Dill extract induces elastic fiber neosynthesis and functional improvement in the ascending aorta of aged mice with reversal of age-dependent cardiac hypertrophy and involvement of lysyl oxidase-like-1

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin fibroblasts to increase lysyl oxidase-like-1 (LOXL-1) gene expression, an enzyme contributing to tropoelastin crosslinking and elastin formation. Here, we have investigated the effects of a chronic treatment (three months) of aged male mice with DE (5% or 10

Telemedicine Critical Care-Mediated Mortality Reductions in Lower-Performing Patient Diagnosis Groups: A Prospective, Before and After Study

OBJECTIVES: Studies evaluating telemedicine critical care (TCC) have shown mixed results. We prospectively evaluated the impact of TCC implementation on risk-adjusted mortality among patients stratified by pre-TCC performance. DESIGN: Prospective, observational, before and after study. SETTING: Three adult ICUs at an academic medical center. PATIENTS: A total of 2,429 patients in the pre-TCC (January to June 2016) and 12,479 patients in the post-TCC (January 2017 to June 2019) periods. INTERVENTIONS: TCC implementation which included an acuity-driven workflow targeting an identified “lower-performing” patient group, defined by ICU admission in an Acute Physiology and Chronic Health Evaluation diagnoses category with a pre-TCC standardized mortality ratio (SMR) of greater than 1.5. MEASUREMENTS AND MAIN RESULTS: The primary outcome was risk-adjusted hospital mortality. Risk-adjusted hospital length of stay (HLOS) was also studied. The SMR for the overall ICU population was 0.83 pre-TCC and 0.75 post-TCC, with risk-adjusted mortalities of 10.7% and 9.5% (p = 0.09). In the identified lower-performing patient group, which accounted for 12.6% (n = 307) of pre-TCC and 13.3% (n = 1671) of post-TCC ICU patients, SMR decreased from 1.61 (95% CI, 1.21–2.01) pre-TCC to 1.03 (95% CI, 0.91–1.15) post-TCC, and risk-adjusted mortality decreased from 26.4% to 16.9% (p \u3c 0.001). In the remaining (“higher-performing”) patient group, there was no change in pre- versus post-TCC SMR (0.70 [0.59–0.81] vs 0.69 [0.64–0.73]) or risk-adjusted mortality (8.5% vs 8.4%, p = 0.86). There were no pre- to post-TCC differences in standardized HLOS ratio or risk-adjusted HLOS in the overall cohort or either performance group. CONCLUSIONS: In well-staffed and overall higher-performing ICUs in an academic medical center, Acute Physiology and Chronic Health Evaluation granularity allowed identification of a historically lower-performing patient group that experienced a striking TCC-associated reduction in SMR and risk-adjusted mortality. This study provides additional evidence for the relationship between pre-TCC performance and post-TCC improvement

Clinical effectiveness of a sedation protocol minimizing benzodiazepine infusions and favoring early dexmedetomidine: A before-after study

INTRODUCTION: Randomized controlled trials suggest clinical outcomes may be improved with dexmedetomidine as compared to benzodiazepines, however further study and validation is needed. The objective of this study was to determine the clinical effectiveness of a sedation protocol minimizing benzodiazepine use in favor of early dexmedetomidine. METHODS: This was a before-after study including adult surgical and medical ICU patients requiring mechanical ventilation and continuous sedation for at least 24 hours. The before phase included consecutive patients admitted between April 1 and August 31, 2011. Subsequently, the protocol was modified to minimize use of benzodiazepines in favor of early dexmedetomidine through a multidisciplinary approach and staff education was provided. The after phase included consecutive eligible patients between May 1 and October 31, 2012. RESULTS: 199 patients were included, with 97 patients in the before and 102 in the after phase. Baseline characteristics were well balanced between groups. Use of midazolam as initial sedation (58% vs. 27%, p \u3c 0.0001) or at any point during the ICU stay (76% vs. 48%, p \u3c 0.0001) was significantly reduced in the after phase. Dexmedetomidine use as initial sedation (2% vs. 39%, p \u3c 0.0001) or at any point during the ICU stay (39% vs. 82%, p \u3c 0.0001) significantly increased. Both the prevalence (81% vs. 93%, p =0.013) and median percent of days with delirium (55% (IQR 18-83) vs. 71% (IQR 45-100), p = 0.001) were increased in the after phase. The median duration of mechanical ventilation was significantly reduced in the after phase (110 (IQR 59-192) vs. 74.5 (IQR 42-148) hrs, p = 0.029) and significantly fewer patients required tracheostomy (20% vs. 9%, p = 0.040). The median ICU length of stay was 8 (IQR 4-12) days in the before phase and 6 (IQR 3-11) days in the after phase (p = 0.252). CONCLUSIONS: Implementing a sedation protocol that targeted light sedation and reduced benzodiazepine use led to significant improvements in the duration of mechanical ventilation and requirement for tracheostomy despite increases in the prevalence and duration of ICU delirium

The quasar M_bh - M_host relation through Cosmic Time II - Evidence for evolution from z=3 to the present age

We study the dependence of the M_bh - M_host relation on the redshift up to z=3 for a sample of 96 quasars the host galaxy luminosities of which are known. Black hole masses were estimated assuming virial equilibrium in the broad line regions (Paper I), while the host galaxy masses were inferred from their luminosities. With this data we are able to pin down the redshift dependence of the M_bh - M_host relation along 85 per cent of the Universe age. We show that, in the sampled redshift range, the M_bh - L_host relation remains nearly unchanged. Once we take into account the aging of the stellar population, we find that the M_bh / M_host ratio (Gamma) increases by a factor ~7 from z=0 to z=3. We show that Gamma evolves with z regardless of the radio loudness and of the quasar luminosity. We propose that most massive black holes, living their quasar phase at high-redshift, become extremely rare objects in host galaxies of similar mass in the Local Universe.Comment: 10 pages, 8 figures, 2 tables. Accepted for publication in MNRA

Elastin haploinsufficiency induces alternative aging processes in the aorta

Elastin, the main component of elastic fibers, is synthesized only in early life and provides the blood vessels with their elastic properties. With aging, elastin is progressively degraded, leading to arterial enlargement, stiffening, and dysfunction. Also, elastin is a key regulator of vascular smooth muscle cell proliferation and migration during development since heterozygous mutations in its gene (Eln) are responsible for a severe obstructive vascular disease, supravalvular aortic stenosis, isolated or associated to Williams syndrome. Here, we have studied whether early elastin synthesis could also influence the aging processes, by comparing the structure and function of ascending aorta from 6- and 24-month-old Eln+/- and Eln+/+ mice. Eln+/- animals have high blood pressure and arteries with smaller diameters and more rigid walls containing additional although thinner elastic lamellas. Nevertheless, longevity of these animals is unaffected. In young adult Eln+/- mice, some features resemble vascular aging of wild-type animals: cardiac hypertrophy, loss of elasticity of the arterial wall through enhanced fragmentation of the elastic fibers, and extracellular matrix accumulation in the aortic wall, in particular in the intima. In Eln+/- animals, we also observed an age-dependent alteration of endothelial vasorelaxant function. On the contrary, Eln+/- mice were protected from several classical consequences of aging visible in aged Eln+/+ mice, such as arterial wall thickening and alteration of alpha(1)-adrenoceptor-mediated vasoconstriction. Our results suggest that early elastin expression and organization modify arterial aging through their impact on both vascular cell physiology and structure and mechanics of blood vessels

Family stories, public silence: Irish identity construction amongst the second-generation Irish in England

Formal narratives of history, especially that of colonial oppression, have been central to the construction of national identities in Ireland. But the Irish diasporic community in Britain has been cut off from the reproduction of these narratives, most notably by their absence from the curriculum of Catholic schools, as result of the unofficial 'denationalisation' pact agreed by the Church in the 19th century (Hickman, 1995). The reproduction of Irish identities is largely a private matter, carried out within the home through family accounts of local connections, often reinforced by extended visits to parent/s 'home' areas. Recapturing a public dimension has often become a personal quest in adulthood, 'filling in the gaps'. This paper explores constructions of narratives of nation by a key diasporic population, those with one or two Irish-born parents. It places particular emphasis on varying regional/national contexts within which such constructions take place, drawing on focus group discussions and interviews for the ESRC-funded Irish 2 Project in five locations — London, Glasgow, Manchester, Coventry and Banbury

Colors of 2625 Quasars at 0<z<5 Measured in the Sloan Digital Sky Survey Photometric System

We present an empirical investigation of the colors of quasars in the Sloan Digital Sky Survey (SDSS) photometric system. The sample studied includes 2625 quasars with SDSS photometry. The quasars are distributed in a 2.5 degree wide stripe centered on the Celestial Equator covering $\sim529$ square degrees. Positions and SDSS magnitudes are given for the 898 quasars known prior to SDSS spectroscopic commissioning. New SDSS quasars represent an increase of over 200% in the number of known quasars in this area of the sky. The ensemble average of the observed colors of quasars in the SDSS passbands are well represented by a power-law continuum with $\alpha_{\nu} = -0.5$ ($f_{\nu} \propto \nu^{\alpha}$). However, the contributions of the $3000 {\rm \AA}$ bump and other strong emission lines have a significant effect upon the colors. The color-redshift relation exhibits considerable structure, which may be of use in determining photometric redshifts for quasars. The range of colors can be accounted for by a range in the optical spectral index with a distribution $\alpha_{\nu}=-0.5\pm0.65$ (95% confidence), but there is a red tail in the distribution. This tail may be a sign of internal reddening. Finally, we show that there is a continuum of properties between quasars and Seyfert galaxies and we test the validity of the traditional division between the two classes of AGN.Comment: 66 pages, 15 figures (3 color), accepted by A

Observations and Theoretical Implications of the Large Separation Lensed Quasar SDSS J1004+4112

We study the recently discovered gravitational lens SDSS J1004+4112, the first quasar lensed by a cluster of galaxies. It consists of four images with a maximum separation of 14.62''. The system has been confirmed as a lensed quasar at z=1.734 on the basis of deep imaging and spectroscopic follow-up observations. We present color-magnitude relations for galaxies near the lens plus spectroscopy of three central cluster members, which unambiguously confirm that a cluster at z=0.68 is responsible for the large image separation. We find a wide range of lens models consistent with the data, but they suggest four general conclusions: (1) the brightest cluster galaxy and the center of the cluster potential well appear to be offset by several kpc; (2) the cluster mass distribution must be elongated in the North--South direction, which is consistent with the observed distribution of cluster galaxies; (3) the inference of a large tidal shear (~0.2) suggests significant substructure in the cluster; and (4) enormous uncertainty in the predicted time delays between the images means that measuring the delays would greatly improve constraints on the models. We also compute the probability of such large separation lensing in the SDSS quasar sample, on the basis of the CDM model. The lack of large separation lenses in previous surveys and the discovery of one in SDSS together imply a mass fluctuation normalization \sigma_8=1.0^{+0.4}_{-0.2} (95% CL), if cluster dark matter halos have an inner slope -1.5. Shallower profiles would require higher values of \sigma_8. Although the statistical conclusion might be somewhat dependent on the degree of the complexity of the lens potential, the discovery is consistent with the predictions of the abundance of cluster-scale halos in the CDM scenario. (Abridged)Comment: 21 pages, 24 figures, 5 tables, accepted for publication in Ap