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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs.
The ability of the aorta to buffer blood flow and provide diastolic perfusion (Windkessel function) is a determinant of cardiovascular health. We have reported cardiac dysfunction indicating downstream vascular abnormalities in young adult baboons who were intrauterine growth restricted (IUGR) at birth as a result of moderate maternal nutrient reduction. Using 3 T MRI, we examined IUGR offspring (eight male, eight female; 5.7 years; human equivalent 25 years) and age-matched controls (eight male, eight female; 5.6 years) to quantify distal descending aortic cross-section (AC) and distensibility (AD). ANOVA showed decreased IUGR AC/body surface area (0.9±0.05 cm2/m2v. 1.2±0.06 cm2/m2, M±s.e.m., P<0.005) and AD (1.7±0.2 v. 4.0±0.5×10−3/mmHg, P<0.005) without sex difference or group-sex interaction, suggesting intrinsic vascular pathology and impaired development persisting in adulthood. Future studies should evaluate potential consequences of these changes on coronary perfusion, afterload and blood pressure.
The association between Kawasaki disease (KD) and Attention deficit hyperactivity disorder (ADHD) has rarely been studied. In this study, we investigated the hypothesis that KD may increase the risk of ADHD using a nationwide Taiwanese population-based claims database.
Our study cohort consisted of patients who were diagnosed with KD between January 1997 and December 2005 (N = 651). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 3255). The cumulative incidence of ADHD was 3.89/1000 (from 0.05 to 0.85) in this study. All subjects were tracked for 5 years from the date of cohort entry to identify whether or not they had developed ADHD. Cox proportional hazard regression analysis was performed to evaluate 5-year ADHD-free survival rates.
Of all patients, 83 (2.1%) developed ADHD during the 5-year follow-up period, of whom 21 (3.2%) had KD and 62 (1.9%) were in the comparison cohort. The patients with KD seemed to be at an increased risk of developing ADHD (crude hazard ratio (HR): 1.71; 95% confidence interval (CI) = 1.04–2.80; p < 0.05). However, after adjusting for gender, age, asthma, allergic rhinitis, atopic dermatitis and meningitis, the adjusted hazard ratios (AHR) of the ADHD in patients with KD showed no association with the controls (AHR: 1.59; 95% CI = 0.96–2.62; p = 0.07). We also investigated whether or not KD was a gender-dependent risk factor for ADHD, and found that male patients with KD did not have an increased risk of ADHD (AHR: 1.62; 95% CI = 0.96–2.74; p = 0.07) compared with the female patients.
The findings of this population-based study suggest that patients with KD may not have an increased risk of ADHD and whether or not there is an association between KD and ADHD remains uncertain.
Background: The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) offers information on the clinical diagnosis of Alzheimer's disease (AD) and gives a profile of cognitive functioning. This study explores the effects of age, education and gender on participants' performance on eight subtests in the Chinese-Cantonese version of the CERAD-NAB.
Methods: The original English version of the CERAD-NAB was translated and content-validated into a Chinese-Cantonese version to suit the Hong Kong Chinese population. The battery was administered to 187 healthy volunteers aged 60 to 94 years. Participants were excluded if they had neurological, medical or psychiatric disorders (including dementia). Stepwise multiple linear regression analyses were performed to assess the relative contribution of the demographic variables to the scores on each subtest.
Results: The Cantonese version of CERAD-NAB was shown to have good content validity and excellent inter-rater reliability. Stepwise multiple regression analyses revealed that performances on seven and four out of eight subtests in the CERAD-NAB were significantly influenced by education level and age, respectively. Age and education had significant effects on participants' performance on many tests. Gender also showed a significant effect on one subtest.
Conclusions: The preliminary data will serve as an initial phase for clinical interpretation of the CERAD-NAB for Cantonese-speaking Chinese elders.
Outlined here is a technique for sub-wavelength infrared surface imaging
performed using a phase matched optical parametric oscillator laser and an
atomic force microscope as the detection mechanism. The technique uses a
novel surface excitation illumination approach to perform simultaneously
chemical mapping and AFM topography imaging with an image resolution of 200 nm. This method was demonstrated by imaging polystyrene micro-structures.
This work studied the Rayleigh-Bénard convection under the first-order slip boundary conditions in both hydrodynamic and thermal fields. The variation principle was applied to find the critical Rayleigh number of instability. The exteneded relations of the critical Rayleigh number (Rc) and the wavenumber (ac) under partially slip boundary conditions were derived. The numerical results showed that both Rc and ac are decreasing with increasing the Knudsen number. The dependence of Rc on the Knudsen number (K) shows that when K≤10−3, the boundary can be considered as nonslip, while K≥10, it can be considered as free boundaries. The maximum change rate occurs when the Knudsen number is around 0.1, indicating that the system would be affected significantly in that range.
