OSCAR (Osteopathic Single CAse Research) – assessing the effect of standard and biopsychosocial osteopathic management for patients with non-specific low back pain: protocol for a Single Case Experimental Design (SCED)

Background Osteopathy has been shown to be effective in the management of chronic low back pain (LBP). Guidelines recommend biopsychosocial care for chronic, complex musculoskeletal conditions, including non-specific LBP. Objectives This study has four aims: 1/to assess how patients with LBP improve after osteopathic treatment, both before and after an osteopath has completed a Biopsychosocial Pain Management course; 2/to assess if it is feasible and acceptable for osteopaths to receive weekly SCED data and use it to guide patient management; 3/to assess if it is acceptable for patients to submit daily data and discuss weekly summary with their osteopaths; and 4/to test feasibility for researchers in collecting, managing and storing large quantities of individual patient data. Methods A multiple baseline single case experimental design trial with up to 10 UK osteopaths with more than 15 years in practice and 60 patients will assess how change occurs as a result of osteopathic treatment for patients with non-specific LBP of more than 12 weeks’ duration. Statistical analysis will assess the degree and rate of change between baseline, intervention and follow-up periods, and whether differences in effect are observed after the osteopaths have completed the biopsychosocial patient management training course. Primary outcomes will be the Numeric Pain Rating and Patient Specific Function Scales, measured daily at baseline and for 6 weeks during the intervention stage, and weekly or fortnightly during a 12-week follow-up period. Ethics This research was approved by the XXX Research Ethics Committee

NuSTAR Observations of the Magnetar 1E 2259+586

We report on new broad band spectral and temporal observations of the magnetar 1E 2259+586, which is located in the supernova remnant CTB 109. Our data were obtained simultaneously with the Nuclear Spectroscopic Telescope Array (NuSTAR) and Swift, and cover the energy range from 0.5-79 keV. We present pulse profiles in various energy bands and compare them to previous RXTE results. The NuSTAR data show pulsations above 20 keV for the first time and we report evidence that one of the pulses in the double-peaked pulse profile shifts position with energy. The pulsed fraction of the magnetar is shown to increase strongly with energy. Our spectral analysis reveals that the soft X-ray spectrum is well characterized by an absorbed double-blackbody or blackbody plus power-law model in agreement with previous reports. Our new hard X-ray data, however, suggests that an additional component, such as a power-law, is needed to describe the NuSTAR and Swift spectrum. We also fit the data with the recently developed coronal outflow model by Beloborodov for hard X-ray emission from magnetars. The outflow from a ring on the magnetar surface is statistically preferred over outflow from a polar cap.Comment: 37 pages, 9 figures, corresponding author, [email protected]

The First Focused Hard X-ray Images of the Sun with NuSTAR

We present results from the the first campaign of dedicated solar observations undertaken by the \textit{Nuclear Spectroscopic Telescope ARray} ({\em NuSTAR}) hard X-ray telescope. Designed as an astrophysics mission, {\em NuSTAR} nonetheless has the capability of directly imaging the Sun at hard X-ray energies ($>$3~keV) with an increase in sensitivity of at least two magnitude compared to current non-focusing telescopes. In this paper we describe the scientific areas where \textit{NuSTAR} will make major improvements on existing solar measurements. We report on the techniques used to observe the Sun with \textit{NuSTAR}, their limitations and complications, and the procedures developed to optimize solar data quality derived from our experience with the initial solar observations. These first observations are briefly described, including the measurement of the Fe K-shell lines in a decaying X-class flare, hard X-ray emission from high in the solar corona, and full-disk hard X-ray images of the Sun.Comment: 11 pages, accepted to Ap

NuSTAR observations of magnetar 1e 1841-045

We report new spectral and temporal observations of the magnetar 1E 1841-045 in the Kes 73 supernova remnant obtained with the Nuclear Spectroscopic Telescope Array. Combined with new Swift and archival XMM-Newton and Chandra observations, the phase-averaged spectrum is well characterized by a blackbody plus double power law, in agreement with previous multimission X-ray results. However, we are unable to reproduce the spectral results reported based on Suzaku observations. The pulsed fraction of the source is found to increase with photon energy. The measured rms pulsed fractions are similar to 12% and similar to 17% at similar to 20 and similar to 50 keV, respectively. We detect a new feature in the 24-35 keV band pulse profile that is uniquely double peaked. This feature may be associated with a possible absorption or emission feature in the phase-resolved spectrum. We fit the X-ray data using the recently developed electron-positron outflow model by Beloborodov for the hard X-ray emission from magnetars. This produces a satisfactory fit, allowing a constraint on the angle between the rotation and magnetic axes of the neutron star of similar to 20 degrees and on the angle between the rotation axis and line of sight of similar to 50 degrees. In this model, the soft X-ray component is inconsistent with a single blackbody; adding a second blackbody or a power-law component fits the data. The two-blackbody interpretation suggests a hot spot of temperature kT approximate to 0.9 keV occupying similar to 1% of the stellar surface

