.8% - 99.8%). Sensitivity and specificity were similar when limiting the analysis to only intensive care unit patients and mechanically ventilated patients, two groups with higher rates of LTAC utilization. Performance characteristics were slightly better when limiting the analysis to Pennsylvania, a state with relatively high LTAC penetration. Conclusions The discharge destination field in administrative data can result in misclassification when used to identify patients transferred to long-term acute care hospitals. Directly observing transfers in the claims is the preferable method, although this approach is only feasible in identified data.

Abstract Background There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior, and, in most of those studies, the target populations were primarily adults, whereas few focused on adolescents. Essentially, there have been no randomized controlled studies comparing the efficacy, cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools. There is also a lack of information on whether suicide-preventive interventions can, in addition to preventing suicide, reduce risk behaviors and promote healthier ones as well as improve young people's mental health. The aim of the SEYLE project, which is funded by the European Union under the Seventh Framework Health Program, is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological database; testing, in a randomized controlled trial, three different suicide-preventive interventions; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors. Methods and design The study comprises 11,000 adolescents emitted from randomized schools in 11 European countries: Austria, Estonia, France, Germany, Hungary, Ireland, Israel, Italy, Romania, Slovenia and Spain, with Sweden serving as the scientific coordinating center. Each country performs three active interventions and one minimal intervention as a control group. The active interventions include gatekeeper training (QPR), awareness training on mental health promotion for adolescents, and screening for at-risk adolescents by health professionals. Structured questionnaires are utilized at baseline, 3- and 12-month follow-ups in order to assess changes. Discussion Although it has been reported that suicide-preventive interventions can be effective in decreasing suicidal behavior, well-documented and randomized studies are lacking. The effects of such interventions in terms of combating unhealthy lifestyles in young people, which often characterize suicidal individuals, have never been reported. We know that unhealthy and risk-taking behaviors are detrimental to individuals' current and future health. It is, therefore, crucial to test well-designed, longitudinal mental health-promoting and suicide-preventive interventions by evaluating the implications of such activities for reducing unhealthy and risk behaviors while concurrently promoting healthy ones. Trial registration The German Clinical Trials Register, DRKS00000214.

Abstract Background Regionalization of adult critical care services may improve outcomes for critically ill patients. We sought to develop a framework for understanding clinician attitudes toward regionalization and potential barriers to developing a tiered, regionalized system of care in the United States. Methods We performed a qualitative study using semi-structured interviews of critical care stakeholders in the United States, including physicians, nurses and hospital administrators. Stakeholders were identified from a stratified-random sample of United States general medical and surgical hospitals. Key barriers and potential solutions were identified by performing content analysis of the interview transcriptions. Results We interviewed 30 stakeholders from 24 different hospitals, representing a broad range of hospital locations and sizes. Key barriers to regionalization included personal and economic strain on families, loss of autonomy on the part of referring physicians and hospitals, loss of revenue on the part of referring physicians and hospitals, the potential to worsen outcomes at small hospitals by limiting services, and the potential to overwhelm large hospitals. Improving communication between destination and source hospitals, provider education, instituting voluntary objective criteria to become a designated referral center, and mechanisms to feed back patients and revenue to source hospitals were identified as potential solutions to some of these barriers. Conclusion Regionalization efforts will be met with significant conceptual and structural barriers. These data provide a foundation for future research and can be used to inform policy decisions regarding the design and implementation of a regionalized system of critical care.