The coupling of hydromagnetic Alfvén waves is studied numerically in a dipolc-field model of the magnetosphere. The two coupled hydromagnetic equations derived by Radoski are solved as an implicit boundary-value problem, namely the boundary conditions at the magnetopause are determined self-consistently. Thus the calculated wave-field distribution inside the magnetosphere can match all known linear characteristic features of the stormtime Pc5 waves observed on 14/15 November 1979 from satellites. A set of proper boundary conditions is found, excellent agreement between the numerical results and observations is demonstrated. Based on the very limited spatial coverage (L ≈ 6·6 and within a latitudinal region ( −10°, 10°)), of the data provided by the satellites, the theoretical model can successfully reconstruct the global micropulsations in the magnetosphere and identify the source regions of hydromagnetic waves.
Background and objectives: Ischaemic preconditioning is commonly regarded as one of the most powerful protective mechanisms against a subsequent lethal ischaemic injury during coronary artery bypass graft surgery but is not practiced routinely. Experimentally, isoflurane, a commonly used volatile anaesthetic agent, provides myocardial protection through a signal transduction cascade that is remarkably similar to the pathways identified in ischaemic preconditioning. The aim of our study was to investigate whether pre-ischaemic administration of isoflurane exerted protection against prolonged ischaemia with functional recovery and reduced necrosis among patients undergoing coronary artery bypass graft surgery. Methods: Forty patients scheduled for elective coronary artery bypass graft operations were prospectively randomized into the control or isoflurane groups. In the isoflurane group, isoflurane 2.5 minimum alveolar concentration was administered for 15 min followed by a 5-min washout period before aortic cross-clamping. The control group received a time-matched period of isoflurane-free cardiopulmonary bypass. The conduction of anaesthesia and surgery were standardized in all patients. Haemodynamic data, troponin I release and inotropic support were measured and recorded perioperatively. Results: There were no adverse effects related to isoflurane administration. In the isoflurane group, the mean cardiac index after cardiopulmonary bypass was significantly higher than the pre-bypass value (P < 0.05), whereas no difference was found in the control group. At 15 min after cardiopulmonary bypass and 6 h after surgery, the changes in cardiac index and stroke volume index were significantly higher in the isoflurane group than in the control group (P < 0.05). There was a consistently lower release of troponin I in the isoflurane group compared to the control group. Compared to the controls, the mean troponin I level was significantly reduced in the isoflurane group at 24 h after surgery (P = 0.042). Conclusions: The present results support the preconditioning effect of isoflurane in patients undergoing coronary artery bypass graft surgery as clinically feasible and providing optimal cardiac protection.
The Arcminute Cosmology Bolometer Array Receiver (Acbar) is a multifrequency millimeter-wave receiver optimized for observations of the Cosmic Microwave Background (CMB) and the Sunyaev-Zel'dovich (SZ) effect in clusters of galaxies. Acbar was installed on the 2.1 m Viper telescope at the South Pole in January 2001 and the results presented here incorporate data through July 2002. The power spectrum of the CMB at 150 GHz over the range ℓ = 150 — 3000 measured by Acbar is presented along with estimates for the values of the cosmological parameters within the context of ΛCDM models. The inclusion of ΩΛ greatly improves the fit to the power spectrum. Three-frequency images of the SZ decrement/increment are also presented for the galaxy cluster 1E0657–67.
Sixty patients were randomly assigned to two equal groups. Group I received epidural morphine 1 mg after surgery and used a patient-controlled analgesia device programmed to deliver morphine 0.2 mg h−1, 0.2 mg per bolus. Group II received an epidural loading dose of morphine 1 mg plus ketamine 5 mg and used a patient-controlled analgesia device programmed to deliver morphine 0.2 mg+ketamine 0.5 mg h−1, morphine 0.2 mg+ketamine 0.5 mg per bolus with a lockout time of 10 min. The mean morphine consumption was 8.6±0.7 mg for group I and 6.2±0.2 mg for group II. Although group II utilized significantly less morphine (P<0.05), pain relief was significantly better in group II than in group I (P<0.05) in the first 3 h. Vomiting occurred more frequently in group I (26%) than in group II (13%). The frequency and severity of pruritus and level of sedation were similar in the two groups. These findings suggest that patient-controlled epidural analgesia with morphine plus ketamine may provide effective analgesia with a lesser dose of morphine and fewer subsequent side effects, compared with patient-controlled epidural analgesia with morphine alone after lower abdominal surgery.
In a moderately rapidly solidified Ga46Fe23Cu23Si8 alloy, a face-centered-cubic (fcc) superstructure (a = 1.78 nm) and a hexagonal superstructure (ahex = 2.18 nm and chex = 0.77 nm), based on the same body-centered-cubic (bcc) γ-brass structure (a = 0.89 nm), were found—by means of micro-area electron diffraction—to coexist with the decagonal quasicrystal. The fcc superstructure is probably similar to one of the F-centered-γ-brass structure and has a parallel orientation relationship with the bcc fundamental structure. The hexagonal superstructure has its (001) parallel to the (111) of the bcc γ-brass structure and its chex = abcc/2, and their lattice correspondence relationship has been derived. Electron diffraction evidence is presented to show that these two superstructures are possibly crystalline approximants of the decagonal quasicrystal.
