Clinical Outcomes Following Stent Thrombosis Occurring In-Hospital Versus Out-of-Hospital Results From the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) Trial

ObjectivesThe study sought to determine whether rapid access to medical care and reperfusion results in a better prognosis in patients with in-hospital compared with out-of-hospital stent thrombosis (ST) in patients with ST-segment elevation myocardial infarction (STEMI) in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial.BackgroundWhether the prognosis of in-hospital and out-of-hospital ST are similar is uncertain, with conflicting data reported from prior studies.MethodsA total of 3,602 STEMI patients undergoing primary percutaneous coronary intervention (PCI) were randomized to bivalirudin (n = 1,800) versus unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) (UFH+GPI; n = 1,802). Stents were implanted in 3,202 patients, 156 (4.9%) of whom developed Academic Research Consortium definite/probable ST during 3-year follow-up. We investigated the 1-year clinical outcomes after ST in 54 patients with in-hospital ST compared with 102 patients with out-of-hospital ST.ResultsOne year after the ST event, patients with in-hospital compared with out-of-hospital ST had significantly greater mortality (27.8% vs. 10.8%, p < 0.01); most deaths in both groups occurred within 1 week of the ST event. Patients with in-hospital ST also had higher rates of major bleeding (21.2% vs. 6.0%, p < 0.01), but a lower rate of myocardial infarction (56.6% vs. 77.5%, p < 0.01). Subgroup analysis within both in-hospital and out-of-hospital ST groups indicated that subacute ST had the highest mortality. By multivariable analysis, 1-year mortality was significantly increased in patients with in-hospital compared with out-of-hospital ST (adjusted hazard ratio: 4.62, 95% confidence interval: 1.98 to 10.77, p < 0.01). Additional correlates of increased mortality after an ST event included diabetes and randomization to UFH+GPI (vs. bivalirudin).ConclusionsFollowing primary PCI for STEMI, more than one-third of all ST events during 3-year follow-up occurred during the index hospital phase. Mortality and major bleeding were significantly higher after in-hospital ST compared with out-of-hospital ST. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966

Low-density star cluster formation: Discovery of a young faint fuzzy on the outskirts of the low-mass spiral galaxy NGC 247

The classical globular clusters found in all galaxy types have half-light radii of rh ~2-4 pc, which have been tied to formation in the dense cores of giant molecular clouds. Some old star clusters have larger sizes, and it is unclear if these represent a fundamentally different mode of low-density star cluster formation. We report the discovery of a rare, young \u27faint fuzzy\u27 star cluster, NGC 247-SC1, on the outskirts of the low-mass spiral galaxy NGC 247 in the nearby Sculptor group, and measure its radial velocity using Keck spectroscopy. We use Hubble Space Telescope imaging to measure the cluster half-light radius of rh ≃ 12 pc and a luminosity of LV ≃ 4 × 105Lθ. We produce a colour-magnitude diagram of cluster stars and compare to theoretical isochrones, finding an age of ≃300 Myr, a metallicity of [Z/H] ~-0.6 and an inferred mass of M∗ ≃ 9 × 104Mθ. The narrow width of blue-loop star magnitudes implies an age spread of ≲50 Myr, while no old red-giant branch stars are found, so SC1 is consistent with hosting a single stellar population, modulo several unexplained bright \u27red straggler\u27 stars. SC1 appears to be surrounded by tidal debris, at the end of an ∼2 kpc long stellar filament that also hosts two low-mass, low-density clusters of a similar age. We explore a link between the formation of these unusual clusters and an external perturbation of their host galaxy, illuminating a possible channel by which some clusters are born with large sizes

Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.</p

Estimating Grizzly and Black Bear Population Abundance and Trend in Banff National Park Using Noninvasive Genetic Sampling

We evaluated the potential of two noninvasive genetic sampling methods, hair traps and bear rub surveys, to estimate population abundance and trend of grizzly (Ursus arctos) and black bear (U. americanus) populations in Banff National Park, Alberta, Canada. Using Huggins closed population mark-recapture models, we obtained the first precise abundance estimates for grizzly bears ( = 73.5, 95% CI = 64–94 in 2006;  = 50.4, 95% CI = 49–59 in 2008) and black bears ( = 62.6, 95% CI = 51–89 in 2006;  = 81.8, 95% CI = 72–102 in 2008) in the Bow Valley. Hair traps had high detection rates for female grizzlies, and male and female black bears, but extremely low detection rates for male grizzlies. Conversely, bear rubs had high detection rates for male and female grizzlies, but low rates for black bears. We estimated realized population growth rates, lambda, for grizzly bear males ( = 0.93, 95% CI = 0.74–1.17) and females ( = 0.90, 95% CI = 0.67–1.20) using Pradel open population models with three years of bear rub data. Lambda estimates are supported by abundance estimates from combined hair trap/bear rub closed population models and are consistent with a system that is likely driven by high levels of human-caused mortality. Our results suggest that bear rub surveys would provide an efficient and powerful means to inventory and monitor grizzly bear populations in the Central Canadian Rocky Mountains

PI 3 Kinase Related Kinases-Independent Proteolysis of BRCA1 Regulates Rad51 Recruitment during Genotoxic Stress in Human Cells

The function of BRCA1 in response to ionizing radiation, which directly generates DNA double strand breaks, has been extensively characterized. However previous investigations have produced conflicting data on mutagens that initially induce other classes of DNA adducts. Because of the fundamental and clinical importance of understanding BRCA1 function, we sought to rigorously evaluate the role of this tumor suppressor in response to diverse forms of genotoxic stress.We investigated BRCA1 stability and localization in various human cells treated with model mutagens that trigger different DNA damage signaling pathways. We established that, unlike ionizing radiation, either UVC or methylmethanesulfonate (MMS) (generating bulky DNA adducts or alkylated bases respectively) induces a transient downregulation of BRCA1 protein which is neither prevented nor enhanced by inhibition of PIKKs. Moreover, we found that the proteasome mediates early degradation of BRCA1, BARD1, BACH1, and Rad52 implying that critical components of the homologous recombination machinery need to be functionally abrogated as part of the early response to UV or MMS. Significantly, we found that inhibition of BRCA1/BARD1 downregulation is accompanied by the unscheduled recruitment of both proteins to chromatin along with Rad51. Consistently, treatment of cells with MMS engendered complete disassembly of Rad51 from pre-formed ionizing radiation-induced foci. Following the initial phase of BRCA1/BARD1 downregulation, we found that the recovery of these proteins in foci coincides with the formation of RPA and Rad51 foci. This indicates that homologous recombination is reactivated at later stage of the cellular response to MMS, most likely to repair DSBs generated by replication blocks.Taken together our results demonstrate that (i) the stabilities of BRCA1/BARD1 complexes are regulated in a mutagen-specific manner, and (ii) indicate the existence of mechanisms that may be required to prevent the simultaneous recruitment of conflicting signaling pathways to sites of DNA damage

Physiological Correlates of Volunteering

We review research on physiological correlates of volunteering, a neglected but promising research field. Some of these correlates seem to be causal factors influencing volunteering. Volunteers tend to have better physical health, both self-reported and expert-assessed, better mental health, and perform better on cognitive tasks. Research thus far has rarely examined neurological, neurochemical, hormonal, and genetic correlates of volunteering to any significant extent, especially controlling for other factors as potential confounds. Evolutionary theory and behavioral genetic research suggest the importance of such physiological factors in humans. Basically, many aspects of social relationships and social activities have effects on health (e.g., Newman and Roberts 2013; Uchino 2004), as the widely used biopsychosocial (BPS) model suggests (Institute of Medicine 2001). Studies of formal volunteering (FV), charitable giving, and altruistic behavior suggest that physiological characteristics are related to volunteering, including specific genes (such as oxytocin receptor [OXTR] genes, Arginine vasopressin receptor [AVPR] genes, dopamine D4 receptor [DRD4] genes, and 5-HTTLPR). We recommend that future research on physiological factors be extended to non-Western populations, focusing specifically on volunteering, and differentiating between different forms and types of volunteering and civic participation

Near-perfect broadband absorption from hyperbolic metamaterial nanoparticles

Broadband absorbers are essential components of many light detection, energy harvesting, and camouflage schemes. Current designs are either bulky or use planar films that cause problems in cracking and delamination during flexing or heating. In addition, transferring planar materials to flexible, thin, or low-cost substrates poses a significant challenge. On the other hand, particle-based materials are highly flexible and can be transferred and assembled onto a more desirable substrate but have not shown high performance as an absorber in a standalone system. Here, we introduce a class of particle absorbers called transferable hyperbolic metamaterial particles (THMMP) that display selective, omnidirectional, tunable, broadband absorption when closely packed. This is demonstrated with vertically aligned hyperbolic nanotube (HNT) arrays composed of alternating layers of aluminum-doped zinc oxide and zinc oxide. The broadband absorption measures >87% from 1,200 nm to over 2,200 nm with a maximum absorption of 98.1% at 1,550 nm and remains large for high angles. Furthermore, we show the advantages of particle-based absorbers by transferring the HNTs to a polymer substrate that shows excellent mechanical flexibility and visible transparency while maintaining near-perfect absorption in the telecommunications region. In addition, other material systems and geometries are proposed for a wider range of applications