4-H Animal Care as Therapy for At-Risk Youth

Encouraging nurturing traits through the interaction of animals and at-risk youth can help reduce antisocial behavior. A 4-H animal-care program was initiated at The Wyoming Girls School as part of the rehabilitation process for the School\u27s residents. Self-assessments by the young women indicated that the animals served a therapeutic role. Supervised interaction between at-risk youth and animals can provide an avenue to enhance self-esteem and build positive coping behaviors

First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children’s Oncology Group Phase 1/Pilot Consortium

Characterize the pharmacokinetics of oral crizotinib in children with cancer

Feasibility of pre-operative mTOR inhibitor Sirolimus in children and young adults with desmoid tumor

Background: • Desmoid tumor represents an intermediate grade neoplasm with a striking predilection for locally invasive growth and recurrence following resection • More effective, well-tolerated non-surgical treatment options are needed • Current approaches • If feasible, watchful waiting is the preferred approach • 20-30% spontaneous regression • In situations where treatment is indicated, the following approaches are utilized • Surgery is the primary approach if minimal morbidity is anticipated • Medical therapies • Cytotoxic drugs • Tyrosine kinase inhibitors • Hydroxyurea • Gamma secretase inhibitors • mTOR Inhibitor Rationale • Desmoid tumor is well-known to be associated with deregulation of the APC/β-catenin pathway • Deregulation of the mTOR cell proliferation/survival pathway may play an important role in tumor biology when the APC/βcatenin pathway is disrupted • The mTOR inhibitor sirolimus is attractive as a potential targeted therapy for desmoid tumor • Well-tolerated in children and young adults • Can be given orally in tablet or liquid formulatio

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents

PURPOSEThere is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders.METHODSAfter a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved.RESULTSCombinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements.CONCLUSIONAn optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer.</p

Bioavailability of Macro and Micronutrients Across Global Topsoils: Main Drivers and Global Change Impacts

Understanding the chemical composition of our planet\u27s crust was one of the biggest questions of the 20th century. More than 100 years later, we are still far from understanding the global patterns in the bioavailability and spatial coupling of elements in topsoils worldwide, despite their importance for the productivity and functioning of terrestrial ecosystems. Here, we measured the bioavailability and coupling of thirteen macro- and micronutrients and phytotoxic elements in topsoils (3–8 cm) from a range of terrestrial ecosystems across all continents (∼10,000 observations) and in response to global change manipulations (∼5,000 observations). For this, we incubated between 1 and 4 pairs of anionic and cationic exchange membranes per site for a mean period of 53 days. The most bioavailable elements (Ca, Mg, and K) were also amongst the most abundant in the crust. Patterns of bioavailability were biome-dependent and controlled by soil properties such as pH, organic matter content and texture, plant cover, and climate. However, global change simulations resulted in important alterations in the bioavailability of elements. Elements were highly coupled, and coupling was predictable by the atomic properties of elements, particularly mass, mass to charge ratio, and second ionization energy. Deviations from the predictable coupling-atomic mass relationship were attributed to global change and agriculture. Our work illustrates the tight links between the bioavailability and coupling of topsoil elements and environmental context, human activities, and atomic properties of elements, thus deeply enhancing our integrated understanding of the biogeochemical connections that underlie the productivity and functioning of terrestrial ecosystems in a changing world

Improving media competencies for teachers through in-service education

Photocopy of typescript.Digitized by Kansas Correctional Industrie

Prognostic Factors for Development of Subsequent Metastases in Localized Osteosarcoma: A Systematic Review and Identification of Literature Gaps

Aim. To investigate prognostic factors in pediatric and young adult patients with localized osteosarcoma that could predict the development of subsequent pulmonary metastases and lead to an ability to risk-stratify therapy. We performed a systematic review of the literature published since January 1990 to establish common evidence-based prognostic factors. Methods. PubMed and Embase searches (Jan 1990–Aug 2018) were performed. Two reviewers independently selected papers for patients with localized osteosarcoma with subsequent metastatic development and then reviewed for quality of methods and prognostic factors. Results. Database searches yielded 216 unique results. After screening, 27 full-text articles were studied in depth, with 9 items fulfilling predetermined inclusion and exclusion criteria. Age, tumor location, tumor size/volume, and histologic response carried independent prognostic value in the majority of the studies. Conclusions. Several prognostic factors seemed to be consistent amongst the studies, but the heterogeneity and smaller sizes of the study populations made pooling of results difficult. Standardization of larger patient populations and consistent definitions/cutoffs for prognostic factors are needed to further assess for consistent prognostic factors and potential predictive models to be developed

The Feasibility and Acceptability of a Data Capture Methodology in Pediatric Cancer Patients Treated with Targeted Agents and Immunotherapies

As childhood cancer treatments have improved to include new and innovative agents, the need for more advanced monitoring of their long-term effects and related research has increased. This has resulted in a need for evidence-based research methodologies for the longitudinal care of childhood cancer patients treated with targeted agents and immunotherapies. The rationale for this pilot study was to determine the feasibility and acceptability of a data capture methodology for pediatric, adolescent, and young adult cancer patients treated with targeted agents and immunotherapy as there is little research to inform this delivery of care. Data were collected from thirty-two patients and two providers for descriptive statistics and thematic analyses. Feasibility was characterized by expected participant attrition. Key drivers of acceptability were (1) providers’ language and clarity of communication and (2) convenient participation requirements. Long-term follow-up research practices developed with input from key stakeholders, including patients, caregivers, and providers, can lead to acceptable and feasible research protocols that optimize successful participant recruitment. These evidence-based research practices can result in high participant satisfaction and can be implemented as program development initiatives across centers caring for childhood cancer survivors