How do informal self-care strategies evolve among patients with chronic obstructive pulmonary disease managed in primary care? A qualitative study

Background: There is much description in the literature of how patients with chronic obstructive pulmonary disease (COPD) manage their breathlessness and engage in self-care activities; however, little of this is from the perspective of those with less severe disease, who are primarily managed in primary care. This study aimed to understand the self-care experiences of patients with COPD who are primarily managed in primary care, and to examine the challenges of engaging in such behaviors. Methods: Semistructured interviews were carried out with 15 patients with COPD as part of a larger project evaluating a self-management intervention. Thematic analysis was supported by NVivo software (version 8, QSR International, Melbourne, Australia). Results: Three main themes are described, ie, experiencing and understanding symptoms of COPD, current self-care activities, and the importance of family perceptions in managing COPD. Conclusion: Self-care activities evolved spontaneously as participants experienced symptoms of COPD. However, there was a lack of awareness about whether these strategies would impact upon symptoms. Perceptions of COPD by family members posed a challenge to self-care for some participants. Health care professionals should elicit patients' prior disease experiences and utilize spontaneous attempts at disease management in future self-management. These findings have implications for promoting self-management and enhancing quality of life

Optimal Hypercontractivity for Fermi Fields and Related Non-Commutative Integration

Optimal hypercontractivity bounds for the fermion oscillator semigroup are obtained. These are the fermion analogs of the optimal hypercontractivity bounds for the boson oscillator semigroup obtained by Nelson. In the process, several results of independent interest in the theory of non-commutative integration are established. {}.Comment: 18 p., princeton/ecel/7-12-9

Fibrin gel enhances the antitumor effects of chimeric antigen receptor T cells in glioblastoma

Regional delivery of chimeric antigen receptor (CAR) T cells in glioblastoma represents a rational therapeutic approach as an alternative to intravenous administration to avoid the blood-brain barrier impediment. Here, we developed a fibrin gel that accommodates CAR-T cell loading and promotes their gradual release. Using a model of subtotal glioblastoma resection, we demonstrated that the fibrin-based gel delivery of CAR-T cells within the surgical cavity enables superior antitumor activity compared to CAR-T cells directly inoculated into the tumor resection cavity

A multi-species synthesis of physiological mechanisms in drought-induced tree mortality

Widespread tree mortality associated with drought 92 has been observed on all forested continents, and global change is expected to exacerbate vegetation vulnerability. Forest mortality has implications for future biosphere-atmosphere interactions of carbon, water, and energy balance, and is poorly represented in dynamic vegetation models. Reducing uncertainty requires improved mortality projections founded on robust physiological processes. However, the proposed mechanisms of drought-induced mortality, including hydraulic failure and carbon starvation, are unresolved. A growing number of empirical studies have investigated these mechanisms, but data have not been consistently analyzed across species and biomes using a standardized physiological framework. Here we show that xylem hydraulic failure was ubiquitous across multiple tree taxa at drought induced mortality. All species assessed had 60% or higher loss of xylem hydraulic conductivity, consistent with proposed theoretical and modelled survival thresholds. We found diverse responses in non-structural carbohydrate reserves at mortality, indicating that evidence supporting carbon starvation was not universal. Reduced non-structural carbohydrates were more common for gymnosperms than angiosperms, associated with xylem hydraulic vulnerability, and may have a role in reducing hydraulic function. Our finding that hydraulic failure at drought-induced mortality was persistent across species indicates that substantial improvement in vegetation modelling can be achieved using thresholds in hydraulic function

A multi-species synthesis of physiological mechanisms in drought-induced tree mortality