In this article, we review the recent progress on GaAs MOSFET's using in-situ MBE-grown Ga2O3(Gd2O3) as the gate dielectric. Both depletion-mode (D-mode) and inversion-mode (I-mode) GaAs MOSFET's with negligible drain current drift and hysteresis are demostrated. The absence of drain current drift and hysteresis indicates that the excellent stability of the oxide and low oxide/GaAs interface state density have been achieved. The drain current density and transconductance are about one order of magnitude higher than the best previous reported data in the literature for an inversion-mode GaAs MOSFET. Excellent high frequency and power performances were also measured from the depletion-mode devices. These improvements are attributed to the excellent Ga2O3(Ga2O3) oxide properties and novel processing techniques.
We demonstrate that SiO2 cap rapid thermal annealing in ultra-thin p-type InGaAs/InP quantum wells can be used to produce large blue shifts of the band edge. A substantial bandgap blue shift, as much as 292.5 meV at 900°C has been measured and the value of the bandgap shift can be controlled by the anneal time. Theoretical modeling of the intermixing effect on the energy levels is performed based on the effective bond-orbital method, and we obtain a very good fit to the photoluminescence data. Compared to the as-grown detector, the peak spectral response of the annealed detector was shifted to longer wavelength without any major degradation in the responsivity characteristics.
With the current availability of large-area 3C-SiC films, it is imperative that stable high temperature contacts be developed for high power devices. By comparing the existing data in the literature, we demonstrate that the contact behavior on each of the different polytypes of SiC will vary significantly. In particular, we demonstrate this for 6H-SiC and 3C-SiC. The interface slope parameter, S, which is a measure of the Fermi-level pinning in each system varies between 0.4–0.5 on 6H-SiC, while it is 0.6 on 3C-SiC. This implies that the barrier heights of contacts to 3C-SiC will vary more significantly with the choice of metal than for 6H-SiC.
Aluminum, nickel and tungsten were deposited on 3C-SiC films and their specific contact resistance measured using the circular TLM method. High temperature measurements (up to 400°C) were performed to determine the behavior of these contacts at operational temperatures. Aluminum was used primarily as a baseline for comparison since it melts at 660°C and cannot be used for very high temperature contacts. The specific contact resistance (ρc) for nickel at room temperature was 5 × 10−4 Ω-cm2, but increased with temperature to a value of 1.5 × 10−3 Ω-cm2 at 400°C. Tungsten had a higher room temperature × 10−3 Ω-cm2, which remained relatively constant with increasing temperature up to 400°C. This is related to the fact that there is hardly any reaction between tungsten and silicon carbide even up to 900°C, whereas nickel almost completely reacts with SiC by that temperature. Contact resistance measurements were also performed on samples that were annealed at 500°C.
We report on the OMVPE growth and characterization of AlGalnN and its heterostructures, including measurements of electrical properties (Hall), optical properties (photo- and cathodo- luminescence), structural characteristics (x-ray diffraction and TEM); and also the emission of InGaN/AlGaN heterostructures subject to optical and electrical pumping.
InAsxPi.x/InP (10 period 50/100Å with x=0.25–0.79) pseudomorphically strained multiple quantum wells (SMQWs) were grown by gas source molecular beam expitaxy (GSMBE) at 470°C and characterized by cross-sectional transmission electron microscope (XTEM), double crystal x-ray diffraction (DCXRD), and optical spectroscopy. The structural analysis demonstrates that excellent control of the sharp interface and limited As-P interdiffusion can be achieved by GSMBE growth. XTEM images of these SMQWs display no misfit dislocations, and DCXRD scans reveal high order superlattice satellite peaks. Photoluminescence (PL) and transmission measurements were performed for all SMQWs to evaluate crystal quality. Only slight degradation in luminescence was observed as the As composition increased. Based on the three-band Kane model which includes the lattice strain, the transition energies of SMQWs were calculated using the conduction-band offset (Qc=δEc/δEg) as an adjustable parameter. The best fit of measured and calculated interband transition energies suggests that Qc is independent of As composition and is 0.70±0.05. Finally, a growth kinetics model based on the Langmuir equation was derived to realize the As/P incorporation ratio in the InAsP materials. Theoretical results show good agreement with experimental data.
P-type InGaAs/InP quantum-well infrared photodetectors operated at 4.55 μm require the growth of ultra-thin (10 Å) quantum wells. We report a study of interfaces in QWIPs grown by gas-source molecular beam epitaxy in which we optimized the group V source supply sequence so that a 6 K photoluminescence linewidth as narrow as 8.4 meV was observed from a structure with 10 Å wells. Analysis of the PL suggests that interface roughness was minimized. Cross-sectional scanning tunneling microscopy, double crystal x-ray diffraction, and cross-sectional tunneling electron microscopy confirmed that high-quality interfaces and uniform layers were obtained. Using the derived structural parameters, photocurrent spectral response was theoretically predicted for these QWIPs and then experimentally verified.