Towards precision particle background estimation for future X-ray missions: correlated variability between Chandra ACIS and AMS

A science goal of many future X-ray observatories is mapping the cosmic web through deep exposures of faint diffuse sources. Such observations require low background and the best possible knowledge of the remaining unrejected background. The dominant contribution to the background above 1-2 keV is from Galactic Cosmic Ray protons. Their flux and spectrum are modulated by the solar cycle but also by solar activity on shorter timescales. Understanding this variability may prove crucial to reducing background uncertainty for ESA's Athena X-ray Observatory and other missions with large collecting area. We examine of the variability of the particle background as measured by ACIS on the Chandra X-ray Observatory and compare that variability to that measured by the Alpha Magnetic Spectrometer (AMS), a precision particle detector on the ISS. We show that cosmic ray proton variability measured by AMS is well matched to the ACIS background and can be used to estimate proton energies responsible for the background. We discuss how this can inform future missions.Comment: 11 pages, 8 figures, submitted to Proceedings of SPIE Astronomical Telescopes + Instrumentation 202

G2Cdb: the Genes to Cognition database

Neuroscience databases linking genes, proteins, (patho)physiology, anatomy and behaviour across species will be valuable in a broad range of studies of the nervous system. G2Cdb is such a neuroscience database aiming to present a global view of the role of synapse proteins in physiology and disease. G2Cdb warehouses sets of genes and proteins experimentally elucidated by proteomic mass spectroscopy of signalling complexes and proteins biochemically isolated from mammalian synapse preparations, giving an experimentally validated definition of the constituents of the mammalian synapse. Using automated text-mining and expert (human) curation we have systematically extracted information from published neurobiological studies in the fields of synaptic signalling electrophysiology and behaviour in knockout and other transgenic mice. We have also surveyed the human genetics literature for associations to disease caused by mutations in synaptic genes. The synapse proteome datasets that G2Cdb provides offer a basis for future work in synapse biology and provide useful information on brain diseases. They have been integrated in a such way that investigators can rapidly query whether a gene or protein is found in brain-signalling complex(es), has a phenotype in rodent models or whether mutations are associated with a human disease. G2Cdb can be freely accessed at http://www.genes2cognition.org

A randomised feasibility study to investigate the impact of education and the addition of prompts on the sedentary behaviour of office workers

Abstract Background Office workers have been identified as being at risk of accumulating high amounts of sedentary time in prolonged events during work hours, which has been associated with increased risk of a number of long-term health conditions. There is some evidence that providing advice to stand at regular intervals during the working day, and using computer-based prompts, can reduce sedentary behaviour in office workers. However, evidence of effectiveness, feasibility and acceptability for these types of intervention is currently limited. Methods A 2-arm, parallel group, cluster-randomised feasibility trial to assess the acceptability of prompts to break up sedentary behaviour was conducted with office workers in a commercial bank (n = 21). Participants were assigned to an education only group (EG) or prompt and education group (PG). Both groups received education on reducing and breaking up sitting at work, and the PG also received hourly prompts, delivered by Microsoft Outlook over 10 weeks, reminding them to stand. Objective measurements of sedentary behaviour were made using activPAL monitors worn at three time points: baseline, in the last 2 weeks of the intervention period and 12 weeks after the intervention. Focus groups were conducted to explore the acceptability of the intervention and the motivations and barriers to changing sedentary behaviour. Results Randomly generated, customised prompts, delivered by Microsoft Outlook, with messages about breaking up sitting, proved to be a feasible and acceptable way of delivering prompts to office workers. Participants in both groups reduced their sitting, but changes were not maintained at follow-up. The education session seemed to increase outcome expectations of the benefits of changing sedentary behaviour and promote self-regulation of behaviour in some participants. However, low self-efficacy and a desire to conform to cultural norms were barriers to changing behaviour. Conclusions Prompts delivered by Microsoft Outlook were a feasible, low-cost way of prompting office workers to break up their sedentary behaviour, although further research is needed to determine whether this has an additional impact on sedentary behaviour, to education alone. The role of cultural norms, and promoting self-efficacy, should be considered in the design of future interventions. Trial registration This study was registered retrospectively as a clinical trial on ClinicalTrials.gov (ID no. NCT02609282 ) on 23 March 2015

The Distinct Conformational Dynamics of K-Ras and H-Ras A59G

Ras proteins regulate signaling cascades crucial for cell proliferation and differentiation by switching between GTP- and GDP-bound conformations. Distinct Ras isoforms have unique physiological functions with individual isoforms associated with different cancers and developmental diseases. Given the small structural differences among isoforms and mutants, it is currently unclear how these functional differences and aberrant properties arise. Here we investigate whether the subtle differences among isoforms and mutants are associated with detectable dynamical differences. Extensive molecular dynamics simulations reveal that wild-type K-Ras and mutant H-Ras A59G are intrinsically more dynamic than wild-type H-Ras. The crucial switch 1 and switch 2 regions along with loop 3, helix 3, and loop 7 contribute to this enhanced flexibility. Removing the gamma-phosphate of the bound GTP from the structure of A59G led to a spontaneous GTP-to-GDP conformational transition in a 20-ns unbiased simulation. The switch 1 and 2 regions exhibit enhanced flexibility and correlated motion when compared to non-transitioning wild-type H-Ras over a similar timeframe. Correlated motions between loop 3 and helix 5 of wild-type H-Ras are absent in the mutant A59G reflecting the enhanced dynamics of the loop 3 region. Taken together with earlier findings, these results suggest the existence of a lower energetic barrier between GTP and GDP states of the mutant. Molecular dynamics simulations combined with principal component analysis of available Ras crystallographic structures can be used to discriminate ligand- and sequence-based dynamic perturbations with potential functional implications. Furthermore, the identification of specific conformations associated with distinct Ras isoforms and mutants provides useful information for efforts that attempt to selectively interfere with the aberrant functions of these species

Implementation of mandatory opioid prescribing limits in North Carolina: healthcare administrator and prescriber perspectives

Background: Recent increases in state laws to reduce opioid prescribing have demonstrated a need to understand how they are interpreted and implemented in healthcare systems. The purpose of this study was to explore the systems, strategies, and resources that hospital administrators and prescribers used to implement the 2017 North Carolina Strengthen Opioid Prevention (STOP) Act opioid prescribing limits, which limited initial prescriptions to a five (for acute) or seven (for post-surgical) days’ supply. Methods: We interviewed 14 hospital administrators and 38 prescribers with degrees in medicine, nursing, pharmacy, business administration and public health working across North Carolina. Interview guides, informed by the Consolidated Framework for Implementation Research, explored barriers and facilitators to implementation. Interview topics included communication, resources, and hospital system support. Interviews were recorded and transcribed, then analyzed using flexible coding, integrating inductive and deductive coding, to inform analytic code development and identify themes. Results: We identified three main themes around implementation of STOP act mandated prescribing limits: organizational communication, prescriber education, and changes in the electronic medical record (EMR) systems. Administrators reflected on implementation in the context of raising awareness and providing reminders to facilitate changes in prescriber behavior, operationalized through email and in-person communications as well as dedicated resources to EMR changes. Prescribers noted administrative communications about prescribing limits often focused on legality, suggesting a directive of the organization’s policy rather than a passive reminder. Prescribers expressed a desire for more spaces to have their questions answered and resources for patient communications. While hospital administrators viewed compliance with the law as a priority, prescribers reflected on concerns for adequately managing their patients’ pain and limited time for clinical care. Conclusions: Hospital administrators and prescribers approached implementation of the STOP act prescribing limits with different mindsets. While administrators were focused on policy compliance, prescribers were focused on their patients’ needs. Strategies to implement the mandate then had to balance patient needs with policy compliance. As states continue to legislate to prevent opioid overdose deaths, understanding how laws are implemented by healthcare systems and prescribers will improve their effectiveness through tailoring and maximizing available resources

Patient and general practitioner attitudes to taking medication to prevent cardiovascular disease after receiving detailed information on risks and benefits of treatment: a qualitative study

