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Treatment-resistant schizophrenia, affecting approximately 20–30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.
Introduction: Bronchiolitis is a viral respiratory infection and the most common reason for hospitalization of infants. Despite evidence that few interventions are beneficial in patients with bronchiolitis, other studies would have shown that a significant proportion of patients undergo various forms of low value care. This objective of this project was to 1. establish baseline management of bronchiolitis in the Calgary Zone, and 2. deliver audit and feedback (A&F) reports to pediatric emergency physicians (PEP) to identify opportunities and strategies for practice improvement. Methods: This retrospective cohort study included all patients 12 months old that presented to a Calgary emergency department or urgent care center with a diagnosis of bronchiolitis from April 1, 2013 to March 31, 2017. Using data from various electronic health data sources, we captured age, vital signs, CTAS, common therapeutic interventions (bronchodilators, steroids, antibiotics) and investigations (chest x-ray (CXR), viral studies, antibiotics). Results were stratified by site and by admission status. Descriptive statistics were used to report baseline characteristics and interventions. Interhospital ranges (IHR) were provided to compare different hospitals in the zone. For the A&F component of the project, consenting PEP received a report of both their individual and peer comparator data and an in-person multi-disciplinary facilitated feedback session. Results: We included 4023 patients from all 6 sites (range from 28 to 3316 patients). Admission rates were 21.7% (IHR 0-29%). Mean age was 5.4 months old. Bronchodilator use was 27.0% (IHR 21-41%). 22.0% of patients received a CXR (IHR 0-57%) and 30.3% had viral studies done (IHR range 0.8-33%). PEP had higher usage of viral studies (30% vs 5.7%), whereas non-PEP had higher CXR usage (46.2% vs 23.4%). 41 of 66 PEP consented to receive their individual A&F reports (62%). In the facilitated feedback session PEP 1. identified two areas (bronchodilators and viral studies) where improvements could be made and 2. discussed specific strategies to decrease practice variation and minimize low value care including development of a multi-disciplinary care pathway, alignment with in-patient management, education and repeated A&F reports. Conclusion: Significant variability exists in management of patients with bronchiolitis across different hospitals in our zone. A facilitated feedback session identified areas for improvement and multi-disciplinary strategies to reduced low value care for patients with bronchiolitis. Future phases of this project include repeated data in 6 months and implementation of a provincial care pathway for the management of bronchiolitis.
Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. Family history remains the ‘gold standard’ for both risk stratification and prognosis in complex phenotypes such as depression. Meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. Epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. A heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic–pituitary–adrenal (HPA) axis. The glucocorticoid receptor (GR) gene (NR3C1) has been found to be susceptible to epigenetic modification, specifically DNA methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life.
In this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the HPA axis and the NR3C1 gene. Difficulties with the design of these studies are also explored.
Future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. The complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges.
The work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential DNA methylation patterns in NR3C1 as well as novel therapeutic targets.
Exercise-induced pulmonary haemorrhage (EIPH) is a major health concern in performance horses, but the presence and severity of this condition in racing greyhounds has received little attention. While equids and greyhounds share many physiological attributes, there are important structural and functional differences that may help protect greyhounds from EIPH. We tested the hypothesis that greyhounds performing a simulated 503 m race would experience EIPH and that the time course of recovery would be similar to the horse, even though the severity or relative extent as indexed by the concentration of red blood cells [RBCs] in bronchoalveolar lavage (BAL) fluid would be lower in comparison with that demonstrated previously in horses. Greyhound dogs (n = 6) raced on two occasions (separated by 7 weeks) and BAL was performed 1 week before, 2 h after and each week for 4 weeks following each race to examine the [RBC], concentration of white blood cells [WBCs], WBC differentials and haemosiderophages in the lungs. Racing increased 10 min post-exercise venous blood [lactate] to 18.6 ± 0.4 mmol l− 1. No epistaxis or pink froth was observed at the nose or mouth of any of the dogs. The [RBC] in the BAL fluid was increased significantly 2 h post-race (baseline = 109.6 ± 11.7 × 103; post-race = 292.3 ± 69.9 × 103 RBC ml− 1 BAL fluid, P < 0.05) and returned to baseline 1 week post-race (149.2 ± 46.2 × 103 RBC ml− 1 BAL fluid, P>0.05 versus baseline). The number of haemosiderophages was not different for any of the measurement periods. The [WBC] in the BAL fluid decreased from baseline and race values at 2, 3 and 4 weeks post-exercise (all P < 0.05). Alveolar neutrophil concentrations were also decreased from baseline and immediate post-race values for 4 weeks post-race. The increased [RBC] in the BAL fluid post-exercise is consistent with the presence of EIPH in these greyhounds. However, the relative extent of EIPH in greyhounds (as indexed by [RBC] in the BAL fluid), as compared with that in the horse, was mild, and the lack of elevation of WBC suggests that, unlike their equine counterparts, inflammatory airway disease was absent.
A novel electroactive nanostructured silver molybdenum oxyfluoride (SMOF) perovskite was successfully synthesized via mechanochemistry through the use of AgFx and MoO3. The structure of the SMOF perovskite has been examined utilizing X-ray powder diffraction (XRD) combined with X-ray absorption spectroscopy (XAS) and elemental analysis. The SMOF perovskite exhibited a very good electrochemical activity. A detailed in-situ electrochemical study by XRD and XAS was carried out. Finally, preliminary work on fabrication of a metallic Ag2F phase and optimization of the rate capability of SMOF perovskite is presented.
In this work we present steady-state characteristics and low-frequency noise spectra of AlGaN/GaN based high electron mobility transistors (HEMTs) exposed to gamma ray radiation. The devices with a variety of gate length (150-350 nm) and width (100-400 νm) were irradiated by 60Co gamma rays with doses in the range of 104-109 Rad and flux of 102 Rad/s. Dose dependencies of basic operating parameters of the transistors, such as saturation current (Isat), transconductance (gm), channel conductance (gc), and threshold voltage (VT) are analysed. Our study show that visible changes of above mentioned parameters are observed under relatively small doses (105 Rad) and strongly depend on the HEMT's topology. The transconductance decreases and threshold voltage becomes more negative for all devices while deviation of these parameters from its initial values does not exceed 20% at highest irradiation dose. At the same time variation of the channel conductance as well as saturation current depends to a high extent on the gate voltage (Vg). At |Vg| < |Vcr|, both Isat and gc show a reversal proportional to the cumulative dosage of radiation. However, at |Vg| > |Vcr|, drain saturation current and channel conductance increase with the cumulative dosage of radiation. The effect is more pronounced in short-length-gate devices.
Fossil travertine and subaqueous speleothems in presently dry caves suggest periods of enhanced ground-water recharge during the Quaternary Period in semiarid northeastern Brazil. Travertine deposits and water-table speleothems were dated by the 230Th/234U technique, yielding new evidence for the timing of past periods of increased rainfall. The travertine was deposited in two distinct phases, extensive in situ deposits during marine isotope stage 2 and fragmentary, indurated deposits dating to ca. 400,000 yr B.P. (possibly marine isotope stage 10 or 12). Dating of water-table speleothems showed that the regional water table was 13±1 m above the present level at the last glacial maximum. A second site yielded ages suggesting a still higher water table during marine isotope stage 6. These new data demonstrate that northeastern Brazil did not follow the general pattern of a dry last glacial maximum, as suggested by other continental records in Amazonia and southeastern Brazil, and as depicted in recent General Circulation Model (GCM) simulations. Our results thus indicate that significant variability in regional rainfall patterns occurred in the area during glaciations and caution against overgeneralization of paleoclimate patterns.
Two dimensional hole and electron gases in wurtzite GaN/AlxGa1-xN/GaN heterostructures are induced by strong polarization induced effects. The sheet carrier concentration and the confinement of the two dimensional carrier gases located close to one of the AlGaN/GaN interfaces are sensitive to a high number of different physical properties such as polarity, alloy composition, strain, thickness and doping. We have investigated the structural quality, the carrier concentration profiles and electrical transport properties by a combination of high resolution x- ray diffraction, Hall effect and C-V profiling measurements. The investigated heterostructures with N- and Ga-face polarity were grown by metalorganic vapor phase or plasma induced molecular beam epitaxy covering a broad range of alloy compositions and barrier thickness. By comparison of theoretical and experimental results we demonstrate that the formation of two dimensional hole and electron gases in GaN/AlGaN/GaN heterostructures both rely on the difference of the polarization between the AlGaN and the GaN layer. In addition the role of polarity on the carrier accumulation at different interfaces in n- and p-doped heterostructures will be discussed in detail
Visual markers detectable by histochemical staining have been developed
for analysing the time course and tissue specificity of maize
infections by Fusarium moniliforme. Three F. moniliforme
strains, RRC 374, MRC 826 and RRC PAT, were transformed with a
plasmid, pHPG, containing the gusA reporter gene which codes for
β-glucuronidase (GUS) and the hph gene for hygromycin
resistance as the selectable marker. Introduction of plasmid DNA into germinating
conidia yielded 1·2×10−7
transformants per conidium; expression of both gusA and hph
was however, transient. Stable transformants were obtained using protoplasts
recipient, but transformation frequency was reduced. Southern blot and
PCR analyses confirmed incorporation of pHPG into the
genome of all three F. moniliforme strains with gusA
properly inserted in MRC 826 and RRC PAT, but apparently disrupted in RRC
374. The growth pattern for transformed F. moniliforme isolates
and the parental wild types followed a sigmoid curve on minimal
and enriched media. Hygromycin totally inhibited growth for wild type isolates,
but not of transformants. Transformed isolates
maintained the ability to infect the maize plant. Thus, this study is the
first report of F. moniliforme transformed with a visibly
detectable reporter gene to use for analysing this endophyte-host interaction
of world-wide importance to animal and human health.