Widespread tree mortality associated with drought 92 has been observed on all forested continents, and global change is expected to exacerbate vegetation vulnerability. Forest mortality has implications for future biosphere-atmosphere interactions of carbon, water, and energy balance, and is poorly represented in dynamic vegetation models. Reducing uncertainty requires improved mortality projections founded on robust physiological processes. However, the proposed mechanisms of drought-induced mortality, including hydraulic failure and carbon starvation, are unresolved. A growing number of empirical studies have investigated these mechanisms, but data have not been consistently analyzed across species and biomes using a standardized physiological framework. Here we show that xylem hydraulic failure was ubiquitous across multiple tree taxa at drought induced mortality. All species assessed had 60% or higher loss of xylem hydraulic conductivity, consistent with proposed theoretical and modelled survival thresholds. We found diverse responses in non-structural carbohydrate reserves at mortality, indicating that evidence supporting carbon starvation was not universal. Reduced non-structural carbohydrates were more common for gymnosperms than angiosperms, associated with xylem hydraulic vulnerability, and may have a role in reducing hydraulic function. Our finding that hydraulic failure at drought-induced mortality was persistent across species indicates that substantial improvement in vegetation modelling can be achieved using thresholds in hydraulic function

A p53-TLR3 axis ameliorates pulmonary hypertension by inducing BMPR2 via IRF3

Pulmonary arterial hypertension (PAH) features pathogenic and abnormal endothelial cells (ECs), and one potential origin is clonal selection. We studied the role of p53 and toll-like receptor 3 (TLR3) in clonal expansion and pulmonary hypertension (PH) via regulation of bone morphogenetic protein (BMPR2) signaling. ECs of PAH patients had reduced p53 expression. EC-specific p53 knockout exaggerated PH, and clonal expansion reduced p53 and TLR3 expression in rat lung CD117+ ECs. Reduced p53 degradation (Nutlin 3a) abolished clonal EC expansion, induced TLR3 and BMPR2, and ameliorated PH. Polyinosinic/polycytidylic acid [Poly(I:C)] increased BMPR2 signaling in ECs via enhanced binding of interferon regulatory factor-3 (IRF3) to the BMPR2 promoter and reduced PH in p53−/− mice but not in mice with impaired TLR3 downstream signaling. Our data show that a p53/TLR3/IRF3 axis regulates BMPR2 expression and signaling in ECs. This link can be exploited for therapy of PH

Cosmological Constraints from Measurements of Type Ia Supernovae Discovered during the First 1.5 yr of the Pan-STARRS1 Survey

We present griz P1 light curves of 146 spectroscopically confirmed Type Ia supernovae (SNe Ia; 0.03 < z < 0.65) discovered during the first 1.5 yr of the Pan-STARRS1 Medium Deep Survey. The Pan-STARRS1 natural photometric system is determined by a combination of on-site measurements of the instrument response function and observations of spectrophotometric standard stars. We find that the systematic uncertainties in the photometric system are currently 1.2% without accounting for the uncertainty in the Hubble Space Telescope Calspec definition of the AB system. A Hubble diagram is constructed with a subset of 113 out of 146 SNe Ia that pass our light curve quality cuts. The cosmological fit to 310 SNe Ia (113 PS1 SNe Ia + 222 light curves from 197 low-z SNe Ia), using only supernovae (SNe) and assuming a constant dark energy equation of state and flatness, yields $w=-1.120^{+0.360}_{-0.206}\hbox{(Stat)} ^{+0.269}_{-0.291}\hbox{(Sys)}$. When combined with BAO+CMB(Planck)+H 0, the analysis yields $\Omega _{\rm M}=0.280^{+0.013}_{-0.012}$ and $w=-1.166^{+0.072}_{-0.069}$ including all identified systematics. The value of w is inconsistent with the cosmological constant value of –1 at the 2.3σ level. Tension endures after removing either the baryon acoustic oscillation (BAO) or the H 0 constraint, though it is strongest when including the H 0 constraint. If we include WMAP9 cosmic microwave background (CMB) constraints instead of those from Planck, we find $w=-1.124^{+0.083}_{-0.065}$, which diminishes the discord to <2σ. We cannot conclude whether the tension with flat ΛCDM is a feature of dark energy, new physics, or a combination of chance and systematic errors. The full Pan-STARRS1 SN sample with ~three times as many SNe should provide more conclusive results

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes