The physical mechanism driving mass ejection during a nova eruption is still poorly understood. Possibilities include ejection in a single ballistic event, a common-envelope interaction, a continuous ...wind, or some combination of these processes. Here, we present a study of 12 Galactic novae, for which we have premaximum high-resolution spectroscopy. All 12 novae show the same spectral evolution. Before optical peak, they show a slow P Cygni component. After peak, a fast component quickly arises, while the slow absorption remains superimposed on top of it, implying the presence of at least two physically distinct flows. For novae with high-cadence monitoring, a third, intermediate-velocity component is also observed. These observations are consistent with a scenario where the slow component is associated with the initial ejection of the accreted material and the fast component with a radiation-driven wind from the white dwarf. When these flows interact, the slow flow is swept up by the fast flow, producing the intermediate component. These colliding flows may produce theγ-ray emission observed in some novae. Our spectra also show that the transient heavy-element absorption lines seen in some novae have the same velocity structure and evolution as the other lines in the spectrum, implying an association with the nova ejecta rather than a preexisting circumbinary reservoir of gas or material ablated from the secondary. While this basic scenario appears to qualitatively reproduce multiwavelength observations of classical novae, substantial theoretical and observational work is still needed to untangle the rich diversity of nova properties.
Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake of glutamine and ...subsequent glutaminolysis is critical for activation of the mTORC1 nutrient-sensing pathway, which regulates cell growth and protein translation in cancer cells. This is of particular interest in breast cancer, as glutamine dependence is increased in high-risk breast cancer subtypes. Pharmacological inhibitors of ASCT2-mediated transport significantly reduced glutamine uptake in human breast cancer cell lines, leading to the suppression of mTORC1 signalling, cell growth and cell cycle progression. Notably, these effects were subtype-dependent, with ASCT2 transport critical only for triple-negative (TN) basal-like breast cancer cell growth compared with minimal effects in luminal breast cancer cells. Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. Using a bioluminescent orthotopic xenograft mouse model, ASCT2 expression was then shown to be necessary for both successful engraftment and growth of HCC1806 TN breast cancer cells in vivo. Lower tumoral expression of ASCT2 conferred a significant survival advantage in xenografted mice. These responses remained intact in primary breast cancers, where gene expression analysis showed high expression of ASCT2 and glutamine metabolism-related genes, including GLUL and GLS, in a cohort of 90 TN breast cancer patients, as well as correlations with the transcriptional regulators, MYC and ATF4. This study provides preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of ASCT2, but also a marked reliance on its activity for sustained cellular proliferation.
Objective To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months ...and ameliorates the negative effects of the episode on physical performance and health status.Design Prospective, randomised controlled trial.Setting An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom.Participants 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193).Main outcome measures The primary outcome was readmission rate at 12 months. Secondary outcomes included number of hospital days, mortality, physical performance, and health status. The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome.Interventions Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission. The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training. Patients also received a self management and education package.Results Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group). No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4). An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03). Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year.Conclusion Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months. Mortality at 12 months was higher in the intervention group. The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness.Trial registration Current Controlled Trials ISRCTN05557928.
Electrical brain signals are often decomposed into frequency ranges that are implicated in different functions. Using subdural electrocorticography (ECoG, intracranial EEG) and functional magnetic ...resonance imaging (fMRI), we measured frequency spectra and BOLD responses in primary visual cortex (V1) and intraparietal sulcus (IPS). In V1 and IPS, 30–120Hz (gamma, broadband) oscillations allowed population receptive field (pRF) reconstruction comparable to fMRI estimates. Lower frequencies, however, responded very differently in V1 and IPS. In V1, broadband activity extends down to 3Hz. In the 4–7Hz (theta) and 18–30Hz (beta) ranges broadband activity increases power during stimulation within the pRF. However, V1 9–12Hz (alpha) frequency oscillations showed a different time course. The broadband power here is exceeded by a frequency-specific power increase during stimulation of the area outside the pRF. As such, V1 alpha oscillations reflected surround suppression of the pRF, much like negative fMRI responses. They were consequently highly localized, depending on stimulus and pRF position, and independent between nearby electrodes. In IPS, all 3–25Hz oscillations were strongest during baseline recording and correlated between nearby electrodes, consistent with large-scale disengagement. These findings demonstrate V1 alpha oscillations result from locally active functional processes and relate these alpha oscillations to negative fMRI signals. They highlight that similar oscillations in different areas reflect processes with different functional roles. However, both of these roles of alpha seem to reflect suppression of spiking activity.
