Decrease in total aneurysm-related deaths in the era of endovascular aneurysm repair

ObjectiveWith the expansion of elective abdominal aortic aneurysm (AAA) repair after the introduction of endovascular aneurysm repair (EVAR), there is a concern that even with a lower operative mortality there could be an increasing number of aneurysm-related deaths. To evaluate this, we looked at national trends in AAA repair volume as well as mortality rates after intact and ruptured AAA repair encompassing the introduction of EVAR.MethodsPatients with intact or ruptured AAA undergoing open repair or EVAR and all those with a diagnosis of ruptured AAA were identified within the 1993 to 2005 Nationwide Inpatient Sample database using International Classification of Diseases, 9th Revision, diagnosis and procedure codes. The number of repairs, number of rupture diagnoses without repair, number of deaths, and associated mortality rates were measured for each year of the database. Outcomes (mean annual volumes) were compared from the pre-EVAR era (1993 to 1998) with the post-EVAR era (2001 to 2005).ResultsSince its introduction, EVAR increased steadily and accounted for 56% of repairs yet only 27% of the deaths for intact repairs in 2005. The mean annual number of intact repairs increased from 36,122 in the pre-EVAR era to 38,901 in the post-EVAR era, whereas the mean annual number of deaths related to intact AAA repair decreased from 1693 pre-EVAR to 1207 post-EVAR (P < .0001). Mortality for all intact AAA repair decreased from 4.0% to 3.1% (P < .0001) pre-EVAR and post-EVAR, but open repair mortality was unchanged (open repair, 4.7% to 4.5%, P = .31; EVAR, 1.3%). During the same time, the mean annual number of ruptured repairs decreased from 2804 to 1846, and deaths from ruptured AAA repairs decreased from 2804 to 1846 (P < .0001). Mortality for ruptured AAA repair decreased from 44.3% to 39.9% (P < .0001) pre-EVAR and post-EVAR (open repair, 44.3% to 39.9%, P < .001; EVAR, 32.4%). The overall mean annual number of ruptured AAA diagnoses (9979 to 7773, P < .0001) and overall mean annual deaths from a ruptured AAA decreased post-EVAR (5338 to 3901, P < .0001).ConclusionSince the introduction of EVAR, the annual number of deaths from intact and ruptured AAA has significantly decreased. This coincided with an increase in intact AAA repair after the introduction of EVAR and a decrease in ruptured AAA diagnosis and repair volume

PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice

<p>Abstract</p> <p>Background</p> <p>Deficiency of the PERK eIF2α kinase in humans and mice results in postnatal exocrine pancreatic atrophy as well as severe growth and metabolic anomalies in other organs and tissues. To determine if the exocrine pancreatic atrophy is due to a cell-autonomous defect, the <it>Perk </it>gene was specifically ablated in acinar cells of the exocrine pancreas in mice.</p> <p>Results</p> <p>We show that expression of PERK in the acinar cells is required to maintain their viability but is not required for normal protein synthesis and secretion. Exocrine pancreatic atrophy in PERK-deficient mice was previously attributed to uncontrolled ER-stress followed by apoptotic cell death based on studies in cultured fibroblasts. However, we have found no evidence for perturbations in the endoplasmic reticulum or ER-stress and show that acinar cells succumb to a non-apoptotic form of cell death, oncosis, which is associated with a pronounced inflammatory response and induction of the pancreatitis stress response genes. We also show that mice carrying a knockout mutation of PERK's downstream target, ATF4, exhibit pancreatic deficiency caused by developmental defects and that mice ablated for ATF4's transcriptional target CHOP have a normal exocrine pancreas.</p> <p>Conclusion</p> <p>We conclude that PERK modulates secretory capacity of the exocrine pancreas by regulating cell viability of acinar cells.</p

PERK eIF2α kinase regulates neonatal growth by controlling the expression of circulating insulin-like growth factor-I derived from the liver

Humans afflicted with the Wolcott-Rallison syndrome and mice deficient for PERK (pancreatic endoplasmic reticulum eIF2α kinase) show severe postnatal growth retardation. In mice, growth retardation in Perk−/− mutants is manifested within the first few days of neonatal development. Growth parameters of Perk−/− mice, including comparison of body weight to length and organ weights, are consistent with proportional dwarfism. Tibia growth plates exhibited a reduction in proliferative and hypertrophic chondrocytes underlying the longitudinal growth retardation. Neonatal Perk−/− deficient mice show a 75% reduction in liver IGF-I mRNA and serum IGF-I within the first week, whereas the expression of IGF-I mRNA in most other tissues is normal. Injections of IGF-I partially reversed the growth retardation of the Perk−/− mice, whereas GH had no effect. Transgenic rescue of PERK activity in the insulin- secreting β-cells of the Perk−/− mice reversed the juvenile but not the neonatal growth retardation. We provide evidence that circulating IGF-I is derived from neonatal liver but is independent of GH at this stage. We propose that PERK is required to regulate the expression of IGF-I in the liver during the neonatal period, when IGF-I expression is GH-independent, and that the lack of this regulation results in severe neonatal growth retardation

Slow-Speed Supernovae from the Palomar Transient Factory: Two Channels

Since the discovery of the unusual prototype SN 2002cx, the eponymous class of low-velocity, hydrogen-poor supernovae has grown to include at most another two dozen members identified from several heterogeneous surveys, in some cases ambiguously. Here we present the results of a systematic study of 1077 hydrogen-poor supernovae discovered by the Palomar Transient Factory, leading to nine new members of this peculiar class. Moreover we find there are two distinct subclasses based on their spectroscopic, photometric, and host galaxy properties: The "SN 2002cx-like" supernovae tend to be in later-type or more irregular hosts, have more varied and generally dimmer luminosities, have longer rise times, and lack a Ti II trough when compared to the "SN 2002es-like" supernovae. None of our objects show helium, and we counter a previous claim of two such events. We also find that these transients comprise 5.6+17-3.7% (90% confidence) of all SNe Ia, lower compared to earlier estimates. Combining our objects with the literature sample, we propose that these subclasses have two distinct physical origins.Comment: 49 pages, 36 figures, submitted to Ap

Pigs in sequence space: A 0.66X coverage pig genome survey based on shotgun sequencing

BACKGROUND: Comparative whole genome analysis of Mammalia can benefit from the addition of more species. The pig is an obvious choice due to its economic and medical importance as well as its evolutionary position in the artiodactyls. RESULTS: We have generated ~3.84 million shotgun sequences (0.66X coverage) from the pig genome. The data are hereby released (NCBI Trace repository with center name "SDJVP", and project name "Sino-Danish Pig Genome Project") together with an initial evolutionary analysis. The non-repetitive fraction of the sequences was aligned to the UCSC human-mouse alignment and the resulting three-species alignments were annotated using the human genome annotation. Ultra-conserved elements and miRNAs were identified. The results show that for each of these types of orthologous data, pig is much closer to human than mouse is. Purifying selection has been more efficient in pig compared to human, but not as efficient as in mouse, and pig seems to have an isochore structure most similar to the structure in human. CONCLUSION: The addition of the pig to the set of species sequenced at low coverage adds to the understanding of selective pressures that have acted on the human genome by bisecting the evolutionary branch between human and mouse with the mouse branch being approximately 3 times as long as the human branch. Additionally, the joint alignment of the shot-gun sequences to the human-mouse alignment offers the investigator a rapid way to defining specific regions for analysis and resequencing

Inhibitory control, but not prolonged object-related experience appears to affect physical problem-solving performance of pet dogs

