The dynamics of energetic particles in strong electromagnetic fields can be heavily influenced by the energy loss arising from the emission of radiation during acceleration, known as radiation ...reaction. When interacting with a high-energy electron beam, today’s lasers are sufficiently intense to explore the transition between the classical and quantum radiation reaction regimes. We present evidence of radiation reaction in the collision of an ultrarelativistic electron beam generated by laser-wakefield acceleration (ϵ>500MeV) with an intense laser pulse (a0>10). We measure an energy loss in the postcollision electron spectrum that is correlated with the detected signal of hard photons (γrays), consistent with a quantum description of radiation reaction. The generatedγrays have the highest energies yet reported from an all-optical inverse Compton scattering scheme, with critical energyϵcrit>30MeV.
Recent advances in molecular simulations have allowed scientists to investigate slower biological processes than ever before. Together with these advances came an explosion of data that has ...transformed a traditionally computing-bound into a data-bound problem. Here, we present HTMD, a programmable, extensible platform written in Python that aims to solve the data generation and analysis problem as well as increase reproducibility by providing a complete workspace for simulation-based discovery. So far, HTMD includes system building for CHARMM and AMBER force fields, projection methods, clustering, molecular simulation production, adaptive sampling, an Amazon cloud interface, Markov state models, and visualization. As a result, a single, short HTMD script can lead from a PDB structure to useful quantities such as relaxation time scales, equilibrium populations, metastable conformations, and kinetic rates. In this paper, we focus on the adaptive sampling and Markov state modeling features.
We provide an evidence base and guidance for the use of menopausal hormone therapy (MHT) for the maintenance of skeletal health and prevention of future fractures in recently menopausal women. ...Despite controversy over associated side effects, which has limited its use in recent decades, the potential role for MHT soon after menopause in the management of postmenopausal osteoporosis is increasingly recognized. We present a narrative review of the benefits versus risks of using MHT in the management of postmenopausal osteoporosis. Current literature suggests robust anti-fracture efficacy of MHT in patients unselected for low BMD, regardless of concomitant use with progestogens, but with limited evidence of persisting skeletal benefits following cessation of therapy. Side effects include cardiovascular events, thromboembolic disease, stroke and breast cancer, but the benefit-risk profile differs according to the use of opposed versus unopposed oestrogens, type of oestrogen/progestogen, dose and route of delivery and, for cardiovascular events, timing of MHT use. Overall, the benefit-risk profile supports MHT treatment in women who have recently (< 10 years) become menopausal, who have menopausal symptoms and who are less than 60 years old, with a low baseline risk for adverse events. MHT should be considered as an option for the maintenance of skeletal health in women, specifically as an additional benefit in the context of treatment of menopausal symptoms, when commenced at the menopause, or shortly thereafter, in the context of a personalized benefit-risk evaluation.
Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different ...weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PI
) that maximized discrimination of the predictive model. Patients with higher PI
have higher predicted relapse risk. The PI
reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PI
identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PI
identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PI
identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PI
can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.
The high arithmetic performance and intrinsic parallelism of recent graphical processing units (GPUs) can offer a technological edge for molecular dynamics simulations. ACEMD is a production-class ...biomolecular dynamics (MD) engine supporting CHARMM and AMBER force fields. Designed specifically for GPUs it is able to achieve supercomputing scale performance of 40 ns/day for all-atom protein systems with over 23 000 atoms. We provide a validation and performance evaluation of the code and run a microsecond-long trajectory for an all-atom molecular system in explicit TIP3P water on a single workstation computer equipped with just 3 GPUs. We believe that microsecond time scale molecular dynamics on cost-effective hardware will have important methodological and scientific implications.
