Characteristics of Children With Cancer Discharged or Admitted From the Emergency Department

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136395/1/pbc25872_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136395/2/pbc25872.pd

Characteristics of Children With Cancer Discharged or Admitted From the Emergency Department

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136395/1/pbc25872_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136395/2/pbc25872.pd

A televideo exercise and nutrition program for children with acute lymphoblastic leukemia in maintenance therapy: design and methods

Changes in nutrient intake and decreased exercise resulting from cancer therapies as well as their side effects may be contributing factors in the increased body weight and differences in physical fitness observed in survivors of childhood acute lymphoblastic leukemia (ALL). This article will describe the study protocol for an intervention program designed to improve the physical activity and nutrition behaviors of ALL survivors. Twenty-four children aged between 4 years and 12 years with ALL will be randomized to a 6-month technology-based exercise and nutrition program (TLC4ALLKids) or to enhanced usual care (eUC). The participants randomized to the TLC4ALLKids will participate in weekly, 1-hour coaching sessions on nutrition and physical activity and 1-hour physical activity classes delivered by group video conferencing. Participants will be provided with iPad tablets loaded with video conferencing software and the Healthy Lifestyle Tracking calendar to track daily nutrition and physical activity goals and weight. Both groups will be provided with Fitbit™ Zip to monitor physical activity. To assess feasibility, participant recruitment (achievement of proposed sample size), attendance (per weekly online sessions/assessment sessions), and adherence (number of families at 3 and 6 months) will be evaluated. Outcome measures to assess the intervention will include anthropometrics (weight, height, and waist circumference), physical activity (accelerometry), energy and macronutrient intake (food records), sleep habits (Children's Sleep Habits Questionnaire), and quality of life (Pediatric Quality of Life Inventory) will be obtained at baseline, 3 months, and 6 months. Semi-structured interviews will be used to gather information about ways to improve the program and overcome barriers to participation. If successful, the TLC4ALLKids intervention will provide a means to educate and improve the health behaviors of ALL survivors that can be delivered remotely and conveniently to participants

Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR

Metastasis is respoMetastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors

Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape

Prototype Testing Results of Charged Particle Detectors and Critical Subsystems for the ESRA Mission to GTO

The Experiment for Space Radiation Analysis (ESRA) is the latest of a series of Demonstration and Validation (DemVal) missions built by the Los Alamos National Laboratory, with the focus on testing a new generation of plasma and energetic paritcle sensors along with critical subsystems. The primary motivation for the ESRA payloads is to minimize size, weight, power, and cost while still providing necessary mission data. These new instruments will be demonstrated by ESRA through ground-based testing and on-orbit operations to increase their technology readiness level such that they can support the evolution of technology and mission objectives. This project will leverage a commercial off-the-shelf CubeSat avionics bus and commercial satellite ground networks to reduce the cost and timeline associated with traditional DemVal missions. The system will launch as a ride share with the DoD Space Test Program to be inserted in Geosynchronous Transfer Orbit (GTO) and allow observations of the Earth\u27s radiation belts. The ESRA CubeSat consists of two science payloads and several subsystems: the Wide field-of-view Plasma Spectrometer, the Energetic Charged Particle telescope, high voltage power supply, payload processor, flight software architecture, and distributed processor module. The ESRA CubeSat will provide measurements of the plasma and energetic charged particle populations in the GTO environment for ions ranging from ~100 eV to ~1000 MeV and electrons with energy ranging from 100 keV to 20 MeV. ESRA will utilize a commercial 12U bus and demonstrate a low-cost, rapidly deployable spaceflight platform with sufficient SWAP to enable efficient measurements of the charged particle populations in the dynamic radiation belts

