Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

Comparison of effect of CTG + STan with CTG alone on emergency Cesarean section rate: STan Australian Randomized controlled Trial (START).

OBJECTIVE: To investigate whether use of ST analysis of the fetal electrocardiogram (STan) as an adjunct to continuous cardiotocography (CTG) reduces the rate of emergency Cesarean section (EmCS) compared with CTG alone. METHODS: This was a randomized controlled trial of patients with a singleton fetus in cephalic presentation at ≥ 36 weeks' gestation, requiring continuous electronic fetal monitoring during labor at a tertiary maternity hospital in Adelaide, Australia, between January 2018 and July 2021. Participants were randomized to undergo CTG + STan or CTG alone. The calculated sample size was 1818 participants. The primary outcome was EmCS. Secondary outcomes included metabolic acidosis, a composite adverse perinatal outcome, and other maternal and neonatal morbidity and safety outcomes. RESULTS: The present study enrolled 970 women, of whom 967 were included in the primary analysis. EmCS occurred in 107/482 (22.2%) deliveries in the CTG + STan arm and in 107/485 (22.1%) in the CTG arm (adjusted relative risk, 1.02 (95% CI, 0.81-1.27); P = 0.89). There was no difference in the rate of adverse maternal or neonatal outcomes between arms. CONCLUSIONS: The addition of STan as an adjunct to continuous CTG did not reduce the EmCS rate. The smaller-than-anticipated sample size meant that this study was underpowered to detect absolute differences of ≤ 5% and, therefore, this negative finding could be due to a Type-2 error. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The operation of an ionization chamber with depleted gas for radioactivity measurement: Calibration procedure and utilising normalized manufacturer's radionuclide factors.

At the National Metrology Institute of South Africa (NMISA) absolute activity measurements of γ-emitting radionuclides are maintained for longevity on a secondary standard ionization chamber. Because the ionization chamber has lower gas pressure than that normally produced by the manufacturer, this paper focuses attention on explaining a normalization scheme devised to allow NMISA to make use of the manufacturer's supplied radionuclide calibration factors when necessary. The applicability of the procedure is justified through analysis of some results from a comprehensive simulation of the chamber undertaken in an independent study. Comparisons of the derived normalized calibration factors against those obtained through measurement at NMISA are made for a variety of radionuclides.

Activity determination of 18F using liquid scintillation beta-efficiency extrapolation and non-extrapolation methods.

The absolute activity of 18F was determined using 4πß-γ liquid scintillation coincidence counting using beta-efficiency extrapolation. An ionization chamber factor was determined for use during a SIRTI comparison, for which results are presented. A non-extrapolation method based on a detection efficiency analysis was also employed using an adaptation of the double-phototube coincidence efficiency for a threshold above the second monopeak. Results and uncertainty budgets for the two methods are presented and discussed.

A unified local objective function for optimally selecting SNPs on arrays for agricultural genomics applications.

Over the years, ad-hoc procedures were used for designing SNP arrays, but the procedures and strategies varied considerably case by case. Recently, a multiple-objective, local optimization (MOLO) algorithm was proposed to select SNPs for SNP arrays, which maximizes the adjusted SNP information (E score) under multiple constraints, e.g. on MAF, uniformness of SNP locations (U score), the inclusion of obligatory SNPs and the number and size of gaps. In the MOLO, each chromosome is split into equally spaced segments and local optima are selected as the SNPs having the highest adjusted E score within each segment, conditional on the presence of obligatory SNPs. The computation of the adjusted E score, however, is empirical, and it does not scale well between the uniformness of SNP locations and SNP informativeness. In addition, the MOLO objective function does not accommodate the selection of uniformly distributed SNPs. In the present study, we proposed a unified local function for optimally selecting SNPs, as an amendment to the MOLO algorithm. This new local function takes scalable weights between the uniformness and informativeness of SNPs, which allows the selection of SNPs under varied scenarios. The results showed that the weighting between the U and the E scores led to a higher imputation concordance rate than the U score or E score alone. The results from the evaluation of six commercial bovine SNP chips further confirmed this conclusion.

Genome assembly and phylogenomic data analyses using plastid data: Contrasting species tree estimation methods.

Phylogenomics has become increasingly popular in recent years mostly due to the increased affordability of next generation sequencing techniques. Phylogenomics has sparked interest in multiple fields of research, including systematics, ecology, epidemiology, and even personalized medicine, agriculture and pharmacy. Despite this trend, it is usually difficult to learn and understand how the analyses were done, how the results were obtained, and most importantly, how to replicate the study. Here we present the data and all of the code utilized to perform phylogenomic inferences using plastome data: from raw data to extensive phylogenetic inference and accuracy assessment. The data presented here utilizes plastome sequences available on GenBank (accession numbers of 94 species are available below) and the code is also available at https://github.com/deisejpg/rosids. Gonçalves et al. is the research article associated with the data analyses presented here.

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START).

BACKGROUND: Cardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress. METHODS: This study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women's and Children's Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness. DISCUSSION: Approximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour. TRIAL REGISTRATION: ANZCTR, ACTRN1261800006268 . Registered on 19 January 2018.

Evaluation of genotyping concordance for commercial bovine SNP arrays using quality-assurance samples.

SNP arrays are widely used in genetic research and agricultural genomics applications, and the quality of SNP genotyping data is of paramount importance. In the present study, SNP genotyping concordance and discordance were evaluated for commercial bovine SNP arrays based on two types of quality assurance (QA) samples provided by Neogen GeneSeek. The genotyping discordance rates (GDRs) between chips were on average between 0.06% and 0.37% based on the QA type I data and between 0.05% and 0.15% based on the QA type II data. The average genotyping error rate (GER) pertaining to single SNP chips, based on the QA type II data, varied between 0.02% and 0.08% per SNP and between 0.01% and 0.06% per sample. These results indicate that genotyping concordance rate was high (i.e. from 99.63% to 99.99%). Nevertheless, mitochondrial and Y chromosome SNPs had considerably elevated GDRs and GERs compared to the SNPs on the 29 autosomes and X chromosome. The majority of genotyping errors resulted from single allotyping errors, which also included the opposite instances for allele 'dropout' (i.e. from AB to AA or BB). Simultaneous allotyping errors on both alleles (e.g. mistaking AA for BB or vice versa) were relatively rare. Finally, a list of SNPs with a GER greater than 1% is provided. Interpretation of association effects of these SNPs, for example in genome-wide association studies, needs to be taken with caution. The genotyping concordance information needs to be considered in the optimal design of future bovine SNP arrays.

Evaluating the effect of metronidazole plus amoxicillin-clavulanate versus amoxicillin-clavulanate alone in canine haemorrhagic diarrhoea: a randomised controlled trial in primary care practice.

OBJECTIVES: To investigate the benefit of supplementing amoxicillin-clavulanic acid therapy with metronidazole in dogs presenting to a primary care veterinary practice with severe haemorrhagic diarrhoea. MATERIALS AND METHODS: Prospective randomised blinded trial on dogs presenting with haemorrhagic diarrhoea of less than 3 days duration to a primary care veterinary hospital and also requiring intravenous fluid therapy. Cases were randomised to receive either metronidazole or saline, in addition to standard supportive therapy consisting of amoxicillin-clavulanic acid, intravenous fluid therapy, buprenorphine and omeprazole. Treatment efficacy was measured by duration of hospitalisation and daily scoring of disease severity. RESULTS: Thirty-four cases successfully completed the trial. There was no significant difference in hospitalisation time between treatment groups (mean for dogs receiving metronidazole was 29.6 hours and for controls was 26.3 hours) nor in daily clinical scores. CLINICAL SIGNIFICANCE: This study strongly suggests that addition of metronidazole is not an essential addition to amoxicillin-clavulanic acid therapy for treatment of severe cases of haemorrhagic diarrhoea in dogs.

Significance of buoyancy in turbulence closure for computational fluid dynamics modelling of ultraviolet disinfection in maturation ponds.

Buoyancy-driven turbulent dispersion in a maturation pond is studied using a combination of field measurements and computational fluid dynamics. Modelling flow in maturation ponds requires turbulent closure models because of the large physical size and the need to model on diurnal timescales. Simulation results are shown to be more sensitive to the inclusion of a buoyancy production term appearing in the turbulent transport equations than to the model choice. Comparisons with experimental thermal profiles show that without this term, thermal mixing is over-predicted. When including the term, stratification occurs but thermal mixing is under-predicted in the lower water column. In terms of pond performance, the effect of this term is to cause increased surface die-off of Escherichia coli during sunlight hours due to the generation of stratification. It is recommended that future modelling consider and implement this term.

Absolute standardizations of 99mTc and 57Co by 4π electron-gamma liquid scintillation coincidence counting for SIRTI and SIR comparisons.

The radionuclides 99mTc and 57Co were standardized via absolute liquid scintillation counting techniques. We provide the first technical report on the absolute standardization of 99mTc using 4π(LS)e-γ coincidence counting. The low detection efficiency of low-energy conversion electrons translates into a large efficiency extrapolation range. A simulation indicated that the γ-ray interacting with the liquid scintillator introduces curvature to the count rate vs. efficiency relationship, the approximation of the functional form used for extrapolation providing the main measurement uncertainty for 99mTc. A detection efficiency analysis for both radionuclides is presented. Results from the standardizations, and SIRTI and SIR comparison exercises are reported.

Clinical improvements following bilateral anterior capsulotomy in treatment-resistant depression.

BACKGROUND: The purpose of this study was to evaluate a programme of lesion surgery carried out on patients with treatment-resistant depression (TRD). METHOD: This was a retrospective study looking at clinical and psychometric data from 45 patients with TRD who had undergone bilateral stereotactic anterior capsulotomy surgery over a period of 15 years, with the approval of the Mental Health Act Commission (37 with unipolar depression and eight with bipolar disorder). The Beck Depression Inventory (BDI) before and after surgery was used as the primary outcome measure. The Montgomery-Asberg Depression Rating Scale was administered and cognitive aspects of executive and memory functions were also examined. We carried out a paired-samples t test on the outcome measures to determine any statistically significant change in the group as a consequence of surgery. RESULTS: Patients improved on the clinical measure of depression after surgery by -21.20 points on the BDI with a 52% change. There were no significant cognitive changes post-surgery. Six patients were followed up in 2013 by phone interview and reported a generally positive experience. No major surgical complications occurred. CONCLUSIONS: With the limitations of an uncontrolled, observational study, our data suggest that capsulotomy can be an effective treatment for otherwise TRD. Performance on neuropsychological tests did not deteriorate.