► γ-Oscillations increase similarly during receptive field stimulation in V1 and IPS. ► V1 α-oscillations are local and reflect surround inhibition and negative fMRI signals. ► IPS slow oscillations, including α, reflect non-local large-scale disengagement. ► Similar oscillations in different visual areas have different roles.
Since the Iowa 500 study, residential and occupational status have been frequently used as indicators of everyday achievements in research on schizophrenia and bipolar disorder. The relationships of ...residential and occupational status with impairment in multiple domains including physical health indicators across these two diagnoses, however, have rarely been studied. We examined these relationships at the 20-year follow-up assessment of a first-admission sample.
We included 146 participants with schizophrenia and 87 with bipolar disorder with psychosis who participated in the 20-year follow-up of the Suffolk County Mental Health Project. In addition to interviewer-based ratings of employment and residential independence, we examined self-reported impairment derived from the WHODAS, standard measures of current psychopathology, indicators of obesity, as well as performance-based measures of physical and cognitive functioning.
Participants with bipolar disorder were more likely to live independently and be gainfully employed; they also performed significantly better on each indicator of impairment apart from balance ability. In both groups, unemployment, but not residential independence, was associated with greater self-reported disability on the WHODAS. Residential independence, gainful employment, and subjective disability were also associated with better physical functioning. Across the two groups, psychiatric symptoms and physical functioning were the major determinants of subjective disability.
People with psychotic bipolar disorder were more likely to be gainfully employed and living independently than participants with schizophrenia but as a group, much less frequently than population standards. Interventions aimed at physical fitness may have the potential to improve both objective functioning and perceived disability.
Abstract
Many radio galaxies show the presence of dense and dusty gas near the active nucleus. This can be traced by both 21 cm H i absorption and soft X-ray absorption, offering new insight into the ...physical nature of the circumnuclear medium of these distant galaxies. To better understand this relationship, we investigate soft X-ray absorption as an indicator for the detection of associated H i absorption, as part of preparation for the First Large Absorption Survey in H i to be undertaken with the Australian Square Kilometre Array Pathfinder (ASKAP). We present the results of our pilot study using the Boolardy Engineering Test Array, a precursor to ASKAP, to search for new absorption detections in radio sources brighter than 1 Jy that also feature soft X-ray absorption. Based on this pilot survey, we detected H i absorption towards the radio source PKS 1657−298 at a redshift of z = 0.42. This source also features the highest X-ray absorption ratio of our pilot sample by a factor of 3, which is consistent with our general findings that X-ray absorption predicates the presence of dense neutral gas. By comparing the X-ray properties of active galactic nuclei with and without detection of H i absorption at radio wavelengths, we find that X-ray hardness ratio and H i absorption optical depth are correlated at a statistical significance of 4.71σ. We conclude by considering the impact of these findings on future radio and X-ray absorption studies.
Context. Classical novae are eruptions on the surface of a white dwarf in a binary system. The material ejected from the white dwarf surface generally forms an axisymmetric shell of gas and dust ...around the system. The three-dimensional structure of these shells is difficult to untangle when viewed on the plane of the sky. In this work a geometrical model is developed to explain new observations of the 2015 nova V5668 Sagittarii. Aim. We aim to better understand the early evolution of classical nova shells in the context of the relationship between polarisation, photometry, and spectroscopy in the optical regime. To understand the ionisation structure in terms of the nova shell morphology and estimate the emission distribution directly following the light curve’s dust-dip. Methods. High-cadence optical polarimetry and spectroscopy observations of a nova are presented. The ejecta is modelled in terms of morpho-kinematics and photoionisation structure. Results. Initially observational results are presented, including broadband polarimetry and spectroscopy of V5668 Sgr nova during eruption. Variability over these observations provides clues towards the evolving structure of the nova shell. The position angle of the shell is derived from polarimetry, which is attributed to scattering from small dust grains. Shocks in the nova outflow are suggested in the photometry and the effect of these on the nova shell are illustrated with various physical diagnostics. Changes in density and temperature as the super soft source phase of the nova began are discussed. Gas densities are found to be of the order of 109 cm−3 for the nova in its auroral phase. The blackbody temperature of the central stellar system is estimated to be around 2.2 × 105 K at times coincident with the super soft source turn-on. It was found that the blend around 4640 Å commonly called “nitrogen flaring” is more naturally explained as flaring of the O II multiplet (V1) from 4638–4696 Å, i.e. “oxygen flaring”. Conclusions. V5668 Sgr (2015) was a remarkable nova of the DQ Her class. Changes in absolute polarimetric and spectroscopic multi-epoch observations lead to interpretations of physical characteristics of the nova’s evolving outflow. The high densities that were found early-on combined with knowledge of the system’s behaviour at other wavelengths and polarimetric measurements strongly suggest that the visual “cusps” are due to radiative shocks between fast and slow ejecta that destroy and create dust seed nuclei cyclically.
