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Increasing interest in three-dimensional nanostructures adds impetus to electron microscopy techniques capable of imaging at or below the nanoscale in three dimensions. We present a reconstruction algorithm that takes as input a focal series of four-dimensional scanning transmission electron microscopy (4D-STEM) data. We apply the approach to a lead iridate, Pb$_2$Ir$_2$O$_7$, and yttrium-stabilized zirconia, Y$_{0.095}$Zr$_{0.905}$O$_2$, heterostructure from data acquired with the specimen in a single plan-view orientation, with the epitaxial layers stacked along the beam direction. We demonstrate that Pb–Ir atomic columns are visible in the uppermost layers of the reconstructed volume. We compare this approach to the alternative techniques of depth sectioning using differential phase contrast scanning transmission electron microscopy (DPC-STEM) and multislice ptychographic reconstruction.
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.
Coronary artery aneurysms are well-described in Kawasaki disease and the Multisystem Inflammatory Syndrome in Children and are graded using Z scores. Three Z score systems (Boston, Montreal, and DC) are widely used in North America. The recent Pediatric Heart Network Z score system is derived from the largest diverse sample to-date. The impact of Z score system on the rate of coronary dilation and management was assessed in a large real-world dataset.
Methods:
Using a combined dataset of patients with acute Kawasaki disease from the Children’s Hospital at Montefiore and the National Heart, Lung, and Blood Institute Kawasaki Disease Study, coronary Z scores and the rate of coronary lesions (Z ≥ 2.0) and aneurysms (Z ≥ 2.5) were determined using four Z score systems. Agreement among Z scores and the effect on Kawasaki management were assessed.
Results:
Of 333 patients analysed, 136 were from Montefiore and 197 from the Kawasaki Disease Study. Age, sex, body surface area, and rate of coronary lesions did not differ between the samples. Among the four Z score systems, the rate of acute coronary lesions varied from 24 to 55%. The mean left anterior descending Z scores from Pediatric Heart Network and Boston had a large uniform discrepancy of 1.3. Differences in Z scores among the four systems may change anticoagulation management in up to 22% of a Kawasaki population.
Conclusions:
Choice of Z score system alone may impact Kawasaki disease diagnosis and management. Further research is necessary to determine the ideal coronary Z score system.
We investigate the dynamics of cohesive particles in homogeneous isotropic turbulence, based on one-way coupled simulations that include Stokes drag, lubrication, cohesive and direct contact forces. We observe a transient flocculation phase, followed by a statistically steady equilibrium phase. We analyse the temporal evolution of floc size and shape due to aggregation, breakage and deformation. Larger turbulent shear and weaker cohesive forces yield smaller elongated flocs. Flocculation proceeds most rapidly when the fluid and particle time scales are balanced and a suitably defined Stokes number is $O(1)$. During the transient stage, cohesive forces of intermediate strength produce flocs of the largest size, as they are strong enough to cause aggregation, but not so strong as to pull the floc into a compact shape. Small Stokes numbers and weak turbulence delay the onset of the equilibrium stage. During equilibrium, stronger cohesive forces yield flocs of larger size. The equilibrium floc size distribution exhibits a preferred size that depends on the cohesive number. We observe that flocs are generally elongated by turbulent stresses before breakage. Flocs of size close to the Kolmogorov length scale preferentially align themselves with the intermediate strain direction and the vorticity vector. Flocs of smaller size tend to align themselves with the extensional strain direction. More generally, flocs are aligned with the strongest Lagrangian stretching direction. The Kolmogorov scale is seen to limit floc growth. We propose a new flocculation model with a variable fractal dimension that predicts the temporal evolution of the floc size and shape.
We present experimental data providing evidence for the formation of transient (${\sim }20\ \mathrm {\mu }\textrm {s}$) plasmas that are simultaneously weakly magnetized (i.e. Hall magnetization parameter $\omega \tau > 1$) and dominated by thermal pressure (i.e. ratio of thermal-to-magnetic pressure $\beta > 1$). Particle collisional mean free paths are an appreciable fraction of the overall system size. These plasmas are formed via the head-on merging of two plasmas launched by magnetized coaxial guns. The ratio $\lambda _{\textrm {gun}}=\mu _0 I_{\textrm {gun}}/\psi _{\textrm {gun}}$ of gun current $I_{\textrm {gun}}$ to applied magnetic flux $\psi _{\textrm {gun}}$ is an experimental knob for exploring the parameter space of $\beta$ and $\omega \tau$. These experiments were conducted on the Big Red Ball at the Wisconsin Plasma Physics Laboratory. The transient formation of such plasmas can potentially open up new regimes for the laboratory study of weakly collisional, magnetized, high-$\beta$ plasma physics; processes relevant to astrophysical objects and phenomena; and novel magnetized plasma targets for magneto-inertial fusion.
Although testing is widely regarded as critical to fighting the COVID-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics – population testing number and testing coverage – to population mortality outcomes and identify a benchmark for testing adequacy. We aggregated publicly available data through 12 April on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. We found that testing coverage, but not population testing number, was highly correlated with population mortality (rs = −0.79, P = 5.975 × 10−9vs. rs = −0.3, P = 0.05) and case fatality rate (rs = −0.67, P = 9.067 × 10−6vs. rs = −0.21, P = 0.20). A testing coverage threshold of 15–45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality; above 45, increased testing did not yield significant incremental mortality benefit. Taken together, testing coverage was better than population testing number in explaining country performance and can serve as an early and sensitive indicator of testing adequacy and disease burden.
We propose a one-way coupled model that tracks individual primary particles in a conceptually simple cellular flow set-up to predict flocculation in turbulence. This computationally efficient model accounts for Stokes drag, lubrication, cohesive and direct contact forces on the primary spherical particles, and allows for a systematic simulation campaign that yields the transient mean floc size as a function of the governing dimensionless parameters. The simulations reproduce the growth of the cohesive flocs with time, and the emergence of a log-normal equilibrium distribution governed by the balance of aggregation and breakage. Flocculation proceeds most rapidly when the Stokes number of the primary particles is $O(1)$. Results from this simple computational model are consistent with experimental observations, thus allowing us to propose a new analytical flocculation model that yields improved agreement with experimental data, especially during the transient stages.
Researchers have studied psychological disorders extensively from a common cause perspective, in which symptoms are treated as independent indicators of an underlying disease. In contrast, the causal systems perspective seeks to understand the importance of individual symptoms and symptom-to-symptom relationships. In the current study, we used network analysis to examine the relationships between and among depression and anxiety symptoms from the causal systems perspective.
Method
We utilized data from a large psychiatric sample at admission and discharge from a partial hospital program (N = 1029, mean treatment duration = 8 days). We investigated features of the depression/anxiety network including topology, network centrality, stability of the network at admission and discharge, as well as change in the network over the course of treatment.
Results
Individual symptoms of depression and anxiety were more related to other symptoms within each disorder than to symptoms between disorders. Sad mood and worry were among the most central symptoms in the network. The network structure was stable both at admission and between admission and discharge, although the overall strength of symptom relationships increased as symptom severity decreased over the course of treatment.
Conclusions
Examining depression and anxiety symptoms as dynamic systems may provide novel insights into the maintenance of these mental health problems.
Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes.
Method
Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted.
Results
Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN.
Conclusions
This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.
In this study, the fictitious time integration method (FTIM) is applied to investigate wave propagation over an arbitrary bathymetry with measured uncertainty. The FTIM is used to convert the higher-order elliptic mild-slope equation (EMSE) into a FTIM like EMSE (FTIMEMSE). It has the advantage to describe wave transformation from deep water to shallow water region in a large coastal area with numerical efficiency. The validity of the noise resistance for the measured uncertainty of the bathymetry is also studied. In addition, typical examples for waves propagating over an elliptic shoal rest on a horizontal and sloping bottom is presented. It is concluded that the FTIM is robust in the numerical stability and capable of against the noise of the measurement.
Surveillance is integral for the monitoring and control of infectious diseases. We conducted prospective laboratory surveillance of methicillin-resistant Staphylococcus aureus (MRSA) in five Singaporean public-sector hospitals from 2006 to 2010, using WHONET 5.6 for data compilation and analysis. Molecular profiling using multilocus variable-number tandem-repeat analysis, staphylococcal cassette chromosome mec classification and multilocus sequence typing was performed for a random selection of isolates. Our results showed overall stable rates of infection and bacteraemia, although there was significant variance among the individual hospitals, with MRSA rates increasing in two smaller hospitals and showing a trend towards decreasing in the two largest hospitals. The proportion of blood isolates that are EMRSA-15 (ST22-IV) continued to increase over time, slowly replacing the multi-resistant ST239-III. A new MRSA clone – ST45-IV – is now responsible for a small subset of hospital infections locally. More effort is required in Singaporean hospitals in order to reduce the rates of MRSA infection significantly.
In the past 15 years, stretchable electronic circuits have emerged as a new technology in the domain of assembly, interconnections, and sensor circuit technologies. In the meantime, a wide variety of processes using many different materials have been explored in this new field. In the current contribution, we present an approach inspired by conventional rigid and flexible printed circuit board (PCB) technology. Similar to PCBs, standard packaged, rigid components are assembled on copper contact pads using lead-free solder reflow processes. Stretchability is obtained by shaping the copper tracks as horseshoe-shaped meanders. Elastic materials, predominantly polydimethylsiloxanes, are used to embed the conductors and the components, thus serving as a circuit carrier. We describe mechanical modeling, aimed at optimizing the build-up toward maximum mechanical reliability of the structures. Details on the production process, reliability assessment, and a number of functional demonstrators are described.
This study was performed to determine the prevalence, distribution of specimen sources, and antimicrobial susceptibility of the Acinetobacter calcoaceticus–Acinetobacter baumannii (Acb) species complex in Singapore. One hundred and ninety-three non-replicate Acb species complex clinical isolates were collected from six hospitals over a 1-month period in 2006. Of these, 152 (78·7%) were identified as A. baumannii, 18 (9·3%) as ‘Acinetobacter pittii’ [genomic species (gen. sp.) 3], and 23 (11·9%) as ‘Acinetobacter nosocomialis’ (gen. sp. 13TU). Carbapenem resistance was highest in A. baumannii (72·4%), followed by A. pittii (38·9%), and A. nosocomialis (34·8%). Most carbapenem-resistant A. baumannii and A. nosocomialis possessed the blaOXA-23-like gene whereas carbapenem-resistant A. pittii possessed the blaOXA-58-like gene. Two imipenem-resistant strains (A. baumannii and A. pittii) had the blaIMP-like gene. Representatives of carbapenem-resistant A. baumannii were related to European clones I and II.
The previous monolithic active grating bender design met some basic design requirements. However, after a real grating (BM-AGM) had been fabricated and installed for testing, the results showed that the usable length is a mere 60 mm because of the higher-order term error in the surface profile. A method was thus derived to eliminate the higher-order term error by modifying the width of the bender substrate through finite-element method simulation, reducing the residual error from about 100 nm to 6 nm. Owing to the closure of the grating department of Zeiss, ruling the monolithic bender is no longer available and the design has to be modified to a composite-type bender with Si substrate. A prototype was fabricated and assembled to examine all the design situations. The surface roughness of the width-modified Si substrate is around 30 nm before assembly. The residual error after assembly and bending is less than 10 nm. It proves that the design is feasible. However, due to the manufacturing capacity of the vendor, a short-length substrate is required and the design has to be modified. The detailed design modification and testing results are presented in this paper.