Mid-Infrared diagnostics of metal-rich HII regions from VLT and Spitzer Spectroscopy of Young Massive Stars in W31

We present near-IR VLT/ISAAC and mid-IR Spitzer/IRS spectroscopy of the young massive cluster in the W31 star-forming region. H-band spectroscopy provides refined classifications for four cluster members O stars with respect to Blum et al. In addition, photospheric features are detected in the massive Young Stellar Object (mYSO) #26. Spectroscopy permits estimates of stellar temperatures and masses, from which a cluster age of ~0.6 Myr and distance of 3.3 kpc are obtained, in excellent agreement with Blum et al. IRS spectroscopy reveals mid-infrared fine structure line fluxes of [Ne II-III] and [S III-IV] for four O stars and five mYSOs. In common with previous studies, stellar temperatures of individual stars are severely underestimated from the observed ratios of fine-structure lines, despite the use of contemporary stellar atmosphere and photoionization models. We construct empirical temperature calibrations based upon the W31 cluster stars of known spectral type, supplemented by two inner Milky Way ultracompact (UC) HII regions whose ionizing star properties are established. Calibrations involving [NeIII] 15.5um/[NeII] 12.8um, [SIV] 10.5um/[NeII] 12.8um or [ArIII] 9.0um/[NeII] 12.8um have application in deducing the spectral types of early- to mid- O stars for other inner Milky Way compact and UCHII regions. Finally, evolutionary phases and timescales for the massive stellar content in W31 are discussed, due to the presence of numerous young massive stars at different formation phases in a `coeval' cluster.Comment: 16 pages, 13 figures, accepted for MNRA

Shoulder posture and median nerve sliding

Background: Patients with upper limb pain often have a slumped sitting position and poorshoulder posture. Pain could be due to poor posture causing mechanical changes (stretch; localpressure) that in turn affect the function of major limb nerves (e.g. median nerve). This studyexamines (1) whether the individual components of slumped sitting (forward head position, trunkflexion and shoulder protraction) cause median nerve stretch and (2) whether shoulderprotraction restricts normal nerve movements.Methods: Longitudinal nerve movement was measured using frame-by-frame cross-correlationanalysis from high frequency ultrasound images during individual components of slumped sitting.The effects of protraction on nerve movement through the shoulder region were investigated byexamining nerve movement in the arm in response to contralateral neck side flexion.Results: Neither moving the head forward or trunk flexion caused significant movement of themedian nerve. In contrast, 4.3 mm of movement, adding 0.7% strain, occurred in the forearm duringshoulder protraction. A delay in movement at the start of protraction and straightening of thenerve trunk provided evidence of unloading with the shoulder flexed and elbow extended and thescapulothoracic joint in neutral. There was a 60% reduction in nerve movement in the arm duringcontralateral neck side flexion when the shoulder was protracted compared to scapulothoracicneutral.Conclusion: Slumped sitting is unlikely to increase nerve strain sufficient to cause changes tonerve function. However, shoulder protraction may place the median nerve at risk of injury, sincenerve movement is reduced through the shoulder region when the shoulder is protracted andother joints are moved. Both altered nerve dynamics in response to moving other joints and localchanges to blood supply may adversely affect nerve function and increase the risk of developingupper quadrant pain

Eta carinae and the homunculus: far infrared/submillimetre spectral lines detected with the Herschel Space Observatory

The evolved massive binary star η Carinae underwent eruptive mass-loss events that formed the complex bi-polar ‘Homunculus’ nebula harbouring tens of solar masses of unusually nitrogen-rich gas and dust. Despite expectations for the presence of a significant molecular component to the gas, detections have been observationally challenged by limited access to the far-infrared and the intense thermal continuum. A spectral survey of the atomic and rotational molecular transitions was carried out with the Herschel Space Observatory, revealing a rich spectrum of broad emission lines originating in the ejecta. Velocity profiles of selected PACS lines correlate well with known substructures: H I in the central core; NH and weak [C II] within the Homunculus; and [N II] emissions in fast-moving structures external to the Homunculus. We have identified transitions from [O I], H I, and 18 separate light C- and O-bearing molecules including CO, CH, CH+, and OH, and a wide set of N-bearing molecules: NH, NH+, N2H+, NH2, NH3, HCN, HNC, CN, and N2H+. Half of these are new detections unprecedented for any early-type massive star environment. A very low ratio [12C/13C] ≤ 4 is estimated from five molecules and their isotopologues. We demonstrate that non-LTE effects due to the strong continuum are significant. Abundance patterns are consistent with line formation in regions of carbon and oxygen depletions with nitrogen enhancements, reflecting an evolved state of the erupting star with efficient transport of CNO-processed material to the outer layers. The results offer many opportunities for further observational and theoretical investigations of the molecular chemistry under extreme physical and chemical conditions around massive stars in their final stages of evolution

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease.