Electrical brain signals are often decomposed into frequency ranges that are implicated in different functions. Using subdural electrocorticography (ECoG, intracranial EEG) and functional magnetic ...resonance imaging (fMRI), we measured frequency spectra and BOLD responses in primary visual cortex (V1) and intraparietal sulcus (IPS). In V1 and IPS, 30–120Hz (gamma, broadband) oscillations allowed population receptive field (pRF) reconstruction comparable to fMRI estimates. Lower frequencies, however, responded very differently in V1 and IPS. In V1, broadband activity extends down to 3Hz. In the 4–7Hz (theta) and 18–30Hz (beta) ranges broadband activity increases power during stimulation within the pRF. However, V1 9–12Hz (alpha) frequency oscillations showed a different time course. The broadband power here is exceeded by a frequency-specific power increase during stimulation of the area outside the pRF. As such, V1 alpha oscillations reflected surround suppression of the pRF, much like negative fMRI responses. They were consequently highly localized, depending on stimulus and pRF position, and independent between nearby electrodes. In IPS, all 3–25Hz oscillations were strongest during baseline recording and correlated between nearby electrodes, consistent with large-scale disengagement. These findings demonstrate V1 alpha oscillations result from locally active functional processes and relate these alpha oscillations to negative fMRI signals. They highlight that similar oscillations in different areas reflect processes with different functional roles. However, both of these roles of alpha seem to reflect suppression of spiking activity.
► γ-Oscillations increase similarly during receptive field stimulation in V1 and IPS. ► V1 α-oscillations are local and reflect surround inhibition and negative fMRI signals. ► IPS slow oscillations, including α, reflect non-local large-scale disengagement. ► Similar oscillations in different visual areas have different roles.
The smooth particle mesh Ewald summation method is widely used to efficiently compute long-range electrostatic force terms in molecular dynamics simulations, and there has been considerable work in ...developing optimized implementations for a variety of parallel computer architectures. We describe an implementation for Nvidia graphical processing units (GPUs) which are general purpose computing devices with a high degree of intrinsic parallelism and arithmetic performance. We find that, for typical biomolecular simulations (e.g., DHFR, 26K atoms), a single GPU equipped workstation is able to provide sufficient performance to permit simulation rates of ≈50 ns/day when used in conjunction with the ACEMD molecular dynamics package and exhibits an accuracy comparable to that of a reference double-precision CPU implementation.
A systematic review of randomized controlled trials was conducted to evaluate the effectiveness of eHealth interventions for the prevention and treatment of overweight and obesity in adults. Eight ...databases were searched for studies published in English from 1995 to 17 September 2014. Eighty‐four studies were included, with 183 intervention arms, of which 76% (n = 139) included an eHealth component. Sixty‐one studies had the primary aim of weight loss, 10 weight loss maintenance, eight weight gain prevention, and five weight loss and maintenance. eHealth interventions were predominantly delivered using the Internet, but also email, text messages, monitoring devices, mobile applications, computer programs, podcasts and personal digital assistants. Forty percent (n = 55) of interventions used more than one type of technology, and 43.2% (n = 60) were delivered solely using eHealth technologies. Meta‐analyses demonstrated significantly greater weight loss (kg) in eHealth weight loss interventions compared with control (MD −2.70 −3.33,−2.08, P < 0.001) or minimal interventions (MD −1.40 −1.98,−0.82, P < 0.001), and in eHealth weight loss interventions with extra components or technologies (MD 1.46 0.80, 2.13, P < 0.001) compared with standard eHealth programmes. The findings support the use of eHealth interventions as a treatment option for obesity, but there is insufficient evidence for the effectiveness of eHealth interventions for weight loss maintenance or weight gain prevention.
Abstract Background Data on recent trends in mortality after hip fracture are scarce. Aims were therefore to examine secular trends in all-cause and cause-specific mortality post hip fracture and to ...compare this to the general population from 2000 to 2010. Methods Population-based cohort study within the United Kingdom Clinical Practice Research Datalink and linked to cause of death data for 57.7% of patients. Patients with a first hip fracture (n = 31,495) were matched to up to four controls by age, sex, index date, and practice. All subjects were followed for death, and lifestyle, disease and medication history adjusted hazard ratios (HRs) were calculated. Results One-year all-cause mortality after hip fracture declined from 2009 and was 14% lower after, compared with before 2009 (22.3% to 20.5%, adj. HR 0.86, 95% CI: 0.81–0.92). The decline was observed for males (≥ 75 years) and females (≥ 85 years). Significant contributors to the decline in mortality post hip fracture were respiratory infections in females as were malignant diseases in males. However, one-year all-cause mortality remained unaltered over the decade when compared to controls with a 3.5-fold and 2.4-fold increased risk in males and females respectively. No significant changes were observed in the relative risks for one-year cause-specific mortality for both genders. Conclusions One-year mortality after hip fracture has declined over the last decade in the UK. However, the difference in one-year mortality between hip fracture patients and the general population remained unaltered. These observations highlight the need for the continued implementation of evidence-based standards for good hip fracture care.
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