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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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.
The hepatic rudiment appears at approximately day 18 of gestation in the human embryo. By day 25 it can be recognized as an endodermal diverticulum, which projects into the mesenchymal septum transversum. By day 30 the hepatic diverticulum enlarges and divides into the pars hepatica, cranially, and the pars cystica, caudally. The pars hepatica forms parenchymal liver components; the pars cystica differentiates into the gallbladder and cystic ducts (Figure 16.1). The gallbladder primordium is a solid structure that later in development becomes cystic, as found in the adult .
There is a growing consensus in the literature that governance architectures matter. However, we lack sufficient knowledge about their emergence, dynamics and impacts. This concluding chapter summarizes all insights in the book Architectures of Earth System Governance, and emphasizes how this book has made a scientific contribution by enhancing conceptual clarity, synthesizing a decade of intense research, and charting directions for future research. The book has made at least one point clear: the ‘architecture lens’ offers a bird’s-eye view on the global governance landscape that is highly valuable in explaining outcomes of world politics. The architectures matter in how institutions interact with others, how institutions are entangled with others in larger regime complexes and how institutions are affected by broader architectures that are more or less fragmented or polycentric. In this concluding chapter, we also illustrate how such key insights gained could inform a set of transformative policy proposals regarding the architecture of earth system governance.
Novel and more conventional boron carbides were combined with n-type silicon to make heterojunction diodes, with neutron capture signal at zero applied bias. The boron carbides were based on the cross linking of closo-1,2-dicarbadodecaborane (ortho-carborane; 1,2-B10C2H12), and cross linking based on the combination of closo-1,2-dicarbadodecaborane (ortho-carborane; 1,2- B10C2H12) and pyridine. In the latter devices, pyridine concentration was varied; samples with a closo-1,2-dicarbadodecaborane (ortho-carborane; 1,2- B10C2H12) to pyridine ratio of 1:1 (BC:Py1) and 1:3 (BC:Py3). The result is a nonvolatile robust p-type semiconductor of boron carbide (B10C2Hx):(C5NHx)y. The I(V) curves for the resulting heterojunction diodes exhibit strong rectification where the normalized reverse bias leakage currents are largely unperturbed with increasing pyridine inclusion. The devices are largely gamma insensitive and yet neutron voltaic properties of these boron carbides is demonstrated. The neutron capture generated pulses from these heterojunction diodes were obtained at zero bias voltage although without the characteristic signatures of complete charge collection from boron neutron capture generated electron-hole pair production. These results, nonetheless, suggest that modifications to boron carbide may result in better neutron voltaic materials with linking groups chosen from family of aromatic compounds that stretch between borazine (B3N3H6) and benzene that point the way to a whole family of future studies that may ultimately lead to boron carbides better suited to low power and low flux neutron detection.
Retinal ganglion cell (RGC) dendritic atrophy is an early feature of many forms of retinal degeneration, providing a challenge to RGC classification. The characterization of these changes is complicated by the possibility that selective labeling of any particular class can confound the estimation of dendritic remodeling. To address this issue we have developed a novel, robust, and quantitative RGC classification based on proximal dendritic features which are resistant to early degeneration. RGCs were labeled through the ballistic delivery of DiO and DiI coated tungsten particles to whole retinal explants of 20 adult Brown Norway rats. RGCs were grouped according to the Sun classification system. A comprehensive set of primary and secondary dendrite features were quantified and a new classification model derived using principal component (PCA) and discriminant analyses, to estimate the likelihood that a cell belonged to any given class. One-hundred and thirty one imaged RGCs were analyzed; according to the Sun classification, 24% (n = 31) were RGCA, 29% (n = 38) RGCB, 32% (n = 42) RGCC, and 15% (n = 20) RGCD. PCA gave a 3 component solution, separating RGCs based on descriptors of soma size and primary dendrite thickness, proximal dendritic field size and dendritic tree asymmetry. The new variables correctly classified 73.3% (n = 74) of RGCs from a training sample and 63.3% (n = 19) from a hold out sample indicating an effective model. Soma and proximal dendritic tree morphological features provide a useful surrogate measurement for the classification of RGCs in disease. While a definitive classification is not possible in every case, the technique provides a useful safeguard against sample bias where the normal criteria for cell classification may not be reliable.
Frank W. DiPaola, Pediatric Gastroenterology, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medial Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA,
James E. Heubi, Clinical Translational Research Center, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA
Child maltreatment is a reliable predictor of posttraumatic stress disorder (PTSD) symptoms. However, not all maltreated children develop PTSD symptoms, suggesting that additional mediating variables explain how certain maltreated children develop PTSD symptoms and others do not. The current study tested three potential mediators of the relationship between child maltreatment and subsequent PTSD symptoms: (a) respiratory sinus arrhythmia reactivity, (b) cortisol reactivity, and (c) experiential avoidance, or the unwillingness to experience painful private events, such as thoughts and memories. Maltreated (n = 51) and nonmaltreated groups (n = 59) completed a stressor paradigm, a measure of experiential avoidance, and a semistructured interview of PTSD symptoms. One year later, participants were readministered the PTSD symptoms interview. Results of a multiple mediator model showed the set of potential mediators mediated the relationship between child maltreatment and subsequent PTSD symptoms. However, experiential avoidance was the only significant, specific indirect effect, demonstrating that maltreated children avoiding painful private events after the abuse were more likely to develop a range of PTSD symptoms 1 year later. These results highlight the importance of experiential avoidance in the development of PTSD symptoms for maltreated children, and implications for secondary prevention and clinical intervention models are discussed.
We present the design, fabrication, and measurement of a 2-way modified Wilkinson divider constructed in a coplanar geometry exhibiting ultra wideband isolation, transmission, and port matching in the millimeter-wave frequency range. The proposed divider replaces the lumped resistor in the conventional Wilkinson divider with two quarter-wave length transmission lines, a phase inverter, and two 2Z0 resistors. Except for the three ports that are coplanar waveguides (CPWs), the main body of the divider uses coplanar striplines (CPS). The phase inverter is realized using a simple airbridge-based crossover which is compatible with a modern monolithic microwave integrated circuit process. The divider has a ring-like configuration fabricated on a 620 µm thick semi-insulating GaAs wafer using electron beam lithography (EBL) technology. Three-dimensional (3D) full-wave electromagnetic simulations have been carried out to optimize the design and investigate the possible effect of fabrication tolerance on the performance of the crossover and the divider. Two dividers working at center frequencies of 25 and 80 GHz have been designed, fabricated, and tested. They all show consistent performance in terms of bandwidth, isolation, and port matching. Experimental and simulation results are in excellent agreement.