Timing and flux evolution of the galactic center magnetar SGR J1745–2900

We present the X-ray timing and spectral evolution of the Galactic Center magnetar SGR J1745–2900 for the first ∼4 months post-discovery using data obtained with the Nuclear Spectroscopic Telescope Array and Swift observatories. Our timing analysis reveals a large increase in the magnetar spin-down rate by a factor of 2.60 ± 0.07 over our data span. We further show that the change in spin evolution was likely coincident with a bright X-ray burst observed in 2013 June by Swift, and if so, there was no accompanying discontinuity in the frequency. We find that the source 3-10 keV flux has declined monotonically by a factor of ∼2 over an 80 day period post-outburst accompanied by a ∼20% decrease in the source's blackbody temperature, although there is evidence for both flux and kT having leveled off. We argue that the torque variations are likely to be magnetospheric in nature and will dominate over any dynamical signatures of orbital motion around Sgr A*

Fluorescence Polarization and Fluctuation Analysis Monitors Subunit Proximity, Stoichiometry, and Protein Complex Hydrodynamics

Förster resonance energy transfer (FRET) microscopy is frequently used to study protein interactions and conformational changes in living cells. The utility of FRET is limited by false positive and negative signals. To overcome these limitations we have developed Fluorescence Polarization and Fluctuation Analysis (FPFA), a hybrid single-molecule based method combining time-resolved fluorescence anisotropy (homo-FRET) and fluorescence correlation spectroscopy. Using FPFA, homo-FRET (a 1–10 nm proximity gauge), brightness (a measure of the number of fluorescent subunits in a complex), and correlation time (an attribute sensitive to the mass and shape of a protein complex) can be simultaneously measured. These measurements together rigorously constrain the interpretation of FRET signals. Venus based control-constructs were used to validate FPFA. The utility of FPFA was demonstrated by measuring in living cells the number of subunits in the α-isoform of Venus-tagged calcium-calmodulin dependent protein kinase-II (CaMKIIα) holoenzyme. Brightness analysis revealed that the holoenzyme has, on average, 11.9±1.2 subunit, but values ranged from 10–14 in individual cells. Homo-FRET analysis simultaneously detected that catalytic domains were arranged as dimers in the dodecameric holoenzyme, and this paired organization was confirmed by quantitative hetero-FRET analysis. In freshly prepared cell homogenates FPFA detected only 10.2±1.3 subunits in the holoenzyme with values ranging from 9–12. Despite the reduction in subunit number, catalytic domains were still arranged as pairs in homogenates. Thus, FPFA suggests that while the absolute number of subunits in an auto-inhibited holoenzyme might vary from cell to cell, the organization of catalytic domains into pairs is preserved

Non-aqueous Isorefractive Pickering Emulsions

Non-aqueous Pickering emulsions of 16–240 μm diameter have been prepared using diblock copolymer worms with ethylene glycol as the droplet phase and an n-alkane as the continuous phase. Initial studies using n-dodecane resulted in stable emulsions that were significantly less turbid than conventional water-in-oil emulsions. This is attributed to the rather similar refractive indices of the latter two phases. By utilizing n-tetradecane as an alternative oil that almost precisely matches the refractive index of ethylene glycol, almost isorefractive ethylene glycol-in-n-tetradecane Pickering emulsions can be prepared. The droplet diameter and transparency of such emulsions can be systematically varied by adjusting the worm copolymer concentration

The shared socio-economic pathway (SSP) greenhouse gas concentrations and their extensions to 2500

