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Here we present the synthesis of porous platinum–palladium macrobeams templated from high aspect ratio Magnus’ salt needle derivatives. The combination of [PtCl4]2− and/or [PdCl4]2− with [Pt(NH3)4]2+ ions results in salt needles ranging from 15 to 300 µm in length. Electrochemical reduction of the salt templates results in porous macrobeams with a square cross-section. Porous side wall texture and elemental composition was controlled with initial platinum to palladium salt ratio. Macrobeam free-standing films exhibited a specific capacitance up to 11.73 F/g and a solvent accessible surface area of 26.6 m2/g. These salt-templated porous platinum–palladium macrobeams offer a promising material for fuel cell catalysis.
OBJECTIVES/SPECIFIC AIMS: The morbidity and mortality in adults with single ventricular hearts who have undergone Fontan palliation is poorly defined. These patients have a high burden of arrhythmia, heart failure, and re-operation. We hypothesized that age and type of Fontan predict occurrence of arrhythmia. METHODS/STUDY POPULATION: In total, 205 patients aged 18 years who had undergone a Fontan procedure were identified. Those with incomplete data were excluded. Demographic, anatomic, pharmacologic, imaging, hemodynamic, and electrophysiologic data were collected. The χ2 and Mann-Whitney U tests were used to test significance defined as p<0.05. RESULTS/ANTICIPATED RESULTS: Of the 205 patients identified, 59 had been lost to follow-up. Of the 146 patients (77, 53% female) actively followed 18 (12%) had died at a median (IQR) age of 27 (21–34.3); in patients alive as of 10/2016 the median age was 26 years (22–34). Fontan types were lateral tunnel (LT) (n=79, 54.1%), extracardiac (EC) (n=32, 22%), right atrial to pulmonary artery (RV-PA) (n=28, 19%), and Fontan with Bjork modification (n=4, 2.7%). Systemic left ventricle (n=96, 66%) was more common than systemic right ventricle (n=43, 30%). Of the 146 patients, 101 (69%) had significant morbidity or mortality: 86 (59%) were diagnosed with arrhythmia, 18 (12%) died, and 11 (8%) underwent heart transplants. Frequent procedures included: Fontan revisions/cryoablation in 28 (19%), electrophysiology studies with ablation in 73 (50%), and pacemakers in 53 (36%). Of the arrhythmia diagnoses, 57 (64%) were atrial tachyarrhythmias. RV-PA Fontan procedures were associated with significantly more atrial arrhythmia than all other Fontan types (70% vs. 30%; p<0.01). There was no statistical difference in occurrence of atrial arrhythmia in adults with LT Versus EC Fontans (p=0.3). While patients who had undergone RV-PA and Bjork Fontans were older with median age 34 years, there was no significant difference in age between LT and EC (median 24.0 and 24.5). DISCUSSION/SIGNIFICANCE OF IMPACT: Adult survivors of the Fontan procedure suffer from significant morbidity and mortality. The single most prevalent morbidity is atrial arrhythmia. We conclude that RV-PA Fontans, now obsolete, have the highest prevalence of arrhythmia and that there is no difference in arrhythmia burden between LT and EC Fontans. Given the high prevalence of morbidity and mortality in this population, it is imperative that they be followed by cardiologists with expertise in congenital heart disease.
The aim of this study was to describe previously unrecognised or under-recognised adverse events associated with Melody® valve implantation.
In rare diseases and conditions, it is typically not feasible to conduct large-scale safety trials before drug or device approval. Therefore, post-market surveillance mechanisms are necessary to detect rare but potentially serious adverse events.
We reviewed the United States Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database and conducted a structured literature review to evaluate adverse events associated with on- and off-label Melody® valve implantation. Adverse events were compared with those described in the prospective Investigational Device Exemption and Post-Market Approval Melody® transcatheter pulmonary valve trials.
We identified 631 adverse events associated with “on-label” Melody® valve implants and 84 adverse events associated with “off-label” implants. The most frequent “on-label” adverse events were similar to those described in the prospective trials including stent fracture (n=210) and endocarditis (n=104). Previously unrecognised or under-recognised adverse events included stent fragment embolisation (n=5), device erosion (n=4), immediate post-implant severe valvar insufficiency (n=2), and late coronary compression (n=2 cases at 5 days and 3 months after implantation). Under-recognised adverse events associated with off-label implantation included early valve failure due to insufficiency when implanted in the tricuspid position (n=7) and embolisation with percutaneous implantation in the mitral position (n=5).
Post-market passive surveillance does not demonstrate a high frequency of previously unrecognised serious adverse events with “on-label” Melody® valve implantation. Further study is needed to evaluate safety of “off-label” uses.
