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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.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
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.
Results
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.
Conclusions
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.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
As evidence for the second process of the Embracing factor, the target article characterizes being moved as a mixed emotion linked to sadness through metonymy. We question these characterizations and argue that emotions should not be equated with their vernacular labels.
A benthic foraminiferal fauna of 39 species was quantitatively examined from a late Pleistocene marine terrace deposit near Goleta, California. This foraminiferal fauna, dominated by Cribroelphidium microgranulosum, Buccella tenerrima, Buliminella elegantissima, and Cribroelphidium tumidum, is presently most common in cool, shallow (<12 m, but usually 0–5 m) subtidal environments north of Point Conception, California. This indicates slightly cooler water temperatures during the time of deposition than found near Goleta today, and agrees closely with the results of a previous paleoenvironmental interpretation of the section based on molluscan fossils.
Oblique-angle deposition is used to fabricate indium tin oxide (ITO) optical coatings with a porous, columnar nanostructure. Nanostructured ITO layers with a reduced refractive index are then incorporated into antireflection coating (ARC) structures with a step-graded refractive index design, enabling increased transmittance into an underlying semiconductor over a wide range of wavelengths of interest for photovoltaic applications. Low-refractive index nanostructured ITO coatings can also be combined with metal films to form an omnidirectional reflector (ODR) structure capable of achieving high internal reflectivity over a broad spectrum of wavelengths and a wide range of angles. Such conductive high-performance ODR structures on the back surface of a thin-film solar cell can potentially increase both the current and voltage output by scattering unabsorbed and emitted photons back into the active region of the device.
Young people who are born very preterm exhibit a narrower arterial tree as compared with people born at term. We hypothesized that such arterial narrowing occurs as a direct result of premature birth. The aim of this study was to compare aortic and carotid artery growth in infants born preterm and at term. Observational and longitudinal cohort study of 50 infants (21 born very preterm, all appropriate for gestational age, 29 controls born at term) was conducted. Diameters of the upper abdominal aorta and common carotid artery were measured with ultrasonography at three months before term, at term and three months after term-equivalent age. At the first assessment, the aortic end-diastolic diameter (aEDD) was slightly larger in very preterm infants as compared with fetal dimensions. Fetal aortic EDD increased by 2.6 mm during the third trimester, whereas very preterm infants exhibited 0.9 mm increase in aEDD during the same developmental period (P < 0.001 for group difference). During the following 3-month period, aortic growth continued unchanged (+0.9 mm) in very preterm infants, whereas postnatal growth in term controls slowed down to +1.3 mm (P < 0.001 v. fetal aortic growth). At the final examination, aEDD was 22% and carotid artery EDD was 14% narrower in infants born preterm compared with controls, also after adjusting for current weight (P < 0.01). Aortic and carotid artery growth is impaired after very preterm birth, resulting in arterial narrowing. Arterial growth failure may be a generalized vascular phenomenon after preterm birth, with implications for cardiovascular morbidity in later life.
To harness the full spectrum of solar energy, optical reflections at the surface of a solar photovoltaic cell must be reduced as much as possible over the relevant solar spectral range and over a wide range of incident angles. The development of antireflection coatings embodying omni-directionality over a wide range of wavelengths is challenging. Recently, nanoporous films, fabricated by oblique-angle deposition and having tailored- and very low-refractive index properties, have been demonstrated. Tailorability of the refractive index and the ability to realize films with a very low-refractive index are properties critical in the performance of broadband, omnidirectional antireflection coatings. As such, nanoporous materials are ideally suited for developing near-perfect antireflection coatings. Here, we discuss multilayer antireflection coatings with near-perfect transmittance over the spectral range of 400−2000 nm and over widely varying angles of acceptance, 0−90°. The calculated solar optical-to-electrical efficiency enhancement that can be attained with nanoporous multilayer coatings over single-layer quarter-wave films is 18%, making these coatings highly attractive for solar cell applications.