Abstract Background There are now effective drugs to prevent cardiovascular disease and guidelines recommend their use. Patients do not always choose to accept preventive medication at levels of risk reduction recommended in guidelines. The purpose of the study was to identify and explore the attitudes of patients and general practitioners towards preventative medication for cardiovascular disease (CVD) after they have received information about it; to identify implications for practice and prescribing. Methods Qualitative interviews with GPs and patients following presentation of in depth information about CVD risks and the absolute effects of medication. Setting: GP practices in Birmingham, United Kingdom. Results In both populations: wide variation on attitudes to preventative medication; concerns about unnecessary drug taking & side effects; preferring to consider lifestyle changes first. In patient population: whatever their attitudes to medication were, the vast majority explained that they would ultimately do what their GP recommended; there was some misunderstanding of the distinction between curative and preventative medication. A common theme was the degree of trust in their doctors' judgement and recommendations, which contrasted with scepticism of the role of pharmaceutical companies and academics. Scepticism in guidelines was also common among doctors although many nevertheless recommended treatment for their patients Conclusions A guideline approach to prescribing preventative medication could be against the interests and preferences of the patient. GPs must take extra care to explain what preventative medication is and why it is recommended, attempt to discern preferences and make recommendations balancing these potentially conflicting concerns.</p

Adults' past-day recall of sedentary time: reliability, validity and responsiveness

Purpose: Past-day recall rather than recall of past week or a usual/typical day may improve the validity of self-reported sedentary time measures. This study examined the test-retest reliability, criterion validity, and responsiveness of the seven-item questionnaire, Past-day Adults' Sedentary Time (PAST). Methods: Participants (breast cancer survivors, n = 90, age = 33-75 yr, body mass index = 25-40 kg.m(-2)) in a 6-month randomized controlled trial of a lifestyle-based weight loss intervention completed the interviewer-administered PAST questionnaire about time spent sitting/lying on the previous day for work, transport, television viewing, nonwork computer use, reading, hobbies, and other purposes (summed for total sedentary time). The instrument was administered at baseline, 7 d later for test-retest reliability (n = 86), and at follow-up. ActivPAL3-assessed sit/lie time in bouts of >= 5 min during waking hours on the recall day was used as the validity criterion measure at both baseline (n = 72) and follow-up (n = 68). Analyses included intraclass correlation coefficients, Pearson's correlations (r), and Bland-Altman plots and responsiveness index. Results: The PAST had fair to good test-retest reliability (intraclass correlation coefficient = 0.50, 95% confidence interval [CI] = 0.32-0.64). At baseline, the correlation between PAST and activPAL sit/lie time was r = 0.57 (95% CI = 0.39-0.71). The mean difference between PAST at baseline and retest was -25 min (5.2%), 95% limits of agreement = -5.9 to 5.0 h, and the activPAL sit/lie time was -9 min (1.8%), 95% limits of agreement = -4.9 to 4.6 h. The PAST showed small but significant responsiveness (-0.44, 95% CI = -0.92 to -0.04); responsiveness of activPAL sit/lie time was not significant. Conclusion: The PAST questionnaire provided an easy-to-administer measure of sedentary time in this sample. Validity and reliability findings compare favorably with other sedentary time questionnaires. Past-day recall of sedentary time shows promise for use in future health behavior, epidemiological, and population surveillance studies

The AEPEX Mission: Imaging Energetic Particle Precipitation in the Atmosphere through its Bremsstrahlung X-ray Signatures

The Atmospheric Effects of Precipitation through Energetic X-rays (AEPEX) mission is a 6U CubeSat that will monitor energetic electron precipitation from the radiation belts into the upper atmosphere. The primary instrument will image energetic (50&ndash;300 keV) X-rays produced in the atmosphere by bremsstrahlung, providing a near-direct signature of electron precipitation. An energetic electron detector will measure the precipitating electron spectrum, while the X-ray observations will be used to determine the absolute flux. X-ray images will be produced with 10-s time resolution and 50&ndash;100 km spatial resolution. The 6U spacecraft uses flight heritage spacecraft bus subsystems, including the attitude determination and control, electrical power, and command &amp; data handling systems. AEPEX is designed to be operated from low-Earth orbit at ~500 km altitude with a high inclination in order to cover the outer radiation belt. AEPEX will be the first spacecraft mission to measure X-rays in the 50&ndash;300 keV energy range emitted by Earth&rsquo;s atmosphere in response to radiation belt precipitation, and the first to image that precipitation from above.</p