Recurrent GBM and AA have a dismal prognosis and a high unmet need for effective therapies. Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that encodes the transgene cytosine deaminase (CD). Toca 511 selectively infects, persists and spreads in tumor. Subsequent oral administration of 5-fluorocytosine (Toca FC) produces 5-fluorouracil (5-FU) by CD within infected cells. 5-FU kills cancer cells and myeloid derived suppressor cells, inducing robust antitumor immune responses in animal models. Clinical data from phase 1 trials are consistent with this mechanism of action, and show extended survival compared to historical controls. Toca 5 is a multicenter, randomized, open-label Phase 2/3 trial of Toca 511 and Toca FC versus standard of care administered to patients undergoing resection for first or second recurrence of GBM or AA. Phase 2 will enroll 170 patients. Primary endpoint is overall survival (OS). Key secondary endpoints are safety, objective response rate, clinical benefit rate, progression-free survival, and landmark OS. Key inclusion criteria are age 18-75 years, histologically proven GBM or AA, measurable disease preoperatively of less than 5cm, candidate for equal or greater 80% resection of enhancing tumor based on pre-operative evaluation, and KPS equal or greater to 70. Assays for immune monitoring will be performed and molecular profiling of resected tumor samples will be correlated efficacy.
Recurrent glioblastoma (GBM) has an unmet need for effective therapies. Toca 511 (vocimagene amiretrorepvec), a retroviral replicating vector with the transgene cytosine deaminase, selectively infects, persists and spreads in tumor. Subsequent oral administration of 5-fluorocytosine (Toca FC) produces 5-fluorouracil (5-FU) within infected cells. 5-FU kills cancer cells and myeloid derived suppressor cells, inducing robust antitumor immune responses in animal models. In 2 Phase 1 studies, Toca 511 was administered into the cavity wall after surgical resection (NCT01470794) or intratumoral injection by biopsy needle (NCT01156584). To provide context to the results observed, subjects were compared to an external lomustine treated control (Courtesy Denovo Biopharma; Wick 2010). Treatment with Toca 511/Toca FC from 2 Phase I studies showed significant improvement in OS HR equals to 0.48, p less than 0.001, with similar effect in the surgical resection (OS HR 0.45, p equals to 0.003) and intratumoral injection (OS HR 0.56, p equals to 0.060). Fewer related greater or equal to Grade 3 adverse events (AEs) were reported for Toca 511/Toca FC (2.5 percent) vs. lomustine (36.9 percent). There was a virtual absence of hematologic toxicity for Toca 511/Toca FC vs. lomustine (Grade greater or equal to 3 thrombocytopenia 23.8 percent). Discontinuations for AEs occurred in 0percent for Toca 511/Toca FC vs. 4.8 percent for lomustine. Toca 511 is surgically delivered and treatment-emergent AEs regardless of attribution included incision site pain (20 percent), procedural pain (12.5 percent), and wound infection (5 percent) vs. 0percent, 1.2 percent, 1.2 percent respectively for lomustine. Toca 511/Toca FC significantly improved survival and safety relative to lomustine. A Phase 2/3 trial has launched (NCT02414165).
The aim of the study was to evaluate the trends in respiratory syncytial virus-related hospitalisations and associated outcomes in children with haemodynamically significant heart disease in the United States of America.
The Kids’ Inpatient Databases (1997–2012) were used to estimate the incidence of respiratory syncytial virus hospitalisation among children ⩽24 months with or without haemodynamically significant heart disease. Weighted multivariable logistic regression and chi-square tests were used to evaluate the trends over time and factors associated with hospitalisation, comparing eras before and after publication of the 2003 American Academy of Pediatrics palivizumab immunoprophylaxis guidelines. Secondary outcomes included in-hospital mortality, morbidity, length of stay, and cost.
Overall, 549,265 respiratory syncytial virus-related hospitalisations were evaluated, including 2518 (0.5%) in children with haemodynamically significant heart disease. The incidence of respiratory syncytial virus hospitalisation in children with haemodynamically significant heart disease decreased by 36% when comparing pre- and post-palivizumab guideline eras versus an 8% decline in children without haemodynamically significant heart disease (p<0.001). Children with haemodynamically significant heart disease had higher rates of respiratory syncytial virus-associated mortality (4.9 versus 0.1%, p<0.001) and morbidity (31.5 versus 3.5%, p<0.001) and longer hospital length of stay (17.9 versus 3.9 days, p<0.001) compared with children without haemodynamically significant heart disease. The mean cost of respiratory syncytial virus hospitalisation in 2009 was $58,166 (95% CI:$46,017, $70,315).
These data provide stakeholders with a means to evaluate the cost–utility of various immunoprophylaxis strategies.
