Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effects of the nitric acid concentrations on the etching process, structural and optical properties of porous zinc oxide thin films

The present study reports on the fabrication of porous zinc oxide by wet chemical etching. ZnO thin films were deposited via radio-frequency magnetron sputtering on p-type silicon with (111) preferred orientation. The etchants used in the present work were 0.1% and 1.0% nitric acid (HNO3) solutions. ZnO were etched at various times and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and photoluminescence (PL) spectroscopy to allow the examination of their structural and optical properties. The XRD results revealed that the intensity of ZnO(002) decreased when the thin films were etched in varying HNO3 concentrations over different periods of time. The above observation is attributed to the dissolution of the ZnO(002). The SEM images showed that the thickness of the ZnO layers decreased over the etching time, which resulted from the isotropic etching by the HNO3 solution. The PL emission intensity initially increased with increasing etching time. However, with further etching of the samples, the PL spectra showed a decreasing trend in intensity as a result of the decrease in the surface-to-volume ratio. All results lead to the conclusion that 1.0% HNO3 has the capability to change the ZnO surface significantly

Structural properties of zinc oxide thin films deposited on various substrates

In this work, the structural properties of radio frequency sputtering-grown zinc oxide (ZnO) thin films on sapphire (Al2O3), gallium arsenide (GaAs) and n-type silicon (Si) substrates were characterized. Scanning electron microscopy was employed to study the surface morphology of the samples. X-ray diffraction (XRD) measurements were also performed to obtain the structural information of the samples. The XRD results showed that the ZnO layers grown on different substrates have similar lattice constant (c) values, which were used to calculate the strain percentages of the ZnO thin films. The surface morphologies of the ZnO thin films indicated the formation of a granular surface when ZnO is deposited on n-type Si(100) and Si(111) substrates. Meanwhile, a leaf-like surface is obtained when ZnO is deposited on GaAs and Al2O3 substrates. The results showed that the ZnO thin film grown on n-type Si(100) has the best quality among all the samples

Characterizations of cupric oxide thin films on glass and silicon substrates by radio frequency magnetron sputtering

Cupric oxide (CuO) thin films were prepared on a glass and silicon (Si) substrates by radio frequency magnetron sputtering system. The structural, optical and electrical properties of CuO films were characterized by X-ray diffraction (XRD), atomic force microscopy (AFM), Fourier transform infrared spectrometer, ultra-violet visible spectrophotometer, respectively, four point probe techniques and Keithley 4200 semiconductor characterization system. The XRD result showed that single phase CuO thin films with monoclinic structure were obtained. AFM showed well organized nano-pillar morphology with root mean square surface roughness for CuO thin films on glass and Si substrates were 3.64 and 1.91 nm, respectively. Infrared reflectance spectra shown a single reflection peak which is corresponding to CuO optical phonon mode and it confirmed that only existence of CuO composition on both substrates. The optical direct band gap energy of the CuO film grown on glass substrate, which is calculated from the optical transmission measurement was 1.37 eV. Finally, it was found that the deposited CuO films are resistive and the palladium formed ohmic contact for CuO on glass and schottky contact for CuO on Si

Taiwan Aboriginals and Peoples of the Pacific-Asia Region: Multivariate Craniometric Comparisons.

RefereedStepwise discriminant function analysis and Mahalanobis’s generalized distance are applied to twenty-nine cranial measurements recorded in 2,531 male crania representing five Taiwan aboriginal cranial series and fifty prehistoric, modern, and near modern human groups. The Taiwan aboriginal cranial series include modern samples of Atayal, Bunun, Pazeh, Babuza, and archaeological human remains from the Shi San Hang site (ca 1800-500 BP). The comparative cranial series represent East Asia, Southeast Asia, Australia, New Guinea, island Melanesia, Polynesia, and Micronesia. The results of two separate analyses, one using five and the other using fifty-five groups, are presented. A relatively close connection between the Babuza, Pazeh, and Shi San Hang aboriginal cranial series is observed while the Atayal and Bunun series remain relatively well differentiated. Connections between Taiwan aboriginal groups and cranial series from Polynesia suggest that Taiwan’s aboriginal inhabitants may have been the ancestral source of these inhabitants of Remote Oceania. Similarly, these results suggest that the ultimate source of Taiwan’s prehistoric and modern aboriginal groups may be among the early inhabitants of eastern (Northeast or Southeast) Asia. The results of the present craniometric analysis are compared with other lines of evidence which have been used to examine the affinities and origins of Taiwan’s aboriginal peoples