BACKGROUND: In clinical trials of inhaled bronchodilators, chronic obstructive pulmonary disease (COPD) guidelines recommend that patient-reported outcomes (PROs) are assessed alongside lung function. How these endpoints are related is unclear. METHODS: Pooled longitudinal data from 23 randomised controlled COPD studies were analyzed (N = 23,213). Treatments included long-acting β2 agonists, long-acting muscarinic antagonists (LABAs or LAMAs) and the LABA/LAMA combination QVA149. Outcome measures were Transition Dyspnoea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ) scores, COPD exacerbation frequency and rescue medication use. Relationships between changes in trough forced expiratory volume in one second (ΔFEV1) and outcomes following treatment were assessed using correlations of data summaries and model-based analysis: generalized linear mixed-effect regression modeling to determine if ΔFEV1 could predict patient outcomes with different treatments. RESULTS: Mean age was 64 years, 73% were male, and most had moderate (45%) or severe (52%) disease. Statistically significant correlations were observed between ΔFEV1 and each outcome measure (exacerbations Rs = 0.05; rescue medication, SGRQ, TDI, r = 0.11-0.16; all p < .001). Patients with greater improvements in trough FEV1 had on average better SGRQ and TDI scores, fewer exacerbations, and used less rescue medication. For SGRQ and TDI scores, minimal clinically important differences were observed over the range of pooled ΔFEV1 values. Model-based predictions confirmed the treatment effect was partly explained by changes in FEV1 from baseline with improvements in PROs observed across all treatments when trough FEV1 improved. Across all endpoints active treatments were better than placebo (p < .0001), and LABA/LAMA treatment resulted in numerically better treatment outcomes than either monocomponent. CONCLUSIONS: These data suggest that FEV1 improvements post-bronchodilation correlate with PRO improvements. Further improvements in patient outcomes may be expected by maximizing lung function improvements. TRIAL REGISTRATION: Registration details for the 23 randomised controlled studies used in this pooled analysis are supplied in Additional File 4

Infrared imaging and spectroscopy of the Luminous Blue Variables Wra 751 and AG Car

We present ground-based infrared imaging and ISO spectroscopy of the luminous blue variables Wra 751 and AG Car. The images show in both cases a detached shell with a roughly circular distribution of emission. The infrared images of AG Car coincide very well with the optical images. The optical (H[FORMULA]) image of Wra 751 is different from the infrared image; the H[FORMULA] nebula is suggested to be a scattering nebula containing cold dust particles. Fitting both the images and the spectra consistently with a 1-D radiative transfer model, we derive properties of their dust shells. Wra 751 is surrounded by a dust shell with inner and outer radii of 0.17 and 0.34 pc respectively and a dust mass of 0.017 [FORMULA]. The dust shell of AG Car has inner and outer radii of 0.37 and 0.81 pc respectively and a total dust mass of 0.25 [FORMULA]. Dust mass-loss rates during the formation of the shells are 2.7[FORMULA] and 3.4[FORMULA] [FORMULA] yr-1, respectively. The total dust mass and hence the derived dust mass-loss rates are uncertain by at least a factor of two. For AG Car, the derived dust mass and mass-loss rate are higher than previous estimates. This is mainly caused by the fact that a contribution of very large grains ([FORMULA] 10 µm) is needed to explain the flux levels at longer wavelengths. Dust models for both objects fail to explain the flux shortward of 15 to 20 µm: a population of small warm grains, not in thermal equilibrium with the central star is necessary to explain this excess. Similarities between dust shells around Wolf-Rayet stars and Wra 751 and AG Car (mass, grain size population, morphology) suggest a similar formation history and imply an evolutionary connection. A similar connection with red supergiants is suggested on the basis of the dust composition and derived time-averaged mass-loss rates

Comparison Between Diffusion-Weighted MRI and I-123-mIBG Uptake in Primary High-Risk Neuroblastoma

Background: High-risk neuroblastoma (HR-NB) has a variable response to preoperative chemotherapy. It is not possible to differentiate viable vs. nonviable residual tumor before surgery. Purpose: To explore the association between apparent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI), 123I-meta-iodobenzyl-guanidine (123I-mIBG) uptake, and histology before and after chemotherapy. Study Type: Retrospective. Subjects: Forty patients with HR-NB. Field Strength/Sequence: 1.5T axial DW-MRI (b = 0,1000 s/mm2 ) and T2-weighted sequences. 123I-mIBG scintigraphy planar imaging (all patients), with additional 123I-mIBG single-photon emission computed tomography / computerized tomography (SPECT/CT) imaging (15 patients). Assessment: ADC maps and 123I-mIBG SPECT/CT images were coregistered to the T2-weighted images. 123I-mIBG uptake was normalized with a tumor-to-liver count ratio (TLCR). Regions of interest (ROIs) for primary tumor volume and different intratumor subregions were drawn. The lower quartile ADC value (ADC25prc) was used over the entire tumor volume and the overall level of 123I-mIBG uptake was graded into avidity groups. Statistical Tests: Analysis of variance (ANOVA) and linear regression were used to compare ADC and MIBG values before and after treatment. Threshold values to classify tumors as viable/necrotic were obtained using ROC analysis of ADC and TLCR values. Results: No significant difference in whole-tumor ADC25prc values were found between different 123I-mIBG avidity groups pre- (P = 0.31) or postchemotherapy (P = 0.35). In the “intratumor” analysis, 5/15 patients (prechemotherapy) and 0/14 patients (postchemotherapy) showed a significant correlation between ADC and TLCR values (P < 0.05). Increased tumor shrinkage was associated with lower pretreatment tumor ADC25prc values (P < 0.001); no association was found with pretreatment 123I-mIBG avidity (P = 0.17). Completely nonviable tumors had significantly lower postchemotherapy ADC25prc values than tumors with >10% viable tumor (P < 0.05). Both pre- and posttreatment TLCR values were significantly higher in patients with >50% viable tumor than those with 10–50% viable tumor (P < 0.05). Data Conclusion: 123I-mIBG avidity and ADC values are complementary noninvasive biomarkers of therapeutic response in HR-NB. Level of Evidence: 4. Technical Efficacy Stage: 3

Mid-infrared evolution of eta Carinae from 1968 to 2018

η Car is one of the most luminous and massive stars in our Galaxy and is the brightest mid-IR source in the sky outside our solar system. Since the late 1990s, the central source has dramatically brightened at UV and optical wavelengths. This might be explained by a decrease in circumstellar dust extinction. We aim to establish the mid-IR flux evolution and further our understanding of the star’s UV and optical brightening. Mid-IR images from 8−20 µm were obtained in 2018 with VISIR at the Very Large Telescope. Archival data from 2003 and 2005 were retrieved from the ESO Science Archive Facility, and historical records were collected from publications. We present mid-IR images of η Car with the highest angular resolution to date at the corresponding wavelengths (≥0.2200). We reconstruct the mid-IR evolution of the spectral energy distribution of the spatially integrated Homunculus nebula from 1968 to 2018 and find no long-term changes. The bolometric luminosity of η Car has been stable over the past five decades. We do not observe a long-term decrease in the mid-IR flux densities that could be associated with the brightening at UV and optical wavelengths, but circumstellar dust must be declining in our line of sight alone. Short-term flux variations within about 25% of the mean levels could be present

A new mouse line with reduced GluA2 Q/R site RNA editing exhibits loss of dendritic spines, hippocampal CA1-neuron loss, learning and memory impairments and NMDA receptor-independent seizure vulnerability.

Calcium (Ca2+)-permeable AMPA receptors may, in certain circumstances, contribute to normal synaptic plasticity or to neurodegeneration. AMPA receptors are Ca2+-permeable if they lack the GluA2 subunit or if GluA2 is unedited at a single nucleic acid, known as the Q/R site. In this study, we examined mice engineered with a point mutation in the intronic editing complementary sequence (ECS) of the GluA2 gene, Gria2. Mice heterozygous for the ECS mutation (named GluA2+/ECS(G)) had a ~ 20% reduction in GluA2 RNA editing at the Q/R site. We conducted an initial phenotypic analysis of these mice, finding altered current-voltage relations (confirming expression of Ca2+-permeable AMPA receptors at the synapse). Anatomically, we observed a loss of hippocampal CA1 neurons, altered dendritic morphology and reductions in CA1 pyramidal cell spine density. Behaviourally, GluA2+/ECS(G) mice exhibited reduced motor coordination, and learning and memory impairments. Notably, the mice also exhibited both NMDA receptor-independent long-term potentiation (LTP) and vulnerability to NMDA receptor-independent seizures. These NMDA receptor-independent seizures were rescued by the Ca2+-permeable AMPA receptor antagonist IEM-1460. In summary, unedited GluA2(Q) may have the potential to drive NMDA receptor-independent processes in brain function and disease. Our study provides an initial characterisation of a new mouse model for studying the role of unedited GluA2(Q) in synaptic and dendritic spine plasticity in disorders where unedited GluA2(Q), synapse loss, neurodegeneration, behavioural impairments and/or seizures are observed, such as ischemia, seizures and epilepsy, Huntington's disease, amyotrophic lateral sclerosis, astrocytoma, cocaine seeking behaviour and Alzheimer's disease

Whisker touch guides canopy exploration in a nocturnal, arboreal rodent, the Hazel dormouse (Muscardinus avellanarius)

Dormouse numbers are declining in the UK due to habitat loss and fragmentation. We know that dormice are nocturnal, arboreal, and avoid crossing open spaces between habitats, yet how they navigate around their canopy is unknown. As other rodents use whisker touch sensing to navigate and explore their environment, this study investigates whether Hazel dormice (Muscardinus avellanarius) employ their whiskers to cross between habitats. We analysed high-speed video footage of dormice exploring freely in flat and climbing arenas in near darkness and using infrared light illumination. We confirm that, like rats and mice, dormice move their whiskers back and forth continuously (~10 Hz) in a motion called whisking and recruit them to explore small gaps (<10 cm) by increasing the amplitude and frequency of whisking and also the asymmetry of movement between the left and right whisker fields. When gaps between platforms are larger than 10-15 cm dormice spend more time travelling on the floor. These findings suggest that dormice can actively and purposively move their whiskers to gather relevant information from their canopy at night. As this species is vulnerable to threats on the ground, we also provide evidence that joining habitat patches between dormouse populations is important for promoting natural behaviours and movement between patches