Evidence against solar influence on nuclear decay constants.

The hypothesis that proximity to the Sun causes variation of decay constants at permille level has been tested and disproved. Repeated activity measurements of mono-radionuclide sources were performed over periods from 200 days up to four decades at 14 laboratories across the globe. Residuals from the exponential nuclear decay curves were inspected for annual oscillations. Systematic deviations from a purely exponential decay curve differ from one data set to another and are attributable to instabilities in the instrumentation and measurement conditions. The most stable activity measurements of alpha, beta-minus, electron capture, and beta-plus decaying sources set an upper limit of 0.0006% to 0.008% to the amplitude of annual oscillations in the decay rate. Oscillations in phase with Earth's orbital distance to the Sun could not be observed within a 10-6 to 10-5 range of precision. There are also no apparent modulations over periods of weeks or months. Consequently, there is no indication of a natural impediment against sub-permille accuracy in half-life determinations, renormalisation of activity to a distant reference date, application of nuclear dating for archaeology, geo- and cosmochronology, nor in establishing the SI unit becquerel and seeking international equivalence of activity standards.

Activity determination of (59)Fe by 4π beta-gamma counting using liquid scintillation in the beta channel.

This paper reports on absolute activity measurements of iron-59 made at the National Metrology Institute of South Africa (NMISA) via 4π(LS)ß-γ coincidence counting. The exercise formed part of an Asia Pacific Metrology Program (APMP) regional key comparison. Source data were analysed by the extrapolation technique for a number of gamma-ray window settings. In addition, a feasibility study was undertaken on a second technique; a non-extrapolation method based on a detection efficiency analysis. The reported activity concentration of the (59)Fe solution was determined with a relative uncertainty of 0.28% (k=1), the uncertainty being due mainly to the rate vs. efficiency fitting process. The result from the non-extrapolation method was lower than that given by extrapolation by 0.33%, within two standard deviations. Possible reasons for the small discrepancy are discussed.

Cooperative sequential-adsorption model in two dimensions with experimental applications for ionic self-assembly of nanoparticles.

Self-assembly of nanoparticles is an important tool in nanotechnology, with numerous applications, including thin films, electronics, and drug delivery. We study the deposition of ionic nanoparticles on a glass substrate both experimentally and theoretically. Our theoretical model consists of a stochastic cooperative adsorption and evaporation process on a two-dimensional lattice. By exploring the relationship between the initial concentration of nanoparticles in the colloidal solution and the density of particles deposited on the substrate, we relate the deposition rate of our theoretical model to the concentration.

A data-driven algorithm integrating clinical and laboratory features for the diagnosis and prognosis of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a major source of neonatal morbidity and mortality. Since there is no specific diagnostic test or risk of progression model available for NEC, the diagnosis and outcome prediction of NEC is made on clinical grounds. The objective in this study was to develop and validate new NEC scoring systems for automated staging and prognostic forecasting. STUDY DESIGN: A six-center consortium of university based pediatric teaching hospitals prospectively collected data on infants under suspicion of having NEC over a 7-year period. A database comprised of 520 infants was utilized to develop the NEC diagnostic and prognostic models by dividing the entire dataset into training and testing cohorts of demographically matched subjects. Developed on the training cohort and validated on the blind testing cohort, our multivariate analyses led to NEC scoring metrics integrating clinical data. RESULTS: Machine learning using clinical and laboratory results at the time of clinical presentation led to two nec models: (1) an automated diagnostic classification scheme; (2) a dynamic prognostic method for risk-stratifying patients into low, intermediate and high NEC scores to determine the risk for disease progression. We submit that dynamic risk stratification of infants with NEC will assist clinicians in determining the need for additional diagnostic testing and guide potential therapies in a dynamic manner. ALGORITHM AVAILABILITY: http://translationalmedicine.stanford.edu/cgi-bin/NEC/index.pl and smartphone application upon request.

Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants.

OBJECTIVES: To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC). STUDY DESIGN: Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation. RESULTS: A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC. CONCLUSIONS: We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.

Standardization of Tc-99 by three liquid scintillation counting methods.

The NMISA participated in the international key comparison of the pure beta-emitter Technetium-99, CCRI(II)-K2.Tc-99. The comparison solution was standardized using three methods, namely the TDCR efficiency calculation method, the CIEMAT/NIST efficiency tracing method and the 4π(LS)ß-γ coincidence tracing method with Co-60 as tracer. Excellent agreement between results obtained with the three methods confirmed the applicability of the beta spectral shape given by the latest (2011) DDEP evaluation of Tc-99 decay data, rather than the earlier (2004) evaluation.