Superposed epoch analysis using time-normalization: A Python tool for statistical event analysis

A superposed epoch analysis (SEA) is a simple, yet powerful statistical analysis technique, used to identify patterns in the temporal evolution of observed quantities relative to defined epochs. In some cases, the event duration and time between epochs (epoch length) can be highly variable. If the measured response scales with the event duration or epoch length, then the underlying temporal patterns can be suppressed when analyzed in absolute time. In this article, we describe an adaptation of the traditional SEA, where we apply time-normalization to each event and present a Python package sea_norm which implements the time-normalized SEA. Rather than defining a singular epoch time, a start, epoch, and end time are defined for each event, separating each event into two intervals. For every event, the duration of both intervals is normalized to a common time axis, essentially stretching or compressing each interval, such that each respective epoch interval is the same length for all events. This technique has the advantage of identifying temporal patterns not observed in a traditional SEA. Given a time series, a list of event start, epoch, and end times, and specified binning dimensions the Python package sea_norm returns a time-normalized SEA analysis of the time-series. This technique is widely applicable across the Space Physics field, where events have defined start and end times, and where the response to those events may scale proportionally with event length. We provide examples demonstrating how the SEA code works with one-dimensional and two-dimensional time series, and how users can specify their own statistics to use in the superposed analysis (e.g., percentiles)

Dynamical simulations of an electronically induced solid-solid phase transformation in tungsten

The rearrangement of a material's electron density during laser irradiation leads to modified nonthermal forces on the atoms that may lead to coherent atomic motions and structural phase transformation on very short time scales. We present ab initio molecular dynamics simulations of a martensitic solid-solid phase transformation in tungsten under conditions of strong electronic excitation. The transformation is ultrafast, taking just over a picosecond, and follows the tetragonal Bain path. To examine whether a solid-solid bcc-fcc phase transformation could occur during laser irradiation, we use two-temperature molecular dynamics (2T-MD) simulations with a specially developed potential dependent on the electronic temperature. Our simulations show that the occurrence of the solid-solid phase transformation is in competition with ultrafast nonthermally assisted melting with the strength of the electron-phonon coupling determining the lifetime of the new solid phase. In tungsten the melting transition is predicted to occur too rapidly for the fcc phase to be detectable during laser irradiation

Leveraging Space-based Data from the Nearest Solar-type Star to Better Understand Stellar Activity Signatures in Radial Velocity Data

Stellar variability is a key obstacle in reaching the sensitivity required to recover Earth-like exoplanetary signals using the radial velocity (RV) detection method. To explore activity signatures in Sun-like stars, we present SolAster, a publicly distributed analysis pipeline10 that allows for comparison of space-based measurements with ground-based disk-integrated RVs. Using high-spatial-resolution Dopplergrams, magnetograms, and continuum filtergrams from the Helioseismic and Magnetic Imager aboard the Solar Dynamics Observatory (SDO), we estimate "Sun-as-a-star" disk-integrated RVs due to rotationally modulated flux imbalances and convective blueshift suppression, as well as other observables such as unsigned magnetic flux. Comparing these measurements with ground-based RVs from the NEID instrument, which observes the Sun daily using an automated solar telescope, we find a strong relationship between magnetic activity indicators and RV variation, supporting efforts to examine unsigned magnetic flux as a proxy for stellar activity in slowly rotating stars. Detrending against measured unsigned magnetic flux allows us to improve the NEID RV measurements by ∼20% (∼50 cm s−1 in a quadrature sum), yielding an rms scatter of ∼60 cm s−1 over five months. We also explore correlations between individual and averaged spectral line shapes in the NEID spectra and SDO-derived magnetic activity indicators, motivating future studies of these observables. Finally, applying SolAster to archival planetary transits of Venus and Mercury, we demonstrate the ability to recover small amplitude (<50 cm s−1) RV variations in the SDO data by directly measuring the Rossiter–McLaughlin signals