Human infants develop an understanding of their physical environment through playful interactions with objects. Similar processes may influence also the performance of non-human animals in physical problem-solving tasks, but to date there is little empirical data to evaluate this hypothesis. In addition or alternatively to prior experiences, inhibitory control has been suggested as a factor underlying the considerable individual differences in performance reported for many species. Here we report a study in which we manipulated the extent of object-related experience for a cohort of dogs (Canis familiaris) of the breed Border Collie over a period of 18 months, and assessed their level of inhibitory control, prior to testing them in a series of four physical problem-solving tasks. We found no evidence that differences in object-related experience explain variability in performance in these tasks. It thus appears that dogs do not transfer knowledge about physical rules from one physical problem-solving task to another, but rather approach each task as a novel problem. Our results, however, suggest that individual performance in these tasks is influenced in a complex way by the subject’s level of inhibitory control. Depending on the task, inhibitory control had a positive or a negative effect on performance and different aspects of inhibitory control turned out to be the best predictors of individual performance in the different tasks. Therefore, studying the interplay between inhibitory control and problem-solving performance will make an important contribution to our understanding of individual and species differences in physical problem-solving performance

PTF10iya: A short-lived, luminous flare from the nuclear region of a star-forming galaxy

We present the discovery and characterisation of PTF10iya, a short-lived (dt ~ 10 d, with an optical decay rate of ~ 0.3 mag per d), luminous (M_g ~ -21 mag) transient source found by the Palomar Transient Factory. The ultraviolet/optical spectral energy distribution is reasonably well fit by a blackbody with T ~ 1-2 x 10^4 K and peak bolometric luminosity L_BB ~ 1-5 x 10^44 erg per s (depending on the details of the extinction correction). A comparable amount of energy is radiated in the X-ray band that appears to result from a distinct physical process. The location of PTF10iya is consistent with the nucleus of a star-forming galaxy (z = 0.22405 +/- 0.00006) to within 350 mas (99.7 per cent confidence radius), or a projected distance of less than 1.2 kpc. At first glance, these properties appear reminiscent of the characteristic "big blue bump" seen in the near-ultraviolet spectra of many active galactic nuclei (AGNs). However, emission-line diagnostics of the host galaxy, along with a historical light curve extending back to 2007, show no evidence for AGN-like activity. We therefore consider whether the tidal disruption of a star by an otherwise quiescent supermassive black hole may account for our observations. Though with limited temporal information, PTF10iya appears broadly consistent with the predictions for the early "super-Eddington" phase of a solar-type star disrupted by a ~ 10^7 M_sun black hole. Regardless of the precise physical origin of the accreting material, the large luminosity and short duration suggest that otherwise quiescent galaxies can transition extremely rapidly to radiate near the Eddington limit; many such outbursts may have been missed by previous surveys lacking sufficient cadence.Comment: 18 pages, 8 figures; revised following referee's comment

The Two-Component Sensor Kinase TcsC and Its Role in Stress Resistance of the Human-Pathogenic Mold Aspergillus fumigatus

Two-component signaling systems are widespread in bacteria, but also found in fungi. In this study, we have characterized TcsC, the only Group III two-component sensor kinase of Aspergillus fumigatus. TcsC is required for growth under hyperosmotic stress, but dispensable for normal growth, sporulation and conidial viability. A characteristic feature of the ΔtcsC mutant is its resistance to certain fungicides, like fludioxonil. Both hyperosmotic stress and treatment with fludioxonil result in a TcsC-dependent phosphorylation of SakA, the final MAP kinase in the high osmolarity glycerol (HOG) pathway, confirming a role for TcsC in this signaling pathway. In wild type cells fludioxonil induces a TcsC-dependent swelling and a complete, but reversible block of growth and cytokinesis. Several types of stress, such as hypoxia, exposure to farnesol or elevated concentrations of certain divalent cations, trigger a differentiation in A. fumigatus toward a “fluffy” growth phenotype resulting in white, dome-shaped colonies. The ΔtcsC mutant is clearly more susceptible to these morphogenetic changes suggesting that TcsC normally antagonizes this process. Although TcsC plays a role in the adaptation of A. fumigatus to hypoxia, it seems to be dispensable for virulence

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal