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Schools are important settings for increasing reach and uptake of adolescent mental health interventions. There is limited consensus on the focus and content of school-based mental health services (SBMHSs), particularly in low-resource settings. This study elicited the views of diverse stakeholders in two urban settings in India about their priorities and preferences for SBMHSs.
We completed semi-structured interviews and focus group discussions with adolescents (n = 191), parents (n = 9), teachers (n = 78), school counsellors (n = 15), clinical psychologists/psychiatrists (n = 7) in two urban sites in India (Delhi and Goa). Qualitative data were obtained on prioritized outcomes, preferred content and delivery methods, and indicated barriers.
All stakeholders indicated the need for and acceptability of SBMHSs. Adolescents prioritized resolution of life problems and exhibited a preference for practical guidance. Parents and teachers emphasized functional outcomes and preferred to be involved in interventions. In contrast, adolescents' favored limited involvement from parents and teachers, was related to widespread concerns about confidentiality. Face-to-face counselling was deemed to be the most acceptable delivery format; self-help was less frequently endorsed but was relatively more acceptable if blended with guidance or delivered using digital technology. Structured sensitization was recommended to promote adolescent's engagement. Providers endorsed a stepped care approach to address different levels of mental health need among adolescents.
SBMHSs are desired by adolescents and adult stakeholders in this setting where few such services exist. Sensitization activities are required to support implementation. School counsellors have an important role in identifying and treating adolescents with different levels of mental health needs, and a suite of interventions is needed to target these needs effectively and efficiently.
To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.
Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.
Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).
Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Although quality of life (QoL) is receiving increasing attention in bipolar disorder (BD) research and practice, little is known about its naturalistic trajectory. The dual aims of this study were to prospectively investigate: (a) the trajectory of QoL under guideline-driven treatment and (b) the dynamic relationship between mood symptoms and QoL.
In total, 362 patients with BD receiving guideline-driven treatment were prospectively followed at 3-month intervals for up to 5 years. Mental (Mental Component Score – MCS) and physical (Physical Component Score – PCS) QoL were measured using the self-report SF-36. Clinician-rated symptom data were recorded for mania and depression. Multilevel modelling was used to analyse MCS and PCS over time, QoL trajectories predicted by time-lagged symptoms, and symptom trajectories predicted by time-lagged QoL.
MCS exhibited a positive trajectory, while PCS worsened over time. Investigation of temporal relationships between QoL and symptoms suggested bidirectional effects: earlier depressive symptoms were negatively associated with mental QoL, and earlier manic symptoms were negatively associated with physical QoL. Importantly, earlier MCS and PCS were both negatively associated with downstream symptoms of mania and depression.
The present investigation illustrates real-world outcomes for QoL under guideline-driven BD treatment: improvements in mental QoL and decrements in physical QoL were observed. The data permitted investigation of dynamic interactions between QoL and symptoms, generating novel evidence for bidirectional effects and encouraging further research into this important interplay. Investigation of relevant time-varying covariates (e.g. medications) was beyond scope. Future research should investigate possible determinants of QoL and the interplay between symptoms and wellbeing/satisfaction-centric measures of QoL.
Individuals with chronic respiratory conditions may be at increased risk for pertussis. We conducted a retrospective administrative claims analysis to examine the incidence and economic burden of diagnosed pertussis among adolescents and adults in the USA with chronic obstructive pulmonary disease (COPD) or asthma. Patients aged ⩾11 years with diagnosed pertussis and pre-existing COPD (n = 343) or asthma (n = 1041) were matched 1:1 to patients with diagnosed pertussis but without COPD or asthma. Differences in all-cause costs (‘excess’ costs) during the 45-day and 3-month and 6-month periods before and after the pertussis index date were calculated; adjusted excess costs were estimated via multivariate regressions. The incidence of diagnosed pertussis was higher among patients with COPD or asthma than among matched patients. Compared with matched patients, patients with pertussis and pre-existing COPD or asthma accrued greater all-cause adjusted costs across study periods ($3694 and $1193 more, respectively, in the 45-day period; $4173 and $1301 more in the 3-month period; and $6154 and $1639 more in the 6-month period; all P < 0·0001). Patients with pre-existing COPD or asthma experience an increased economic burden after diagnosed pertussis and may especially benefit from targeted tetanus, diphtheria, and acellular pertussis vaccination strategies.
We discuss atomistic aspects of the silicide contact reaction inferred primarily from STM observations of the prototype system Co/Si(1 11). For room temperature deposition and low coverage (0.01M1) we find that metal atoms exist as near-surface interstitials within the 7×7 reconstruction. Bond breaking associated with silicide formation occurs only at higher coverages. Deposition at 320C results in flat-topped triangular islands of epitaxial CoSi2 with a metastable 7-fold (111) interface, stabilized by the lateral silicon-silicide interface along the island edges. Some islands are covered with a 2×2 array of silicon adatoms. Very high temperature annealing (1200C) results in an “impurity stabilized 1×1” surface which is in fact a lattice gas of ring-clusters that appear like tiny donuts or bagels in empty states STM images. These structures phase-separate from the clean 7×7 structure upon cooling below 850C.
As the group III nitride semiconductor technology matures, an increasing number of devices are being fabricated with high Al fraction AlGaN. In this study, ohmic behavior is achieved using Ti/Al/Pt/Au contacts to n-Al0.4Ga0.6N, which is the highest Al fraction for which ohmic contact formation has been reported. The effect of contact composition, pretreatment, and annealing conditions is studied by 30 s isochronal annealing experiments between 500°C and 1000°C. A specific contact resistance ρC of (5±3) × 10−5 ωcm2 is obtained using Ti(26 nm)/Al(74 nm)/Pt(50 nm)/Au(50 nm) contacts to n-Al0.4Ga0.6N annealed in N2 at 800°C; however, this value is shown to be artificially high because the metal sheet resistance RM is 4 ω/⊏ causing an artifact in the data analysis. All contacts with ρC < 10−3 ωcm2 exhibit a local minimum in ρC after annealing at 800°C. The observed increase in ρC upon annealing at 850°C and 900°C, however, is not an artifact originating from a change in RM. The top Au layer is found to play an active role in forming ohmic contacts with low ρC, since omitting the Au layer yields an increase in ρC of two orders of magnitude after annealing at 800°C. Furthermore, leaving out the Au layer requires an annealing temperature of 700°C to result in linear I-V curves for currents up to 100 µA, as opposed to 500°C when the Au layer is present. The role of Au is further studied in Ti(26 nm)/Al(74 nm)/Ni(50 nm)/Au(50 nm) contacts, where Rutherford backscattering spectroscopy reveals Ga in the metal layer and/or Au buried deeper than the original semiconductor-metal interface, and x-ray diffraction indicates the formation of new phases to happen concurrently with a decrease in ρC of three orders of magnitude.
Ionization energies and electron affinities of clean AlxGa1−xN(0001) surfaces were investigated by ultraviolet photoemission spectroscopy over the whole composition range. The samples were cleaned with cycles of N+-ion sputtering and annealing partly within a Ga atom flux. The ionization energy is measured as 6.5 eV and is almost independent of the aluminum content in good agreement with the general chemical trend. The electron affinity decreases linearly with composition from 3.1 eV for GaN to 0.25 eV for AlN. No evidence for negative electron affinity at AlN(0001) surfaces was found. Adsorption of oxygen at room temperature leads to a significant increase of the ionization energy and electron affinity. With AlN(0001) surfaces, an oxygen uptake of 0.6 monolayers is observed after exposures of 108 Langmuirs and the ionization energy increases by approximately 2 eV.
The availability of reliable and quick methods to investigate defects in GaN films is of great interest. Photo-electrochemical (PEC), and hot wet etching using both H3PO4 acid and molten KOH have been used to study structural defects in GaN layers grown by hydride vapor phase epitaxy and molecular beam epitaxy. The purpose of this work is to determine whether, and under what conditions, these different methods of investigation are consistent and to get to a more accurate estimation of the defect density. As-grown and etched surfaces were investigated by atomic force microscopy (AFM), and plan-view and cross-sectional transmission electron microscopy (TEM). Free-standing whisker-like features and hexagonal etch pits were formed on the etched sample surfaces by PEC and wet etching, respectively. Using plan-view AFM, we found the density of whiskers (8x108-1×109 cm−2) to be similar to the etch pit densities when etched in both H3PO4 and molten KOH under precise etching conditions. During the wet etching process, a careful balance must be struck to ensure that every defect is delineated, but not overetched to cause merging which would lead to an underestimation of the defect density. Additionally, TEM observations confirmed the dislocation densities obtained by etching, which increased our confidence in the consistency of the methods used.
Structural, electrical and optical properties of free-standing 200-μm thick GaN films grown by hydride vapor phase epitaxy (HVPE) have been investigated. After laser lift-off, the GaN substrates were mechanically polished on both Ga and N-sides and dry etched only on the Ga- side to obtain a smooth epi-ready surface. Hot H3PO4 chemical etching on both surfaces was used to reveal the defect sites, which appeared as hexagonal pits. The etched surfaces were then examined by atomic force microscopy. A few seconds of etching was sufficient to smooth the N- face surface and produce etch pits with a density of ≈ 1×107 cm−2. In contrast, a 50 minute etching was needed to delineate the defect sites on the Ga-face which led to a density as low as 5×105 cm−2. From plan-view and cross-sectional transmission electron microscopy (TEM) analysis, we have estimated that the dislocation density is less than about 5×106 cm−2 and ≈ 3×107 cm−2 for the Ga and N-faces respectively. The full-width at half-maximum (FWHM) of the symmetric (0002) X-ray diffraction rocking curve was 69 and 160 arcsec for the Ga and N-faces, respectively. That for the asymmetric (10 4) peak was 103 and 140 arcsec for Ga and N-faces, respectively. Hall measurements demonstrated very high mobility (1100 and 6800 cm2/V.s at 295 and 50 K, respectively) and very low concentration of donors (2.1×1016 cm−3) and acceptors (4.9×1015 cm−3). In the photoluminescence (PL) spectrum taken at 10 K, a rich excitonic structure has been observed with the highest peak attributed to the exciton bound to neutral shallow donor (BDE). The FWHM of the BDE peak was about 1.0 meV on the Ga face before and after hot chemical etching, whereas that on the N-face decreased from about 20 to 1.0 meV after chemical etching owing to the removal of the surface damage originated from the mechanical polishing.
Properties of GaN layers grown by metalorganic chemical vapor deposition (MOCVD) on c-plane of sapphire have been investigated using atomic force microscopy (AFM), wet etching for defect investigation, transmission electron microscopy (TEM), high-resolution X-ray diffraction, Hall effect measurements and low-temperature photoluminescence (PL). Tapping-mode AFM images of the as-grown samples showed atomically smooth surfaces (rms roughness ≍ 0.2 nm) consisting of terraces separated by about 3Å bi-layer steps. Hot H3PO4 chemical etching was used to produce hexagonal-shaped etch pits at the surface defect sites as revealed by AFM imaging. The obtained etch pit densities (9×108 - 2 ×109 cm−2) were in agreement with the dislocation density found by plan-view and cross-sectional TEM observations. The full-width at half-maximum (FWHM) of the X-ray diffraction rocking curve was about 4.8 and 3.9 arcmin for the symmetric (002) and asymmetric (104) directions, respectively. PL spectrum at 15 K demonstrated sharp peaks (FWHM ≍ 4 meV) in the excitonic region, which were attributed to free and bound excitons. The spectrum contained also weak PL bands with maxima at about 2.2, 2.9 and 3.27 eV, which have been attributed to three different acceptors.
Ohmic contacts and Schottky contacts were made on an undoped AlGaN/GaN FET structure. Despite the high Al content (33%), we were still able to obtain a contact resistance of 0.3 ωmm. Pulsed measurements showed the large effect of self-heating even for circular contacts with a radius of 50 μm. The behavior ofthe Ni/Au Schottky contacts is according to the charge control model; the reverse current and capacitanceonly scale with the area of the diode. Tests with polygon type diodes showed no dependence of the reverse current on the number of polygon corners. The reverse current decreased when the devices were aged at 400°C for 30 hrs. Coplanar Waveguide discontinuities were realized on AlN substrates. A scalable lumped element model was derived from measurements for T-junctions, transmission lines, bends and crosses.
Hall-effect measurements were conducted on Si-doped AlxGa1−xN films grown on sapphire substrate by gas source molecular beam epitaxy. The Al mole fraction in the 1 [.proportional]m thick AlxGa1−xN was 0.0, 0.3, and 0.5, and the Si doping concentration was kept at a nominal value of 1018 cm−3. Variable temperature Hall-effect measurements reveal a presence of a highly degenerate n-type region at the AlxGa1−xN /sapphire interface. This degenerate interfacial layer dominates the electrical properties below 30 K and significantly affects the properties of the AlxGa1−xN layer. Thus, by using a two-layer conducting model, the carrier concentration and mobility of the AlxGa1−xN layer alone are obtained.
Substrate preparation of GaN, both in-situ and ex-situ, and the growth of gadolinium oxide, Gd2O3, by Gas source molecular beam epitaxy (GSMBE) have been investigated. Ex-situ cleaning techniques included wet chemical etching and UV-ozone treatments to remove surface contaminants and the native oxide. In-situ cleaning consisted of thermal treatment with and without exposure to an electron cyclotron resonance (ECR) oxygen plasma. A GaN (1x3) streaky RHEED pattern was the final product of this surface treatment study. Various growth initiation techniques were explored to produce Gd2O3 films with different microstructures as evidenced by RHEED, TEM, and XRD. Gd2O3 films planarized the initial GaN surface and stoichiometry was maintained over a range of substrate temperatures (300° to 650°C). Single crystal gadolinium oxide films were grown at substrate temperatures of 600-650°C. These films exhibited a breakdown field strength (EBD) of ∼1MV/cm, and showed high leakage current at high forward bias due to defects within the oxide. Single crystal oxide films were found to be thermally stable at annealing temperatures up to 1000°C. Quasi-amorphous films were grown at a substrate temperature of 100°C. These films exhibited a higher E BD of ∼3MV/cm and an interface state density of 3 × 1011 cm−2eV−1. However, the quasi-amorphous films were not thermally stable at 1000°C, showing evidence of re-crystallization in x-ray diffraction (XRD) scans.
A systematic investigation of the damage accumulation in GaN films induced by 150keV Ar ions as a function of implantation temperature and dose rate has been conducted. The depth distribution of the disorder in the Ga sublattice has been measured by RBS/channeling spectrometry with a glancing angle detector geometry to provide enhanced depth resolution. Two disordered regions were identified in the damage depth distribution: a near-surface peak and a bulk damage peak. These regions exhibit different behavior as a function of implantation temperature. The height of the near-surface peak, as expected, decreased with implantation temperature approaching the magnitude of the unimplanted sample. The displaced atomic density in the bulk damage peak also followed this tendency and decreased in the temperature range from room temperature to 500°C. The implantation at higher temperatures resulted in an increase in the amount of damage, reaching a maximum at about 700°C and displayed a characteristic “reverse annealing” behavior. Further increase of the implantation temperature to 1000oC reduced the disorder. The influence of the dose rate and implantation temperature on the radiation damage accumulation is discussed.
We have studied radiative and nonradiative recombination at surface states in GaN, including as-grown samples and those treated with acids or bases. The surface states manifested themselves in two ways: (i) a reversible increase of the photoluminescence (PL) intensity after ultraviolet (UV) illumination in vacuum and (ii) appearance of new PL bands after treatment with acid or base and subsequent exposure to air. It has been established that the GaN surface physi-sorbs species from air (presumably oxygen) which induce surface states acting as nonradiative recombination centers. It has been found that nonradiative recombination of photogenerated carriers via surface states comprises more than 70% of the recombination in some GaN samples. Another type of the surface state, which participates in radiative recombination, has been found in GaN samples with Ga polarity after brief etching of the surface with hot acid or base and subsequent exposure to air. In such samples, a broad PL band emerges in the blue region of the spectrum at low temperatures. The blue band has been attributed to transitions of photogenerated electrons from donors in the near-surface depletion region to the surface states introduced by the above-mentioned procedure. The changes in the GaN surface caused by etching were examined by atomic force microscopy. In some samples the blue band appeared even when no evidence of the layer etching was found except for quite shallow etch pits formed at dislocation sites. The emerging blue band can be related to the surface states formed on the a-planes of etch pits.