Cosmology is one of the most dynamically evolving areas of astrophysics today. Twenty years ago the estimates of the amplitude of the primordial fluctuations were about 10-3, almost a factor of 100 off of today’s measurements. Ten years ago we could only hope for high precision measurements of large scale structure, there were less than 5000 redshifts measured, and only a handful of normal galaxies with z > 1 were known. Computer models of structure formation had just begun to consider non-power-law spectra based on physical models like hot/cold dark matter. As a consequence there was considerable freedom in adjusting parameters in the various galaxy formation scenarios. In contrast, many of today’s debates are about factors of 2 and soon we will be arguing about 10% differences. The Harrison-Zeldovich shape of the primordial fluctuation spectrum, first derived from philosophical arguments can now be quantified from detections of fluctuations by COBE. The number of available redshifts is beyond 50,000, and soon we will have redshift surveys surpassing 1 million galaxies. N-body simulations are becoming more sophisticated, of higher resolution, and incorporating complex gas dynamics.
We estimated the prevalence of food insecurity among people who inject drugs (PWID) in Los Angeles and San Francisco and explored correlates of food insecurity.
A cross-sectional study that measured 30 d food insecurity using the US Adult Food Security Survey ten-item Module developed by the US Department of Agriculture. Food insecurity was defined as including low and very low food security.
Two cities in the state of California, USA.
Male and female active PWID (n 777).
Among participants, 58 % reported food insecurity and 41 % reported very low food security. Food-insecure PWID were more likely to report being homeless (prevalence ratio (PR)=1·20; 95 % CI 1·05, 1·37), chest pain in the past 12 months (PR=1·19; CI 1·06, 1·35), acquiring syringes from someone who goes to a syringe exchange programme (PR=1·27; 95 % CI 1·13, 1·43) and feeling at risk for arrest for possession of drug paraphernalia (PR=1·30; 95 % CI 1·15, 1·46).
Current food insecurity was common among PWID in these two cities, yet few factors were independently associated with food insecurity. These data suggest that broad strategies to improve food access for this high-risk population are urgently needed.
A new device-first low-temperature bonded gallium nitride (GaN)-on-diamond
high-electronic mobility transistor (HEMT) technology with state-of-the-art,
radio frequency (RF) power performance is described. In this process, the
devices were first fabricated on a GaN-on-silicon carbide (SiC) epitaxial wafer
and were subsequently separated from the SiC and bonded onto a
high-thermal-conductivity diamond substrate. Thermal measurements showed that
the GaN-on-diamond devices maintained equivalent or lower junction temperatures
than their GaN-on-SiC counterparts while delivering more than three-times higher
RF power within the same active area. Such results demonstrate that the GaN
device transfer process is capable of preserving intrinsic transistor electrical
performance while taking advantage of the excellent thermal properties of
diamond substrates. Preliminary step-stress and room-temperature, steady-state
life testing shows that the low-temperature bonded GaN-on-diamond device has no
inherently reliability limiting factor. GaN-on-diamond is ideally suited to
wideband electronic warfare (EW) power amplifiers as they are the most thermally
challenging due to continuous wave (CW) operation and the reduced power-added
efficiency obtained with ultra-wide bandwidth circuit implementations.
Phenol, also known as carbolic acid or phenic acid, is a priority pollutant in aquatic ecosystems. The present study has investigated metabolic activities and transcription profiles of cytochrome P450 enzymes in Chironomus kiinensis under phenol stress. Exposure of C. kiinensis larvae to three sublethal doses of phenol (1, 10 and 100 µM) inhibited cytochrome P450 enzyme activity during the 96 h exposure period. The P450 activity measured after the 24 h exposure to phenol stress could be used to assess the level (low or high) of phenol contamination in the environment. To investigate the potential of cytochrome P450 genes as molecular biomarkers to monitor phenol contamination, the cDNA of ten CYP6 genes from the transcriptome of C. kiinensis were identified and sequenced. The open reading frames of the CYP6 genes ranged from 1266 to 1587 bp, encoding deduced polypeptides composed of between 421 and 528 amino acids, with predicted molecular masses from 49.01 to 61.94 kDa and isoelectric points (PI) from 6.01 to 8.89. Among the CYP6 genes, the mRNA expression levels of the CYP6EW3, CYP6EV9, CYP6FV1 and CYP6FV2 genes significantly altered in response to phenol exposure; therefore, these genes could potentially serve as biomarkers in the environment. This study shows that P450 activity combined with one or multiple CYP6 genes could be used to monitor phenol pollution.
This study examined the temporal and spatial patterns of diarrhoea in relation to hydro-meteorological factors in the Mekong Delta area in Vietnam. A time-series design was applied to examine the temporal pattern of the climate–diarrhoea relationship using Poisson regression models. Spatial analysis was applied to examine the spatial clusters of diarrhoea using Global Moran's I and local indicators of spatial autocorrelation (LISA). The temporal pattern showed that the highest peak of diarrhoea was from weeks 30–42 corresponding to August–October annually. A 1 cm increase in river water level at a lag of 1 week was associated with a small [0·07%, 95% confidence interval (CI) 0·01–0·1] increase in the diarrhoeal rate. A 1 °C increase in temperature at lag of 2 and 4 weeks was associated with a 1·5% (95% CI 0·3−2·7) and 1·1% (95% CI 0·1−2·3) increase in diarrhoeal risk, respectively. Relative humidity and diarrhoeal risk were in nonlinear relationship. The spatial analysis showed significant clustering of diarrhoea, and the LISA map shows three multi-centred diarrhoeal clusters and three single-centred clusters in the research location. The findings suggest that climatic conditions projected to be associated with climate change have important implication for human health impact in the Mekong Delta region.
Praseodymium doped CaFe2As2 (122 structure) and CaFeAs2 (112 structure) are characterized by modulated Low Magnetic Field Microwave Absorption (LFMA) spectroscopy. In both (Pr,Ca)122 and (Pr,Ca)112 structures, a strong hysteretic LFMA is found, with a TcH of ∼30 K and ∼26 K, respectively. However, in (Pr,Ca)122, measurements also show an unusual Narrow Peak (NP) LFMA signal appearing at higher temperatures, above the lower TcH superconducting state until a TcNP of 49 K. We associate this NP LFMA with interfacial superconductivity, which has been found previously by highly anisotropic magnetization measurements. Furthermore, the absence of NP in (Pr,Ca)112 correlates with the absence of an interfacial phase. These results give useful information about the microwave signature of interfacial superconductivity present in the (Pr,Ca)122 system, and may form a roadmap towards a stabilized high temperature superconducting phase in pnictides.
Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD) control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent (BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development. (JINS, 2013, 19, 1–14)
The influence of the red and green LED light exposure on the memory function of the nanocrystalline MoOx embedded ZrHfO high-k gate dielectric has been investigated. Since the performance of the device is mainly dependent on the hole trapping and detrapping mechanisms, the light exposure affects the hole generation, transfer, and storage to and in the dielectric structure. Both the charge storage capacity and the leakage current were increased from the light exposure. The Coulomb blockade phenomenon in the leakage current density vs. gate voltage curve disappears under the light exposure condition. The light exposure effect is potentially important for practical application of the device.
This work investigates scanning laser annealing used for ultra-shallow junction (USJ) activation. We investigate the laser system via simulation to determine the peak temperature achieved in the active area during processing. We employed the Sentaurus TCAD software by Synopsys to perform a 2D simulation of a laser scans across the active area of the device, solving the heat equation in both time and space. An absorber layer is deposited on the wafer surface to enhance the absorption of incident energy and reduce SOI reflectivity. An effective absorption coefficient of α=8000cm-1 was calculated for the absorber layer, calibrated with the experimental laser intensity. This absorption coefficient correctly predicts the silicon temperature as a function of power with any arbitrarily defined scan speed. To investigate the role of dopant activation, an SOI wafer was implanted with arsenic 25 keV, dose 3e15 /1.5e15 cm-2 and laser annealed in areas of target temperatures ranging from 850-1300°C. The sheet resistance was measured using 4-point probe showing sheet resistance improvement with increasing laser temperature. The extracted temperature cycle from the 2D heat simulation was used as an equivalent millisecond RTA in a full 3D process simulation to study dopant distribution and activation using Sentaurus Process Kinetic Monte Carlo (KMC), considering the effect of dopants, dopant clusters, and point defects. The results of this simulation demonstrate deactivation of arsenic above 1050°C, which is inconsistent with Hall measurements that suggest increasing laser temperature will increase mobility and activation. The results are analyzed versus the expected trends and suggest future improvements needed to the KMC model or the laser temperature profiles in order to describe activation kinetics in millisecond anneals within SOI.
We present results of first-principles non-equilibrium Green’s function calculations for current-voltage (IV) characteristics of the electrode/HfO2/electrode model systems. In order to investigate the effect of the electrode materials on the IV characteristics, we considered two transition metals for electrode, Ta and W, which are both body-centered-cubic elemental metals but have different valence numbers. We simulated the ON state by placing oxygen vacancies in the HfO2 layer while the OFF state was modeled with HfO2 without oxygen vacancies. At the OFF state, no electric current flowed for -1 V up to +1 V, as expected. At the ON state, however, we found that the absolute current for the Ta electrode was twice as large as that for the W electrode. The analysis of the IV characteristics shows that the electronic coupling between Ta and HfO2 is substantially stronger than that between W and HfO2. Our study demonstrates the importance of the matching between electrode and insulator materials to achieve a high ON- to OFF-current ratio in ReRAMs at a low bias.