Leveraging Space-based Data from the Nearest Solar-type Star to Better Understand Stellar Activity Signatures in Radial Velocity Data

Stellar variability is a key obstacle in reaching the sensitivity required to recover Earth-like exoplanetary signals using the radial velocity (RV) detection method. To explore activity signatures in Sun-like stars, we present SolAster, a publicly distributed analysis pipeline10 that allows for comparison of space-based measurements with ground-based disk-integrated RVs. Using high-spatial-resolution Dopplergrams, magnetograms, and continuum filtergrams from the Helioseismic and Magnetic Imager aboard the Solar Dynamics Observatory (SDO), we estimate "Sun-as-a-star" disk-integrated RVs due to rotationally modulated flux imbalances and convective blueshift suppression, as well as other observables such as unsigned magnetic flux. Comparing these measurements with ground-based RVs from the NEID instrument, which observes the Sun daily using an automated solar telescope, we find a strong relationship between magnetic activity indicators and RV variation, supporting efforts to examine unsigned magnetic flux as a proxy for stellar activity in slowly rotating stars. Detrending against measured unsigned magnetic flux allows us to improve the NEID RV measurements by ∼20% (∼50 cm s−1 in a quadrature sum), yielding an rms scatter of ∼60 cm s−1 over five months. We also explore correlations between individual and averaged spectral line shapes in the NEID spectra and SDO-derived magnetic activity indicators, motivating future studies of these observables. Finally, applying SolAster to archival planetary transits of Venus and Mercury, we demonstrate the ability to recover small amplitude (<50 cm s−1) RV variations in the SDO data by directly measuring the Rossiter–McLaughlin signals

Patient enablement requires physician empathy: a cross-sectional study of general practice consultations in areas of high and low socioeconomic deprivation in Scotland

<b>Background</b> Patient 'enablement' is a term closely aligned with 'empowerment' and its measurement in a general practice consultation has been operationalised in the widely used patient enablement instrument (PEI), a patient-rated measure of consultation outcome. However, there is limited knowledge regarding the factors that influence enablement, particularly the effect of socio-economic deprivation. The aim of the study is to assess the factors influencing patient enablement in GP consultations in areas of high and low deprivation.<p></p> <b>Methods</b> A questionnaire study was carried out on 3,044 patients attending 26 GPs (16 in areas of high socio-economic deprivation and 10 in low deprivation areas, in the west of Scotland). Patient expectation (confidence that the doctor would be able to help) was recorded prior to the consultation. PEI, GP empathy (measured by the CARE Measure), and a range of other measures and variables were recorded after the consultation. Data analysis employed multi-level modelling and multivariate analyses with the PEI as the dependant variable.<p></p> <b>Results</b> Although numerous variables showed a univariate association with patient enablement, only four factors were independently predictive after multilevel multivariate analysis; patients with multimorbidity of 3 or more long-term conditions (reflecting poor chronic general health), and those consulting about a long-standing problem had reduced enablement scores in both affluent and deprived areas. In deprived areas, emotional distress (GHQ-caseness) had an additional negative effect on enablement. Perceived GP empathy had a positive effect on enablement in both affluent and deprived areas. Maximal patient enablement was never found with low empathy.<p></p> <b>Conclusions</b> Although other factors influence patient enablement, the patients' perceptions of the doctors' empathy is of key importance in patient enablement in general practice consultations in both high and low deprivation settings

Fermions scattering in a three dimensional extreme black hole background

The absorption cross section for scattering of fermions off an extreme BTZ black hole is calculated. It is shown that, as in the case of scalar particles, an extreme BTZ black hole exhibits a vanishing absorption cross section, which is consistent with the vanishing entropy of such object. Additionally, we give a general argument to prove that the particle flux near the horizon is zero. Finally we show that the {\it reciprocal space} introduced previously in \cite{gm} gives rise to the same result and, therefore, it could be considered as the space where the scattering process takes place in an AdS spacetime.Comment: 15 pages, RevTex4. Revised version. To be published in Class. Quantum. Gra

A natural polymorphism of Mycobacterium tuberculosis in the esxH gene disrupts immunodomination by the TB10.4-specific CD8 T cell response

CD8 T cells provide limited protection against Mycobacterium tuberculosis (Mtb) infection in the mouse model. As Mtb causes chronic infection in mice and humans, we hypothesize that Mtb impairs T cell responses as an immune evasion strategy. TB10.4 is an immunodominant antigen in people, nonhuman primates, and mice, which is encoded by the esxH gene. In C57BL/6 mice, 30-50% of pulmonary CD8 T cells recognize the TB10.44-11 epitope. However, TB10.4-specific CD8 T cells fail to recognize Mtb-infected macrophages. We speculate that Mtb elicits immunodominant CD8 T cell responses to antigens that are inefficiently presented by infected cells, thereby focusing CD8 T cells on nonprotective antigens. Here, we leverage naturally occurring polymorphisms in esxH, which frequently occur in lineage 1 strains, to test this decoy hypothesis . Using the clinical isolate 667, which contains an EsxHA10T polymorphism, we observe a drastic change in the hierarchy of CD8 T cells. Using isogenic Erd.EsxHA10T and Erd.EsxHWT strains, we prove that this polymorphism alters the hierarchy of immunodominant CD8 T cell responses. Our data are best explained by immunodomination, a mechanism by which competition for APC leads to dominant responses suppressing subdominant responses. These results were surprising as the variant epitope can bind to H2-Kb and is recognized by TB10.4-specific CD8 T cells. The dramatic change in TB10.4-specific CD8 responses resulted from increased proteolytic degradation of A10T variant, which destroyed the TB10.44-11epitope. Importantly, this polymorphism affected T cell priming and recognition of infected cells. These data support a model in which nonprotective CD8 T cells become immunodominant and suppress subdominant responses. Thus, polymorphisms between clinical Mtb strains, and BCG or H37Rv sequence-based vaccines could lead to a mismatch between T cells that are primed by vaccines and the epitopes presented by infected cells. Reprograming host immune responses should be considered in the future design of vaccines

‘Like the stranger at a funeral who cries more than the bereaved’: ethical dilemmas in ethnographic research with children

This article contributes to debates on the practicality and utility of prior ethical review in ethnography and qualitative research using an ethnography of children’s involvement in artisanal gold mining work in Ghana as a case study. Reflecting on dilemmas and obstacles encountered in attempts to employ prescribed institutional ethical guidance modelled for childhood research in the UK during the fieldwork, the discussion brings to attention some of the problems that can arise when ethical guidance is not anchored in the lived realities or value systems of the setting in which fieldwork is conducted. The article seeks to rejuvenate calls for more flexible and socio-culturally responsive ethical review and practice as an alternative to the prescriptive ethical regimes

Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR

Engineering protein processing of the mammary gland to produce abundant hemophilia B therapy in milk

Both the low animal cell density of bioreactors and their ability to post-translationally process recombinant factor IX (rFIX) limit hemophilia B therapy to transgenic pigs to make rFIX in milk at about 3,000-fold higher output than provided by industrial bioreactors. However, this resulted in incomplete γ-carboxylation and propeptide cleavage where both processes are transmembrane mediated. We then bioengineered the co-expression of truncated, soluble human furin (rFurin) with pro-rFIX at a favorable enzyme to substrate ratio. This resulted in the complete conversion of pro-rFIX to rFIX while yielding a normal lactation. Importantly, these high levels of propeptide processing by soluble rFurin did not preempt γ-carboxylation in the ER and therefore was compartmentalized to the Trans-Golgi Network (TGN) and also to milk. The Golgi specific engineering demonstrated here segues the ER targeted enhancement of γ-carboxylation needed to biomanufacture coagulation proteins like rFIX using transgenic livestock