Forward modeling the orbits of companions to pulsating stars from their light travel time variations

Mutual gravitation between a pulsating star and an orbital companion leads to a time-dependent variation in path length for starlight traveling to Earth. These variations can be used for coherently pulsating stars, such as the {\delta} Scuti variables, to constrain the masses and orbits of their companions. Observing these variations for {\delta} Scuti stars has previously relied on subdividing the light curve and measuring the average pulsation phase in equally sized subdivisions, which leads to under-sampling near periapsis. We introduce a new approach that simultaneously forward-models each sample in the light curve and show that this method improves upon current sensitivity limits - especially in the case of highly eccentric and short-period binaries. We find that this approach is sensitive enough to observe Jupiter mass planets around {\delta} Scuti stars under ideal conditions, and use gravity-mode pulsations in the subdwarf B star KIC 7668647 to detect its companion without radial velocity data. We further provide robust detection limits as a function of the SNR of the pulsation mode and determine that the minimum detectable light travel time amplitude for a typical Kepler {\delta} Scuti is around 2 s. This new method significantly enhances the application of light travel time variations to detecting short period binaries with pulsating components, and pulsating A-type exoplanet host stars, especially as a tool for eliminating false positives.Comment: 14 pages, accepted for publication in A

Hydrophobic residues at position 10 of α-conotoxin PnIA influence subtype selectivity between α7 and α3β2 neuronal nicotinic acetylcholine receptors

Neuronal nicotinic acetylcholine receptors (nAChRs) are a diverse class of ligand-gated ion channels involved in neurological conditions such as neuropathic pain and Alzheimer's disease. α-Conotoxin [A10L]PnIA is a potent and selective antagonist of the mammalian α7 nAChR with a key binding interaction at position 10. We now describe a molecular analysis of the receptor-ligand interactions that determine the role of position 10 in determining potency and selectivity for the α7 and α3β2 nAChR subtypes. Using electrophysiological and radioligand binding methods on a suite of [A10L]PnIA analogs we observed that hydrophobic residues in position 10 maintained potency at both subtypes whereas charged or polar residues abolished α7 binding. Molecular docking revealed dominant hydrophobic interactions with several α7 and α3β2 receptor residues via a hydrophobic funnel. Incorporation of norleucine (Nle) caused the largest (8-fold) increase in affinity for the α7 subtype (Ki = 44 nM) though selectivity reverted to α3β2 (IC50 = 0.7 nM). It appears that the placement of a single methyl group determines selectivity between α7 and α3β2 nAChRs via different molecular determinants

Analysis of ferrite formed in 321 grade austenitic stainless steel

A significant fraction of ferrite has been identified in a 321 grade austenitic stainless steel in the solution heat treated condition. The microstructures were analysed using electron backscatter diffraction, energy dispersive X-ray spectroscopy and X-ray diffraction (XRD) and the stability of the ferrite investigated using heat treatments in a tube furnace, dilatometry and high temperature XRD. The ferrite dissolved ,800uC, then formed again on cooling at temperatures under 200uC. Thermodynamic predictions showed a significant ferrite content at room temperature under equilibrium conditions, and the DeLong diagrams predict an austenitezmartensite microstructure in the cast condition. Sensitivity analysis on the DeLong diagram has shown that the nitrogen content had a large effect on the austenite stability. The instability of the austenite and the subsequent transformation to ferrite on cooling can be attributed to low nitrogen content measured in the as received material. It was found that thermal aging of the material caused further transformation of austenite to ferrite as well as the formation of sigma phase that appears higher in nitrogen than the matrix phases. The diffusion of nitrogen into sigma phase may cause instability of the austenite, which could cause further transformation of austenite to ferrite on cooling from the aging temperature. The transformation of austenite to ferrite is known to be accompanied by an increase in volume, which may be of relevance to components made with tight dimensional tolerances

Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results showed that resveratrol and acetyl-resveratrol reduced cell growth in the SKOV-3 and OVCAR-8 in a dose-dependant manner. The growth reduction was mediated by the induction of apoptosis via the cleavage of poly(ADP-ribose) polymerase (PARP-1). At lower concentrations, 5 and 10 µM, resveratrol, acetyl-resveratrol, and polydatin were less effective than higher concentrations, 50 and 100 µM. In SKOV-3 line, at higher concentrations, resveratrol and polydatin significantly reduced the phosphorylation of Her-2 and EGFR and the expression of Erk. Acetyl-resveratrol, on the other hand, did not change the activation of Her-2 and EGFR. Resveratrol, acetyl-resveratrol, and polydatin suppressed the secretion of VEGF in a dose-dependant fashion. In the OVCAR-8 cell line, resveratrol and acetyl-resveratrol at 5 and 10 µM increased the activation of Erk. Above these concentrations they decreased activation. Polydatin did not produce this effect. This study demonstrates that resveratrol and its derivatives may inhibit growth of 3D cell aggregates of ovarian cancer cell lines via different signalling molecules. Resveratrol and its derivatives, therefore, warrant further in vivo evaluation to assess their potential clinical utility

Super Residual Circulation : A New Perspective on Ocean Vertical Heat Transport

Ocean circulation and mixing regulate Earth's climate by moving heat vertically within the ocean. We present a new formalism to diagnose the role of ocean circulation and diabatic processes in setting vertical heat transport in ocean models. In this formalism we use temperature tendencies, rather than explicit vertical velocities, to diagnose circulation. Using quasi-steady-state simulations from the Australian Community Climate and Earth-System Simulator Ocean Model (ACCESS-OM2), we diagnose a diathermal overturning circulation in temperature-depth space. Furthermore, projection of tendencies due to diabatic processes onto this coordinate permits us to represent these as apparent overturning circulations. Our framework permits us to extend the concept of "Super Residual Transport,'' which combines mean and eddy advection terms with subgridscale isopycnal mixing due to mesoscale eddies but excludes small-scale threedimensional turbulent mixing effect, to construct a new overturning circulation-the "Super Residual Circulation'' (SRC). We find that in the coarse-resolution version of ACCESS-OM2 (nominally 1 degrees horizontal resolution) the SRC is dominated by an similar to 11-Sv (1 Sv [10(6) m(3) s(-1)) circulation that transports heat upward. The SRC's upward heat transport is;2 times as large in a finer-horizontal-resolution (0.1 degrees) version of ACCESS, suggesting that a differing balance of super-residual and parameterized small-scale processes may emerge as eddies are resolved. Our analysis adds new insight into superresidual processes, because the SRC elucidates the pathways in temperature and depth space along which water mass transformation occurs.Peer reviewe

The lay health worker-patient relationship in promoting pulmonary rehabilitation (PR) in COPD: What makes it work?

Lay health workers (LHWs) can improve access to services and adherence to treatment, as well as promoting self-care and prevention. Their effect in promoting uptake and adherence in pulmonary rehabilitation (PR) for chronic obstructive pulmonary disease (COPD) has not been tested. PR is the most effective treatment for the symptoms and disability of COPD, but this effectiveness is undermined by poor rates of completion. Trained LHWs with COPD, who also have first-hand experience of PR, are well placed to help overcome the documented barriers to its completion. The relationship between LHWs and patients may be one of the keys to their effectiveness but it has been little explored. Semi-structured qualitative interviews were used with the aim of examining the LHW-patient partnership in a feasibility study of trained PR-experienced LHWs used to support COPD patients referred to PR. Twelve volunteers with COPD who completed LHW training supported 66 patients referred for PR. All 12 of these LHWs gave end-of-study interviews, 21 COPD patients supported by LHWs were also interviewed. Patients reported that the LHWs were keen to share their experiences of PR, and that this had a positive impact. The enthusiasm of the LHWs for PR was striking. The common bond between LHWs and patients of having COPD together with the LHWs positive, first-hand experience of PR were dominant and recurring themes in their relationship.This article presents independent research funded by the NIHR under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG0214-30052). SL receives additional funding from the South African Medical Research Council. SJCT was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Bart’s Health NHS Trust

Effectiveness of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual non-inferiority trial

Objectives: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD). Design: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard). Setting: Internet-based application. Participants: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care. Interventions: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes. Main outcome measures: Primary outcome- correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions. Results: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists. Conclusions: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals

Understanding patient profiles and characteristics of current chiropractic practice: a cross-sectional Ontario Chiropractic Observation and Analysis STudy (O-COAST)

Objectives There is no current detailed profile of people seeking chiropractic care in Canada. We describe the profiles of chiropractors’ practice and the reasons, nature of the care provided to their patients and extent of interprofessional collaborations in Ontario, Canada. Design Cross-sectional observational study. Setting Primary care setting in Ontario, Canada. Participants We randomly recruited chiropractors from a list of registered chiropractors (n=3978) in active practice in 2015. Of the 135 randomly selected chiropractors, 120 were eligible, 43 participated and 42 completed the study.Outcome measures Each chiropractor recorded information for up to 100 consecutive patient encounters, documenting patient health profiles, reasons for encounter, diagnoses and care provided. Descriptive statistics summarised chiropractor, patient and encounter characteristics, with analyses accounting for clustering and design effects. Results Chiropractors provided data on 3523 chiropractor-patient encounters. More than 65% of participating chiropractors were male, mean age 44 years and had practised on average 15 years. The typical patient was female (59% of encounters), between 45 and 64 years (43%) and retired (21%) or employed in business and administration (13%). Most (39.4%) referrals were from other patients, with 6.8% from physicians. Approximately 68% of patients paid out of pocket or claimed extended health insurance for care. Most common diagnoses were back (49%, 95% CI 44 to 56) and neck (15%, 95% CI 13 to 18) problems, with few encounters related to maintenance/preventive care (0.86%, 95% CI 0.2 to 3.9) and non-musculoskeletal problems (1.3%, 95% CI 0.7 to 2.3). The most common treatments included spinal manipulation (72%), soft tissue therapy (70%) and mobilisation (35%). Conclusions This is the most comprehensive profile to date of chiropractic practice in Canada. People who present to Ontario chiropractors are mostly adults with a musculoskeletal condition. Our results can be used by stakeholders to make informed decisions about workforce development, education and healthcare policy related to chiropractic care

The Effectiveness, cost-effectiveness and acceptability of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES): a virtual randomised balanced incomplete block trial

Background Patients with neovascular age-related macular degeneration (nAMD) usually attend regular reviews, even when the disease is quiescent. Reviews are burdensome to health services, patients and carers. Objectives To compare the proportion of correct lesion classifications made by community-based optometrists and ophthalmologists from vignettes of patients; to estimate the cost-effectiveness of community follow-up by optometrists compared with follow-up by ophthalmologists in the Hospital Eye Service (HES); to ascertain views of patients, their representatives, optometrists, ophthalmologists and clinical commissioners on the proposed shared care model. Design Community-based optometrists and ophthalmologists in the HES classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomography images. Participants’ classifications were validated against experts’ classifications (reference standard). Setting Internet-based application. Participants Ophthalmologists had to have≥3 years post-registration experience in ophthalmology, have passed part 1 of the Royal College of Ophthalmologists, Diploma in Ophthalmology or equivalent examination, and have experience in the age-related macular degeneration service. Optometrists had to be fully qualified, be registered with the General Optical Council for≥3 years and not be participating in nAMD shared care. Interventions The trial sought to emulate a conventional trial in comparing optometrists’ and ophthalmologists’ decision-making, but vignettes, not patients, were assessed; therefore, there were no interventions. Participants received training prior to assessing vignettes Main Outcome Measures Primary outcome–correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes–frequencies of potentially sight-threatening errors, participants’ judgements about specific lesion components, participant-rated confidence in their decisions and cost-effectiveness of follow-up by community-based optometrists compared with HES ophthalmologists. Results In total, 155 participants registered for the trial; 96 (48 in each professional group) completed training and main assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702 out of 2016 (84.4%) and 1722 out of 2016 (85.4%) correct classifications, respectively [odds ratio (OR) 0.91, 95% confidence interval (CI) 0.66 to 1.25; p=0.543]. Optometrists’ decisionmaking was non-inferior to ophthalmologists’ with respect to the pre-specified limit of 10% absolute difference (0.298 on the odds scale). Frequencies of sight-threatening errors were similar for optometrists and ophthalmologists [57/994 (5.7%) vs. 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57;p=0.789]. Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their lesion classifications than optometrists. The mean care-pathway cost for assessment was very similar by group, namely £397.33 for ophthalmologists and £410.78 for optometrists. The optometrist-led monitoring reviews were slightly more costly and less effective than ophthalmologist-led reviews, although the differences were extremely small. There was consensus that optometrist-led monitoring has the potential to reduce clinical workload and be more patient-centred. However, potential barriers are ophthalmologists’ perceptions of optometrists’ competence, the need for clinical training, the ability of the professions to work collaboratively and the financial feasibility of shared care for Clinical Commissioning Groups Conclusions The ability of optometrists to make nAMD retreatment decisions from vignettes is non-inferior to that of ophthalmologists. Various barriers to implementing shared cared for nAMD were identified. Future Work Recommendations The Effectiveness, cost-effectiveness and acceptability of Community versus Hospital Eye Service follow-up for patients with neovascular age-related macular degeneration with quiescent disease (ECHoES) study web application was robust and could be used for future training or research. The benefit of reducing HES workload was not considered in the economic evaluation. A framework of programme budgeting and marginal analysis could explicitly explore the resource implications of shifting resources within a given health service area, as the benefit of reducing HES workload was not considered in the economic evaluation. Future qualitative research could investigate professional differences of opinion that were identified in multidisciplinary focus groups.</p

Late-epoch optical and near-infrared observations of the GRB000911 afterglow and its host galaxy

We present the results of an optical and near-infrared (NIR) monitoring campaign of the counterpart of Gamma-Ray Burst (GRB) 000911, located at redshift z=1.06, from 5 days to more than 13 months after explosion. Our extensive dataset is a factor of 2 larger and spans a time interval about 4 times longer than the ones considered previously for this GRB afterglow; this allows a more thorough analysis of its light curve and of the GRB host galaxy properties. The afterglow light curves show a single power-law temporal decline, modified at late times by light from a host galaxy with moderate intrinsic extinction, and possibly by an emerging supernova (SN). The afterglow evolution is interpreted within the classical "fireball" scenario as a weakly collimated adiabatic shock propagating in the interstellar medium. The presence of a SN light curve superimposed on the non-thermal afterglow emission is investigated: while in the optical bands no significant contribution to the total light is found from a SN, the NIR J-band data show an excess which is consistent with a SN as bright as the known hypernova SN1998bw. If the SN interpretation is true, this would be the farthest GRB-associated SN, as well as the farthest core-collapse SN, discovered to date. However, other possible explanations of this NIR excess are also investigated. Finally, we studied the photometric properties of the host, and found that it is likely to be a slightly reddened, subluminous, extreme starburst compact galaxy, with luminosity about 0.1 L*, an age of about 0.5 Gyr and a specific Star Formation Rate (SFR) of approximately 30 Msol yr-1 (L/L*)-1. This is the highest specific SFR value for a GRB host inferred from optical/NIR data.Comment: 13 pages, 6 figures, 3 tables. Accepted for publication in A&A, main journa