The functional repair of large skeletal defects remains a significant challenge to orthopaedic surgeons due to the lack of effective strategies to promote bone regeneration, particularly in the ...elderly. This study investigated the potential use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4-month-old donor mice were seeded in type I collagen gels that were then compressed to form scaffolds with a fibrillar density similar to osteoid. The cells remained metabolically active in scaffolds incubated in vitro for up to 15 days and differentiated into osteoblasts that deposited calcium-phosphate mineral into the scaffold, which was quantified using micro-computed tomographic (micro-CT) imaging. When implanted in a 1 mm x 3 mm unicortical defect the MSC-loaded scaffolds were rapidly mineralised and integrated into host bone with administration of 10 ng of recombinant VEGF injected into the femoral canal at 4 days postoperative. Empty scaffolds and MSC-seeded scaffolds implanted in defects that did not receive a bolus dose of VEGF did not mineralise or integrate with native bone. The approach with MSC, hydrogels and a biologic factor already approved for human use warrants further pre-clinical investigation with a large animal model.
Summary
Fracture-related costs vary by country. A standardized methodology and presentations were proposed to fairly assess the economic burden of osteoporotic fracture. Results indicated substantial ...costs of osteoporotic fractures for pharmacy, hospitalization, emergency care, and outpatient visits in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA.
Purpose
The objective of this multinational, retrospective matched cohort study was to use a standardized methodology across different healthcare systems to estimate the burden of osteoporotic fracture (OF) in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA.
Methods
Within each country, healthcare resource utilization and direct costs of care were compared between patients with newly identified OF and a propensity score–matched cohort without OF during follow-up periods of up to 5 years.
Results
Across all five countries, the OF cohort had significantly higher rates and length of inpatient admissions compared with the non-OF cohort. In each country, the adjusted total costs of care ratio between OF and non-OF cohorts were significant. The adjusted cost ratios for pharmacy, inpatient care, emergency care, and outpatient visits were similarly higher in the OF cohort across countries.
Conclusion
The current study demonstrates the substantial economic burden of OF across different countries when compared with matched non-OF patients. The findings would assist stakeholders and policymakers in developing appropriate health policies.
The Ganga-Brahmaputra-Meghna (GBM) River System, the associated Hooghly River and the Mahanadi River System represent the largest river basins in the world serving a population of over 780 million. ...The rivers are of vital concern to India and Bangladesh as they provide fresh water for people, agriculture, industry, conservation and support the Delta System in the Bay of Bengal. Future changes in both climate and socio-economics have been investigated to assess whether these will alter river flows and water quality. Climate datasets downscaled from three different Global Climate Models have been used to drive a daily process based flow and water quality model. The results suggest that due to climate change the flows will increase in the monsoon period and also be enhanced in the dry season. However, once socio-economic changes are also considered, increased population, irrigation, water use and industrial development reduce water availability in drought conditions, threatening water supplies and posing a threat to river and coastal ecosystems. This study, as part of the DECCMA (Deltas, vulnerability and Climate Change: Migration and Adaptation) project, also addresses water quality issues, particularly nutrients (N and P) and their transport along the rivers and discharge into the Delta System. Climate will alter flows, increasing flood flows and changing pollution dilution factors in the rivers, as well as other key processes controlling water quality. Socio-economic change will affect water quality, as water diversion strategies, increased population and industrial development alter the water balance and enhance fluxes of nutrients from agriculture, urban centers and atmospheric deposition.
The study is set in India and Bangladesh with a focus on the massive catchments of the Ganga and Brahmaputra flowing into the Bay of Bengal Delta system. This system is also impacted by the Meghna River and the Hooghly River with the Mahanadi also delivering flow and nutrients to the Bay of Bengal. Display omitted
•Application of an integrated flow and water quality model to 5 major river systems in India and Bangladesh•Uses 3 new combinations of GCM and RCP models to assess impacts of climate change on streamflow•Evaluates the effects of socioeconomic change on hydrology and water quality•Evaluates combined effects of climate change and socioeconomic change on flow and water quality•Assesses likely change with major water abstractions from the Brahmaputra
PDF