The strong spontaneous polarization and piezoelectric effects in the wurtzite IIInitride semiconductors lead to new possibilities for device design. In typical heterojunction field effect transistors these effects are used to create large electron concentrations at the AlGaN/GaN interface. However, we examine several other possible device structures which include heterojunctions of AlGaN, GaN, and InGaN. For example, we find the strong electric fields present in these structures allow us to create quantum wells greater than 1 eV deep. Both Ga-faced and N-faced materials are explored. The two-dimensional electron gas concentrations in these structures are found using a self-consistent 1-D Schrödinger-Poisson solver modified to incorporate the effects of spontaneous and piezoelectric polarization. The boundary conditions at the heterojunction interfaces and at the surface and substrate are discussed in detail. Electron concentrations are compared with those obtained experimentally through capacitance-voltage and Hall effect measurements.
Selective Area Flow Modulation Epitaxial growth of GaN is carried out in a low pressure Organometallic Vapor Phase Epitaxy reactor. This process is known to enhance reactant surface migration lengths on patterned group III-arsenide and phosphide growth surfaces. With this process, high quality laterally overgrown GaN epitaxial materials result. Under the ammonia rich growth conditions used, enhanced migration (by flux modulation) across masked regions of the substrate has not been observed. The mask materials were silicon dioxide and silicon nitride, both deposited on GaN/AlGaN buffer structures on sapphire and SiC substrates. Window stripes were patterned parallel and perpendicular to the (1100) crystal directions to observe the orientation dependence of the lateral growth rate. Structures exhibited heights above the mask surface as large as 30 microns and atomically smooth surfaces. With a periodic array of stripe window openings in the mask, planarized laterally overgrown surfaces are achieved after roughly 4 microns of overgrowth. Chemical assisted ion beam etching with chlorine gas was used to delineate defects in the selectively grown layers. Additional evidence on the defect reduction is given by Atomic Force and Scanning Transmission Electron Microscopies.
The key parameters of GaN for use in microwave power amplifiers are presented. The electron-scattering effect of dislocations are presented for 2 DEG in HEMT devices. The use of the piezoelectric effect in designing Aly Ga1-yN/GaN HEMT structures is reviewed for a range of y.Short-gate device fabrication methods, and the device characterization, are presented. Maximum frequency of oscillation for .15 μm gates reached 140 GHz, while .3 μm gate power amplifiers reached 74% power-added efficiency at 3 GHz.
In this paper we give an algorithm for computing the 2-Selmer group of an elliptic curve
which has complexity O(LD(0·5),c1)), where D is the absolute discriminant of the curve. Our algorithm is unconditional but the complexity estimate assumes the GRH and a standard conjecture on the distribution of smooth reduced ideals. This improves on the corresponding algorithm of Birch and Swinnerton-Dyer, which has complexity of O(√D).
The state of the art (SOA) Li-ion cells utilize carbon anodes. However, to improve specific energy, energy density, and safety of cells using carbon anodes, alternative anodes must be developed. Recently, Fuji Film Inc. has suggested the use of tin oxide based anodes in Li-ion cells. It is believed mat cells containing tin oxide based anodes have the potential to meet the need for NASA's future missions. As a result, we conducted an analysis to compare the performance of cells containing carbon anodes and cells containing tin oxide anodes. The comparison between these cells involved the following: 1) reaction mechanisms between Li and carbon and reaction mechanisms between Li and tin oxide, 2) half-cell and full-cell performance characteristics, 3) interactions between the anode materials and electrolyte types and compositions, and 4) the optimization of binder composition.
Molecular mobility of water and trimethoxymethane (TMM) in NAFION membranes of two different equivalent weights (EW), 1100 and 1500, were investigated. Self-diffusion coefficients were determined by the NMR pulsed field gradient method, using the water and methyl protons NMR signals, in saturated NAFION samples containing concentrations of TMM in water varying between 0.5 and 14 M, and at temperatures varying from 30°C to 80°C. Diffusion of molecular species containing methyl protons is more than a factor of two slower in the 1500 EW membrane than in the 1100 EW membrane at 30°C and 1 M concentration. The difference rises to about a factor of four at 80°C and 14 M concentration. These differences are attributed to the lower extent of plasticization of the higher EW material as well as the greater effective distance between acid functional groups. NAFION samples containing methanol/water mixtures were also investigated. Comparison with the methanol results and the permeation behavior, as characterized by gas Chromatographie methods, show that more than half of the TMM is hydrolyzed to methanol as it passes through the acidic membrane. The implications of these findings for alternative fuels in direct oxidation fuel cells are discussed.