Anthropogenic increases in atmospheric greenhouse gas concentrations are the main driver of current and future climate change. The integrated assessment community has quantified anthropogenic emissions for the shared socio-economic pathway (SSP) scenarios, each of which represents a different future socio-economic projection and political environment. Here, we provide the greenhouse gas concentrations for these SSP scenarios – using the reduced-complexity climate–carbon-cycle model MAGICC7.0. We extend historical, observationally based concentration data with SSP concentration projections from 2015 to 2500 for 43 greenhouse gases with monthly and latitudinal resolution. CO2 concentrations by 2100 range from 393 to 1135 ppm for the lowest (SSP1-1.9) and highest (SSP5-8.5) emission scenarios, respectively. We also provide the concentration extensions beyond 2100 based on assumptions regarding the trajectories of fossil fuels and land use change emissions, net negative emissions, and the fraction of non-CO2 emissions. By 2150, CO2 concentrations in the lowest emission scenario are approximately 350 ppm and approximately plateau at that level until 2500, whereas the highest fossil-fuel-driven scenario projects CO2 concentrations of 1737 ppm and reaches concentrations beyond 2000 ppm by 2250. We estimate that the share of CO2 in the total radiative forcing contribution of all considered 43 long-lived greenhouse gases increases from 66 % for the present day to roughly 68 % to 85 % by the time of maximum forcing in the 21st century. For this estimation, we updated simple radiative forcing parameterizations that reflect the Oslo Line-By-Line model results. In comparison to the representative concentration pathways (RCPs), the five main SSPs (SSP1-1.9, SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) are more evenly spaced and extend to lower 2100 radiative forcing and temperatures. Performing two pairs of six-member historical ensembles with CESM1.2.2, we estimate the effect on surface air temperatures of applying latitudinally and seasonally resolved GHG concentrations. We find that the ensemble differences in the March–April–May (MAM) season provide a regional warming in higher northern latitudes of up to 0.4 K over the historical period, latitudinally averaged of about 0.1 K, which we estimate to be comparable to the upper bound (∼5 % level) of natural variability. In comparison to the comparatively straight line of the last 2000 years, the greenhouse gas concentrations since the onset of the industrial period and this studies' projections over the next 100 to 500 years unequivocally depict a “hockey-stick” upwards shape. The SSP concentration time series derived in this study provide a harmonized set of input assumptions for long-term climate science analysis; they also provide an indication of the wide set of futures that societal developments and policy implementations can lead to – ranging from multiple degrees of future warming on the one side to approximately 1.5 ∘C warming on the other

The Orphan Gene ybjN Conveys Pleiotropic Effects on Multicellular Behavior and Survival of Escherichia coli

YbjN, encoding an enterobacteria-specific protein, is a multicopy suppressor of temperature sensitivity in the ts9 mutant strain of Escherichia coli. In this study, we further explored the role(s) of ybjN. First, we demonstrated that the ybjN transcript was about 10-fold lower in the ts9 strain compared to that of E. coli strain BW25113 (BW). Introduction of multiple copies of ybjN in the ts9 strain resulted in over-expression of ybjN by about 10-fold as compared to that of BW. These results suggested that temperature sensitivity of the ts9 mutant of E. coli may be related to expression levels of ybjN. Characterization of E. coli ybjN mutant revealed that ybjN mutation resulted in pleiotropic phenotypes, including increased motility, fimbriation (auto-aggregation), exopolysaccharide production, and biofilm formation. In contrast, over-expression of ybjN (in terms of multiple copies) resulted in reduced motility, fimbriation, exopolysaccharide production, biofilm formation and acid resistance. In addition, our results indicate that a ybjN-homolog gene from Erwinia amylovora, a plant enterobacterial pathogen, is functionally conserved with that of E. coli, suggesting similar evolution of the YbjN family proteins in enterobacteria. A microarray study revealed that the expression level of ybjN was inversely correlated with the expression of flagellar, fimbrial and acid resistance genes. Over-expression of ybjN significantly down-regulated genes involved in citric acid cycle, glycolysis, the glyoxylate shunt, oxidative phosphorylation, amino acid and nucleotide metabolism. Furthermore, over-expression of ybjN up-regulated toxin-antitoxin modules, the SOS response pathway, cold shock and starvation induced transporter genes. Collectively, these results suggest that YbjN may play important roles in regulating bacterial multicellular behavior, metabolism, and survival under stress conditions in E. coli. These results also suggest that ybjN over-expression-related temperature rescue of the ts9 mutant may be due to down-regulation of metabolic activity and activation of stress response genes in the ts9 mutant