Contact tracing of persons with meningococcal disease who have travelled on aeroplanes or other multi-passenger transport is not consistent between countries. We searched the literature for clusters of meningococcal disease linked by transient contact on the same plane, train, bus or boat. We found reports of two clusters in children on the same school bus and one in passengers on the same plane. Cases within each of these three clusters were due to strains that were genetically indistinguishable. In the aeroplane cluster the only link between the two cases was through a single travel episode. The onset of illness (2 and 5 days after the flight) is consistent with infection from an unidentified carrier around the time of air travel. In contrast to the established risk of transmission from a case of tuberculosis, it is likely that the risk from a case of meningococcal disease to someone who is not identified as a close contact is exceedingly low. This should be considered in making international recommendations for passenger contact tracing after a case of meningococcal disease on a plane or other multi-passenger transport.
This study investigated whether ‘unwanted pregnancy’ (i.e. a negative or ambivalent attitude towards the pregnancy/reproduction) is associated with schizophrenia-spectrum and affective disorders in the offspring in adulthood, and if so, whether other pregnancy, perinatal, childhood or genetic-risk factors account for this association.
Method
In a prospective study beginning during pregnancy, unwanted pregnancy (in combination with other early life risk factors) was studied in relation to adult mental disorders in 75 genetic high-risk (HR) and 91 normal-risk (NR) offspring, defined through maternal psychosis history. Early life risk factors were studied through personal interviews, observations and medical records, and offspring mental disorders were independently diagnosed through follow-up examination at about 22 years of age.
Results
Unwanted pregnancy by itself was significantly related to adult offspring schizophrenia-spectrum disorders in both the total sample and the HR subgroup, but the effect was found to be limited to the HR group and occurred in interaction with genetic risk. Other co-temporaneous pregnancy stressors and later perinatal complications, malformations and early childhood environmental stressors could not explain this relationship. Unwanted pregnancy also interacted with genetic-risk status in relating to affective disorders in the offspring.
Conclusions
Unwanted pregnancy, when occurring together with genetic risk for psychosis, was found to be related to both adult schizophrenia-spectrum and affective mental disorders in the offspring. Although the effect of unwanted pregnancy could be mediated by other yet-unidentified factors, unwanted pregnancy might be a functional, discrete environmental psychosocial factor with its own deleterious impact on offspring mental development, when co-occurring with genetic risk.
We compute the axisymmetric convective motions that exist in a spherical shell heated from below with inner to outer radius ratio equal to 0.5. The boundaries are stress-free and gravity is directly proportional to radius. Accurate solutions at large Rayleigh numbers (O(105)) are made feasible by a spectral method that employs diagonal-mode truncation. By examining the stability of axisymmetric motions we conclude that the preferred form of convection varies dramatically according to the value of the Rayleigh number. While axisymmetric motions with different patterns may exist for modestly nonlinear convection, only a single motion persists at sufficiently large values of the Rayleigh number. This circulation is symmetric about the equator and has two meridional cells with rising motion at the poles. Instability of this single axisymmetric motion determines that the preferred pattern of three-dimensional convection has one azimuthal wave.
The approximations implicit in Bénard convection have been modified to include viscous dissipation. It is shown that both the influence of an adiabatic temperature gradient and of viscous dissipation are governed by the same dimensionless parameter Di = αgh/cp. Numerical calculations of finite amplitude convection are given for finite values of Di. It is found that increasing Di decreases flow velocities and finally stabilizes the flow.
Ultraviolet light-emitting diodes (UV LEDs) with AlxGa1−xN/AlyGa1−yN multiple quantum well (MQW) active regions, doped in the barriers with different Si doping level, show a sharp near band-edge emission (UV luminescence). Besides the near band-edge emission, some samples also show parasitic emissions with a broad peak centered at about 520 nm (green luminescence). The EL intensities of the UV emission line and the green emission line are studied. The UV luminescence peak intensity increases superlinearly with the injection current, following a power law with an exponent of about 2.0. In contrast, the green luminescence peak intensity increases linearly with the injection current, with an exponent of about 1.0. A theoretical model is proposed to explain the relationship between the peak intensities and the injection current. The results obtained from the model are in excellent agreement with the experimental results. The model provides a method to evaluate the dominant recombination process by measuring the exponent of the power-law dependence.
Nanoparticle-loaded encapsulants provide unique optical and material properties for the enhancement of light extraction efficiency in light-emitting diodes (LEDs). We report on the uniform dispersion of TiO2 nanoparticles with average diameter of 40 nm in epoxy, and the demonstration of a refractive index (n)of 1.68 at 400 nm wavelength, higher than that of pure epoxy (n = 1.53). It is found that proper chemical surfactants and nanoparticle preparation are critical to eliminate agglomeration of nanoparticles. Theoretical analysis of optical scattering in nanoparticle-loaded encapsulation materials reveals that although the size and loading factor of nanoparticles greatly influence scattering, specular transparency of the encapsulant film occurs if the thicknesses of the films are kept below the optical scattering length. Furthermore, the encapsulants benefit from an optimized scattering coefficient as demonstrated by three-dimensional ray-tracing simulations showing light extraction efficiency enhancements greater than 50%.
The effect of the density and in-plane distribution of interfacial interactions on crack initiation in an epoxy-silicon joint was studied in nominally pure shear loading. Well-defined combinations of strong (specific) and weak (nonspecific) interactions were created using self-assembling monolayers. The in-plane distribution of strong and weak interactions was varied by employing two deposition methods: depositing mixtures of molecules with different terminal groups resulting in a nominally random distribution, and depositing methyl-terminated molecules in domains defined lithographically with the remaining area interacting through strong acid-base interactions. The two distributions lead to very different fracture behavior. For the case of the methyl-terminated domains (50 μm on a side) fabricated lithographically, the joint shear strength varies almost linearly with the area fraction of strongly interacting sites. From this we infer that cracks nucleate on or near the interface over nearly the entire range of bonded area fraction and do so at nearly the same value of local stress (load/bonded area). We postulate that the imposed heterogeneity in interfacial interactions results in heterogeneous stress and strain fields within the epoxy in close proximity to the interface. Simply, the bonded areas carry load while the methyl terminated domains carry negligible load. Stress is amplified adjacent to the well-bonded regions (and reduced adjacent to the poorly bonded regions), and this leads to crack initiation by plastic deformation and chain scission within the epoxy near the interface. For the case of mixed monolayers, the dependence is entirely different. At low areal density of strongly interacting sites, the joint shear strength is below the detection limit of our transducer for a significant range of mixed monolayer composition. With increasing density of strongly interacting sites, a sharp increase in joint shear strength occurs at a methyl terminated area fraction of roughly 0.90. We postulate that this coincides with the onset of yielding in the epoxy. For methyl-terminated area fractions less than 0.85, the joint shear strength becomes independent of the interfacial interactions. This indicates that fracture no longer initiates on the interface but away from the interface by a competing mechanism, likely plastic deformation and chain scission within the bulk epoxy. The data demonstrate that the in-plane distribution of interaction sites alone can affect the location of crack nucleation and the far-field stress required.
The effect of high temperature, high pressure annealing on morphology, optical and structural properties of free-standing GaN films grown by hydride vapor phase epitaxy is studied. The annealing is found to change the intensities of the photoluminescence peaks as a result of a redistribution of the impurities and native defects in the thick GaN films. A positron annihilation study shows a decrease of the Ga vacancy-related defects below the detection limit after the annealing. The defect redistribution is correlated with a flattening of the stress distribution across the thickness, as revealed by micro Raman study, and with a decrease of the curvature of the annealed free-standing films.