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Background: Cerebral vasospasm is a leading cause of neurological disability following aneurysmal subarachnoid hemorrhage (aSAH). Clinical features associated with vasospasm development include blood burden on CT, neurological status, age and aneurysm location. Early cerebral CT perfusion (CTP) scanning in aSAH may be an independent predictor of vasospasm and/or delayed cerebral ischemia (DCI). Methods: Forty-one patients with aSAH were prospectively enrolled. Baseline data collected included WFNS grade, loss of consciousness at ictus, and modified Fisher grade. CTP was obtained at baseline and on day 6 post SAH. Cerebral blood volume, cerebral blood flow and mean transit time were measured. DCI was confirmed by a combination of clinical assessments, non-contrast CT and CTP. Radiological vasospasm was assessed with CT angiography. Results: Despite 80% of patients having a modified Fisher grade 3 or 4 aSAH, one-third presenting with ictal LOC and half having anterior communicating artery aneurysms, only one patient developed clinical evidence of vasospasm/DCI. Two others had asymptomatic radiological vasospasm. CTP parameters did not differ between groups defined by clinical predictors. Conclusions: In an unexpected finding, clinical and radiological vasospasm were very uncommon in this cohort. Clinical predictive variables correlated poorly with development of vasospasm. CTP may help refine the model but further work is needed.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
We present a conditional space–time proper orthogonal decomposition (POD) formulation that is tailored to the eduction of the average, rare or intermittent events from an ensemble of realizations of a fluid process. By construction, the resulting spatio-temporal modes are coherent in space and over a predefined finite time horizon, and optimally capture the variance, or energy of the ensemble. For the example of intermittent acoustic radiation from a turbulent jet, we introduce a conditional expectation operator that focuses on the loudest events, as measured by a pressure probe in the far field and contained in the tail of the pressure signal’s probability distribution. Applied to high-fidelity simulation data, the method identifies a statistically significant ‘prototype’, or average acoustic burst event that is tracked over time. Most notably, the burst event can be traced back to its precursor, which opens up the possibility of prediction of an imminent burst. We furthermore investigate the mechanism underlying the prototypical burst event using linear stability theory and find that its structure and evolution are accurately predicted by optimal transient growth theory. The jet-noise problem demonstrates that the conditional space–time POD formulation applies even for systems with probability distributions that are not heavy-tailed, i.e. for systems in which events overlap and occur in rapid succession.
Although shyness is a ubiquitous phenomenon with early developmental origins, little research has examined the influence of prenatal exposures on the developmental trajectory of shyness. Here, we examined trajectories of shyness from childhood to adulthood in three groups (N = 254), with varying degrees of prenatal adversity as indicated by the number of stressful exposures: extremely low birth weight (ELBW; <1000 g) survivors prenatally exposed to exogenous corticosteroids (ELBW+S, n = 56); ELBW survivors not prenatally exposed to exogenous corticosteroids (ELBW+NS, n = 56); and normal birth weight (NBW, n = 142) controls. Multilevel modeling revealed that the ELBW+S individuals exhibited the highest levels of childhood shyness, which remained stable into adulthood. The ELBW+NS and NBW controls had comparably low levels of childhood shyness; however, the ELBW+NS individuals experienced patterns of increasing shyness, while NBW controls displayed decreases in shyness into adulthood. We speculate that individuals exposed to multiple prenatal stressors (i.e., ELBW+S) may be developmentally programmed to be more sensitive to detecting social threat, with one manifestation being early developing, stable shyness, while increasing shyness among ELBW+NS individuals may reflect a later developing shyness influenced by postnatal context. We discuss the implications of these findings for understanding the developmental origins and developmental course of human shyness from childhood through adulthood.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Although sorghum [Sorghum bicolor (L.) Moench ssp. bicolor] is the fifth most important grain crop in terms of global production, no commercial hybrids carry genetically engineered (GE) traits for resistance to insect pests or herbicides due to regulatory concerns about gene flow to weedy relatives. However, non-GE herbicide resistance currently is being developed in grain sorghum and will likely transfer to related weeds. Monitoring the impact of this new nuclear technology on the evolution and invasiveness of related weeds requires a baseline understanding of the population biology of grain sorghum genes once they transfer to in situ weed populations. We previously characterized the rate of gene flow from grain sorghum to shattercane [Sorghum bicolor (L.) Moench nothosubsp. drummondii (Steud.) de Wet ex. Davidse], a conspecific weed relatively common in North America; as well as the ecological fitness of an F1 population when S. bicolor nothosubsp. drummondii was the maternal parent. Here we report the ecological fitness of a S. bicolor nothosubsp. drummondii × S. bicolor ssp. bicolor F2 population relative to its crop and weed parents. Parental and F2 populations were grown in two Nebraska environments in 2012 and 2013. Traits evaluated included overwinter survival, field emergence, biomass production and partitioning at anthesis, total seed production, and 100-seed weight. Results indicated that F2 traits were generally intermediate between the parents, but more similar to S. bicolor nothosubsp. drummondii than to grain sorghum. The one exception was overwinter survival, which was nearly 0% for both the F2 and the grain sorghum parent in these northern environments. Thus, the frequency of crop alleles stably introgressed into S. bicolor nothosubsp. drummondii populations appears to primarily depend on overwinter survival of the F2 and which selective pressures are imposed upon it by the cropping system. These data provide needed baseline information about the environmental fate of nuclear genetic technologies deployed in this important global crop.
We present the first data release of the SkyMapper Southern Survey, a hemispheric survey carried out with the SkyMapper Telescope at Siding Spring Observatory in Australia. Here, we present the survey strategy, data processing, catalogue construction, and database schema. The first data release dataset includes over 66 000 images from the Shallow Survey component, covering an area of 17 200 deg2 in all six SkyMapper passbands uvgriz, while the full area covered by any passband exceeds 20 000 deg2. The catalogues contain over 285 million unique astrophysical objects, complete to roughly 18 mag in all bands. We compare our griz point-source photometry with Pan-STARRS1 first data release and note an RMS scatter of 2%. The internal reproducibility of SkyMapper photometry is on the order of 1%. Astrometric precision is better than 0.2 arcsec based on comparison with Gaia first data release. We describe the end-user database, through which data are presented to the world community, and provide some illustrative science queries.
We analyse unsteady cavity dynamics, cavitation patterns and instability mechanisms governing partial cavitation in the flow past a sharp convergent–divergent wedge. Reproducing a recent reference experiment by numerical simulation, the investigated flow regime is characterised by large-scale cloud cavitation. In agreement with the experiments, we find that cloud shedding is dominated by the periodic occurrence of condensation shocks, propagating through the two-phase medium. The physical model is based on the homogeneous mixture approach, the assumption of thermodynamic equilibrium, and a closed-form barotropic equation of state. Compressibility of water and water vapour is taken into account. We deliberately suppress effects of molecular viscosity, in order to demonstrate that inertial effects dominate the flow evolution. We qualify the flow predictions, and validate the numerical approach by comparison with experiments. In agreement with the experiments, the vapour volume fraction within the partial cavity reaches values
for its spanwise average. Very good agreement is further obtained for the shedding Strouhal number, the cavity growth and collapse velocities, and for typical coherent flow structures. In accordance with the experiments, the simulations reproduce a condensation shock forming at the trailing part of the partial cavity. It is demonstrated that it satisfies locally Rankine–Hugoniot jump relations. Estimation of the shock propagation Mach number shows that the flow is supersonic. With a magnitude of only a few kPa, the pressure rise across the shock is much lower than for typical cavity collapse events. It is thus far too weak to cause cavitation erosion directly. However, by affecting the dynamics of the cavity, the flow aggressiveness can be significantly altered. Our results indicate that, in addition to classically observed re-entrant jets, condensation shocks feed an intrinsic instability mechanism of partial cavitation.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Perinatal and later postnatal adversities have been shown to adversely affect socioeconomic trajectories, while enhanced early cognitive abilities improve them. However, little is known about the combined influence of these exposures on social mobility. In this study, we examined if childhood IQ moderated the association between four different types of postnatal adversity (childhood socioeconomic disadvantage, childhood sexual abuse, lifetime psychiatric disorder, and trait neuroticism) and annual earnings at 30–35 years of age in a sample of 88 extremely low birth weight survivors. Our results suggested that higher childhood IQ was associated with greater personal income at age 30–35. Extremely low birth weight survivors who did not face psychological adversities and who had higher childhood IQ reported higher income in adulthood. However, those who faced psychological adversity and had higher childhood IQ generally reported lower income in adulthood. Our findings suggest that cognitive reserve may not protect preterm survivors against the complex web of risk factors affecting their later socioeconomic attainment.
Detailed measurements of crystal outlines and fabrics have been performed on 35 000 crystals in fifteen 10 × 20 cm2 vertical thin sections from the North Greenland Icecore Project (NorthGRIP) ice core, evenly distributed in the depth interval 115–880m. The crystals exhibit important changes over this period. As the ice gets older the mean crystal area increases towards a constant value, the shape of the crystals becomes increasingly irregular, and the area distribution of crystals develops from a single log-normal distribution into a bimodal lognormal distribution. The c-axis fabric of the ice shows a smooth development of an increasingly stronger vertical fabric with depth, and the formation of a weak vertical girdle. Already in the younger samples the fabric is rather strongly oriented towards vertical. The fabric and the area of individual crystals are found not to correlate. A simple model, which takes into account the vertical strain of the ice, is applied in an attempt to determine the crystal growth rate at NorthGRIP.
OBJECTIVES/SPECIFIC AIMS: Obstructive lung disease following particulate matter (PM) exposure is a major health concern. Coexisting metabolic syndrome (MetSyn) often occurs. Receptor for advanced glycation end products (RAGE) is highly expressed in the lung, is a strong predictor of FEV1, and is a key mediator of MetSyn. To determine if the loss of RAGE protects from the persistence of effects of particulate associated lung injury in a murine model. METHODS/STUDY POPULATION: Wild type (WT) and RAGE knockout (RKO) mice were exposed to 100 μg of PM (WTC-Aggregate, PM53) or PBS control by oropharyngeal aspiration. Lung function, methacholine challenge, and bronchoalveolar lavage (BAL) were quantified 28 days after PM exposure using flexiVent (Scireq Montreal, QC). BAL was obtained and cell differentials, cytokines and transcription factors were assayed. Bio-volume to airspace ratio and mean chord length were measured (Image J and Adobe Photoshop). RESULTS/ANTICIPATED RESULTS: WT mice were hyper-reactive to methacholine compared with their PBS controls 28 days after a single exposure to PM. They recovered from increased neutrophilia, loss of FEV, decreased compliance, and increased resistance, which were previously observed 24-hours after exposure. RKO were not hyper-reactive when compared with their own PBS controls. Lung histology shows persistence of loss of alveolar space in WT mice exposed to PM after 28 days. Area fraction was significantly higher in PM exposed WT mice after 28 days which was not significant after 24 hours. Mean chord length was significantly shorter for PM exposed at both time points for WT mice. The relative expression of phosphorylated to total CREB and ERK1/2 proteins was lower in RKO PM exposed mice compared with WT PM while STAT3 expression was lower in WT PM compared with WT PBS. PM induced a lower fold change of total proteins from the PBS controls in RKO for CREB, p38, ERK1/2, STAT3, and STAT5. JNK and p70S6k total proteins expressed a decreased fold change in WT PM exposed mice compared with WT PBS controls. DISCUSSION/SIGNIFICANCE OF IMPACT: A single dose of PM can produce persistent airway hyper-reactivity after 28 days of exposure. This PM induced injury is alleviated in the absence of RAGE, similar to what was seen at 24 hours. Inhibiting RAGE may be key to limiting the persistent inflammatory effects of high intensity PM exposure.
The discussions about stellar populations and their spatial distribution can be best advanced by studies of special and well defined star types. The study of subdwarf B stars provides great promise: it is relatively easy both to find sdB stars and to determine their physical parameters.
Sublimation (vaporization) of the icy component of a cometary nucleus determines the initial composition of the coma gas as it streams outward and escapes. Photolytic reactions in the inner coma, escape of fast, light species such as atomic and molecular hydrogen, and solar wind interaction in the outer coma alter the chemical composition and the physical nature of the coma gas. Models that describe these interactions must include (1) chemical kinetics, (2) coma energy balance, (3) multifluid flow for the rapidly escaping light components, the heavier bulk fluid, and the plasma with separate temperatures for electrons and the remainder of the gas, (4) transition from a collision dominated inner region to free molecular flow of neutrals in the outer region, (5) pickup of cometary ions by the solar wind, (6) counter and cross streaming of neutrals with respect to the plasma which outside of the contact surface also contains solar wind ions, and (7) magnetic fields carried by the solar wind. Progress on such models is described and results including velocity, temperature, and number density profiles for important chemical species are presented and compared with observations.
We sought to comprehensively assess the prevalence and outcomes of complications associated with Staphylococcus aureus bacteremia (SAB) in children. Secondarily, prevalence of methicillin resistance and outcomes of complications from methicillin-resistant S. aureus (MRSA) vs. methicillin-susceptible S. aureus SAB were assessed. This is a single-center cross-sectional study of 376 patients ⩽18 years old with SAB in 1990–2014. Overall, 197 (52%) patients experienced complications, the most common being osteomyelitis (33%), skin and soft tissue infection (31%), and pneumonia (25%). Patients with complications were older (median 3 vs. 0·7 years, P = 0·05) and more had community-associated SAB (66% vs. 34%, P = 0·001). Fewer patients with complications had a SAB-related emergency department or hospital readmission (10% vs. 19%, P = 0·014). Prevalence of methicillin resistance increased from 1990–1999 to 2000–2009, but decreased in 2010–2014. Complicated MRSA bacteremia resulted in more intensive care unit admissions (66% vs. 47%, P = 0·03) and led to increased likelihood of having ⩾2 foci (58% vs. 26%, P < 0·001). From multivariate analysis, community-associated SAB increased risk and concurrent infections decreased risk of complications (odds ratio (OR) 1·82 (1·1–3·02), P = 0·021) and (OR 0·58 (0·34–0·97), P = 0·038), respectively. In conclusion, children with SAB should be carefully evaluated for complications. Methicillin resistance remains associated with poor outcomes but have decreased in overall prevalence.