Exercise Prehabilitation during Neoadjuvant Cancer Treatment in Patients with Gastrointestinal and Thoracic Cancer: A Systematic Review

Abstract Aim: To evaluate the current evidence assessing the use of exercise prehabilitation interventions during neoadjuvant cancer treatment in those patients with gastrointestinal or thoracic cancer. Methods: A comprehensive and systematic database search was performed to identify all published clinical studies involving exercise prehabilitation during neoadjuvant cancer treatment for patients diagnosed with gastrointestinal or thoracic cancer. Pre-defined criteria were used to identify relevant articles and the Modified Downs and Black checklist was used for quality assessment purposes. Results: The search identified 508 relevant abstracts. After screening, 18 full-text articles were assessed for eligibility and inclusion. Three full-text articles met all the search criteria and were included in the review. Physical fitness was the main outcome measure and an improvement in physical fitness was observed in all three included studies. There was good adherence to the exercise programmes with a lack of associated adverse events, suggesting safety and feasibility of such interventions in this setting. A differentiation between ‘responders’ and ‘non-responders’ to exercise training was identified for the first time. Conclusions: This is the first systematic review assessing the use of exercise prehabilitation during neoadjuvant cancer treatment in patients with gastrointestinal and thoracic cancer. Although this review demonstrates the safe use of exercise prehabilitation during neoadjuvant cancer treatment in patients with gastrointestinal and thoracic cancer, there is still insufficient evidence to support any robust conclusions regarding the ideal characteristics of an exercise prehabilitation intervention and the impact it may have on clinical and post-operative outcomes. Keywords: Exercise prehabilitation; Oncology; Surgery; Neoadjuvant cancer treatment; Gastrointestinal; Thoraci

The Wnt Co-Receptor Lrp6 Is Required for Normal Mouse Mammary Gland Development

Canonical Wnt signals are transduced through a Frizzled receptor and either the LRP5 or LRP6 co-receptor; such signals play central roles during development and in disease. We have previously shown that Lrp5 is required for ductal stem cell activity and that loss of Lrp5 delays normal mammary development and Wnt1-induced tumorigenesis. Here we show that canonical Wnt signals through the Lrp6 co-receptor are also required for normal mouse mammary gland development. Loss of Lrp6 compromises Wnt/β-catenin signaling and interferes with mammary placode, fat pad, and branching development during embryogenesis. Heterozygosity for an inactivating mutation in Lrp6 is associated with a reduced number of terminal end buds and branches during postnatal development. While Lrp6 is expressed in both the basal and luminal mammary epithelium during embryogenesis, Lrp6 expression later becomes restricted to cells residing in the basal epithelial layer. Interestingly, these cells also express mammary stem cell markers. In humans, increased Lrp6 expression is associated with basal-like breast cancer. Taken together, our results suggest both overlapping and specific functions for Lrp5 and Lrp6 in the mammary gland

Addressing data integration challenges to link ecological processes across scales

Data integration is a statistical modeling approach that incorporates multiple data sources within a unified analytical framework. Macrosystems ecology – the study of ecological phenomena at broad scales, including interactions across scales – increasingly employs data integration techniques to expand the spatiotemporal scope of research and inferences, increase the precision of parameter estimates, and account for multiple sources of uncertainty in estimates of multiscale processes. We highlight four common analytical challenges to data integration in macrosystems ecology research: data scale mismatches, unbalanced data, sampling biases, and model development and assessment. We explain each problem, discuss current approaches to address the issue, and describe potential areas of research to overcome these hurdles. Use of data integration techniques has increased rapidly in recent years, and given the inferential value of such approaches, we expect continued development and wider application across ecological disciplines, especially in macrosystems ecology

Assessment of ion kinetic effects in shock-driven inertial confinement fusion implosions using fusion burn imaging

The significance and nature of ion kinetic effects in D3He-filled, shock-driven inertial confinement fusion implosions are assessed through measurements of fusion burn profiles. Over this series of experiments, the ratio of ion-ion mean free path to minimum shell radius (the Knudsen number, NK) was varied from 0.3 to 9 in order to probe hydrodynamic-like to strongly kinetic plasma conditions; as the Knudsen number increased, hydrodynamic models increasingly failed to match measured yields, while an empirically-tuned, first-step model of ion kinetic effects better captured the observed yield trends [Rosenberg et al., Phys. Rev. Lett. 112, 185001 (2014)]. Here, spatially resolved measurements of the fusion burn are used to examine kinetic ion transport effects in greater detail, adding an additional dimension of understanding that goes beyond zero-dimensional integrated quantities to one-dimensional profiles. In agreement with the previous findings, a comparison of measured and simulated burn profiles shows that models including ion transport effects are able to better match the experimental results. In implosions characterized by large Knudsen numbers (NK3), the fusion burn profiles predicted by hydrodynamics simulations that exclude ion mean free path effects are peaked far from the origin, in stark disagreement with the experimentally observed profiles, which are centrally peaked. In contrast, a hydrodynamics simulation that includes a model of ion diffusion is able to qualitatively match the measured profile shapes. Therefore, ion diffusion or diffusion-like processes are identified as a plausible explanation of the observed trends, though further refinement of the models is needed for a more complete and quantitative understanding of ion kinetic effects

Neutron time-of-flight measurements of charged-particle energy loss in inertial confinement fusion plasmas

Neutron spectra from secondary ^{3}H(d,n)α reactions produced by an implosion of a deuterium-gas capsule at the National Ignition Facility have been measured with order-of-magnitude improvements in statistics and resolution over past experiments. These new data and their sensitivity to the energy loss of fast tritons emitted from thermal ^{2}H(d,p)^{3}H reactions enable the first statistically significant investigation of charged-particle stopping via the emitted neutron spectrum. Radiation-hydrodynamic simulations, constrained to match a number of observables from the implosion, were used to predict the neutron spectra while employing two different energy loss models. This analysis represents the first test of stopping models under inertial confinement fusion conditions, covering plasma temperatures of k_{B}T≈1-4  keV and particle densities of n≈(12-2)×10^{24}  cm^{-3}. Under these conditions, we find significant deviations of our data from a theory employing classical collisions whereas the theory including quantum diffraction agrees with our data

Impact of asymmetries on fuel performance in inertial confinement fusion

Low-mode asymmetries prevent effective compression, confinement, and heating of the fuel in inertial confinement fusion (ICF) implosions, and their control is essential to achieving ignition. Ion temperatures (Tion) in ICF experiments are inferred from the broadening of primary neutron spectra. Directional motion (flow) of the fuel at burn also impacts broadening and will lead to artificially inflated "Tion" values. Flow due to low-mode asymmetries is expected to give rise to line-of-sight variations in measured Tion. We report on intentionally asymmetrically driven experiments at the OMEGA laser facility designed to test the ability to accurately predict and measure line-of-sight differences in apparent Tion due to low-mode asymmetry-seeded flows. Contrasted to chimera and xrage simulations, the measurements demonstrate how all asymmetry seeds have to be considered to fully capture the flow field in an implosion. In particular, flow induced by the stalk that holds the target is found to interfere with the seeded asymmetry. A substantial stalk-seeded asymmetry in the areal density of the implosion is also observed

Measurement of Charged-Particle Stopping in Warm Dense Plasma

We measured the stopping of energetic protons in an isochorically heated solid-density Be plasma with an electron temperature of ~32  eV, corresponding to moderately coupled [(e[superscript 2]/a)/(k[subscript B]T[subscript e] + E[subscript F]) ~ 0.3] and moderately degenerate [k[subscript B]T[subscript e]/E[subscript F] ~ 2] “warm-dense matter” (WDM) conditions. We present the first high-accuracy measurements of charged-particle energy loss through dense plasma, which shows an increased loss relative to cold matter, consistent with a reduced mean ionization potential. The data agree with stopping models based on an ad hoc treatment of free and bound electrons, as well as the average-atom local-density approximation; this work is the first test of these theories in WDM plasma.United States. Dept. of Energy (Grant DE-NA0001857)United States. Dept. of Energy (Grant DE-FC52-08NA28752)Lawrence Livermore National Laboratory (Grant B597367)University of Rochester. Laboratory for Laser Energetics (Grant 415935-G)University of Rochester. Fusion Science Center (Grant 524431)National Laser User’s Facility (Grant DE-NA0002035)National Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374