Glastir Monitoring & Evaluation Programme. Second year annual report

What is the purpose of Glastir Monitoring and Evaluation Programme? Glastir is the main scheme by which the Welsh Government pays for environmental goods and services whilst the Glastir Monitoring and Evaluation Programme (GMEP) evaluates the scheme’s success. Commissioning of the monitoring programme in parallel with the launch of the Glastir scheme provides fast feedback and means payments can be modified to increase effectiveness. The Glastir scheme is jointly funded by the Welsh Government (through the Rural Development Plan) and the EU. GMEP will also support a wide range of other national and international reporting requirements. What is the GMEP approach? GMEP collects evidence for the 6 intended outcomes from the Glastir scheme which are focussed on climate change, water and soil quality, biodiversity, landscape, access and historic environment, woodland creation and management. Activities include; a national rolling monitoring programme of 1km squares; new analysis of long term data from other schemes combining with GMEP data where possible; modelling to estimate future outcomes so that adjustments can be made to maximise impact of payments; surveys to assess wider socio-economic benefits; and development of novel technologies to increase detection and efficiency of future assessments. How has GMEP progressed in this 2nd year? 90 GMEP squares were surveyed in Year 2 to add to the 60 completed in Year 1 resulting in 50% of the 300 GMEP survey squares now being completed. Squares will be revisited on a 4 year cycle providing evidence of change in response to Glastir and other pressures such as changing economics of the farm business, climate change and air pollution. This first survey cycle collects the baseline against which future changes will be assessed. This is important as GMEP work this year has demonstrated land coming into the scheme is different in some respects to land outside the scheme. Therefore, future analysis to detect impact of Glastir will be made both against the national backdrop from land outside the scheme and this baseline data from land in scheme. A wide range of analyses of longterm data has been completed for all Glastir Outcomes with the exception of landscape quality and historic features condition for which limited data is available. This has involved combining data with 2013/14 GMEP data when methods allow. Overall analysis of long term data indicates one of stability but with little evidence of improvement with the exception of headwater quality, greenhouse gas emissions and woodland area for which there has been improvement over the last 20 years. Some headline statistics include: 51% of historic features in excellent or sound condition; two thirds of public rights of way fully open and accessible; improvement in hedgerow management with 85% surveyed cut in the last 3 years but < 1% recently planted; 91% of streams had some level of modification but 60% retained good ecological quality; no change topsoil carbon content over last 25 years. What is innovative? GMEP has developed various new metrics to allow for more streamlined reporting in the future. For example a new Priority Bird species Index for Wales which combines data from 35 species indicates at least half have stable or increasing populations. The new GMEP Visual Quality Landscape Index has been tested involving over 2600 respondents. Results have demonstrated its value as an objective and repeatable method for quantifying change in visual landscape quality. A new unified peat map for Wales has been developed which has been passed to Glastir Contract Managers to improve targeting of payments when negotiating Glastir contracts. An estimate of peat soil contribution to current greenhouse gas emissions due to human modification has been calculated. Models have allowed quantification of land area helping to mitigate rainfall runoff. We are using new molecular tools to explore the effects of Glastir on soil organisms and satellite technologies to quantify e.g. small woody features and landcover change. Finally we are using a community approach to develop a consensus on how to define and report change in High Nature Value Farmland which will be reported in the Year 3 GMEP report

Glastir Monitoring & Evaluation Programme. First year annual report

The Welsh Government has commissioned a comprehensive new ecosystem monitoring and evaluation programme to monitor the effects of Glastir, its new land management scheme, and to monitor progress towards a range of international biodiversity and environmental targets. A random sample of 1 km squares stratified by landcover types will be used both to monitor change at a national level in the wider countryside and to provide a backdrop against which intervention measures are assessed using a second sample of 1 km squares located in areas eligible for enhanced payments for advanced interventions. Modelling in the first year has forecast change based on current understanding, whilst a rolling national monitoring programme based on an ecosystem approach will provide an evidence-base for on-going, adaptive development of the scheme by Welsh Government. To our knowledge, this will constitute the largest and most in-depth ecosystem monitoring and evaluation programme of any member state of the European Union

Searching for dark matter annihilation in recently discovered Milky Way satellites with Fermi-LAT

We search for excess γ-ray emission coincident with the positions of confirmed and candidate Milky Way satellite galaxies using six years of data from the Fermi Large Area Telescope (LAT). Our sample of 45 stellar systems includes 28 kinematically confirmed dark-matter-dominated dwarf spheroidal galaxies (dSphs) and 17 recently discovered systems that have photometric characteristics consistent with the population of known dSphs. For each of these targets, the relative predicted γ-ray flux due to dark matter annihilation is taken from kinematic analysis if available, and estimated from a distance-based scaling relation otherwise, assuming that the stellar systems are DM-dominated dSphs. LAT data coincident with four of the newly discovered targets show a slight preference (each ~2σ local) for γ-ray emission in excess of the background. However, the ensemble of derived γ-ray flux upper limits for individual targets is consistent with the expectation from analyzing random blank-sky regions, and a combined analysis of the population of stellar systems yields no globally significant excess (global significance 1 TeV and mDM,t+t-> 70 GeV) and weakening by a factor of ~1.5 at lower masses relative to previously observed limits

The Dark Energy Survey : more than dark energy – an overview

This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)