In silico karyotyping of chromosomally polymorphic malaria mosquitoes in the Anopheles gambiae complex

Chromosomal inversion polymorphisms play an important role in adaptation to environmental heterogeneities. For mosquito species in the Anopheles gambiae complex that are significant vectors of human malaria, paracentric inversion polymorphisms are abundant and are associated with ecologically and epidemiologically important phenotypes. Improved understanding of these traits relies on determining mosquito karyotype, which currently depends upon laborious cytogenetic methods whose application is limited both by the requirement for specialized expertise and for properly preserved adult females at specific gonotrophic stages. To overcome this limitation, we developed sets of tag single nucleotide polymorphisms (SNPs) inside inversions whose biallelic genotype is strongly correlated with inversion genotype. We leveraged 1,347 fully sequenced An. gambiae and Anopheles coluzzii genomes in the Ag1000G database of natural variation. Beginning with principal components analysis (PCA) of population samples, applied to windows of the genome containing individual chromosomal rearrangements, we classified samples into three inversion genotypes, distinguishing homozygous inverted and homozygous uninverted groups by inclusion of the small subset of specimens in Ag1000G that are associated with cytogenetic metadata. We then assessed the correlation between candidate tag SNP genotypes and PCA-based inversion genotypes in our training sets, selecting those candidates with >80% agreement. Our initial tests both in held-back validation samples from Ag1000G and in data independent of Ag1000G suggest that when used for in silico inversion genotyping of sequenced mosquitoes, these tags perform better than traditional cytogenetics, even for specimens where only a small subset of the tag SNPs can be successfully ascertained

Analytic perturbation theory in QCD and Schwinger's connection between the beta-function and the spectral density

We argue that a technique called analytic perturbation theory leads to a well-defined method for analytically continuing the running coupling constant from the spacelike to the timelike region, which allows us to give a self-consistent definition of the running coupling constant for timelike momentum. The corresponding $\beta$-function is proportional to the spectral density, which confirms a hypothesis due to Schwinger.Comment: 11 pages, 2 figure

Linking Demographic Effects of Habitat Fragmentation Across Landscapes to Continental Source-Sink Dynamics

Forest fragmentation may cause increased brood parasitism and nest predation of breeding birds. In North America, nest parasitism and predation are expected to increase closer to forest edges because the brood-parasitic Brown-headed Cowbird(Molothrus ater) and generalist nest predators often enter the forest from adjoining developed (largely agricultural) habitats. Yet the abundance of brood parasites and nest predators at the patch scale may be strongly constrained by the total area of developed habitat at landscape scales. The scale and extent of landscape effects are unclear, however, because past studies were mostly conducted within local landscapes rather than across independent landscapes. We report replicated studies from 30 independent landscapes across 17 states of the United States that show that nest parasitism is strongly affected by fragmentation at a 20 km radius scale, equivalent to the maximum foraging range of cowbirds. Nest predation is influenced by both edge and landscape effects, and increases with fragmentation at a 10 km radius scale. Predation is additive to parasitism mortality, and the two together yield decreased population growth potential with increasing forest fragmentation at a 10 km radius scale for 20 of 22 bird species. Mapping of population growth potential across continental landscapes displays broad impacts of fragmentation on population viability and allows geographic prioritization for conservation

Capturing accelerometer outputs in healthy volunteers under normal and simulated-pathological conditions using ML classifiers

Wearable devices offer a possible solution for acquiring objective measurements of physical activity. Most current algorithms are derived using data from healthy volunteers. It is unclear whether such algorithms are suitable in specific clinical scenarios, such as when an individual has altered gait. We hypothesized that algorithms trained on healthy population will result in less accurate results when tested in individuals with altered gait. We further hypothesized that algorithms trained on simulated-pathological gait would prove better at classifying abnormal activity.We studied healthy volunteers to assess whether activity classification accuracy differed for those with healthy and simulated-pathological conditions. Healthy participants (n=30) were recruited from the University of Leeds to perform nine predefined activities under healthy and simulated-pathological conditions. Activities were captured using a wrist-worn MOX accelerometer (Maastricht Instruments, NL). Data were analyzed based on the Activity-Recognition-Chain process. We trained a Neural-Network, Random-Forests, k-Nearest-Neighbors (k-NN), Support-Vector-Machines (SVM) and Naive Bayes models to classify activity. Algorithms were trained four times; once with 'healthy' data, and once with 'simulated-pathological data' for each of activity-type and activity-task classification. In activity-type instances, the SVM provided the best results; the accuracy was 98.4% when the algorithm was trained and then tested with unseen data from the same group of healthy individuals. Accuracy dropped to 52.8% when tested on simulated-pathological data. When the model was retrained with simulated-pathological data, prediction accuracy for the corresponding test set was 96.7%. Algorithms developed on healthy data are less accurate for pathological conditions. When evaluating pathological conditions, classifier algorithms developed using data from a target sub-population can restore accuracy to above 95%.Clinical Relevance - This method remotely establishes health-related data of objective outcome measures of activities of daily living

A Multi-objective Exploratory Procedure for Regression Model Selection

Variable selection is recognized as one of the most critical steps in statistical modeling. The problems encountered in engineering and social sciences are commonly characterized by over-abundance of explanatory variables, non-linearities and unknown interdependencies between the regressors. An added difficulty is that the analysts may have little or no prior knowledge on the relative importance of the variables. To provide a robust method for model selection, this paper introduces the Multi-objective Genetic Algorithm for Variable Selection (MOGA-VS) that provides the user with an optimal set of regression models for a given data-set. The algorithm considers the regression problem as a two objective task, and explores the Pareto-optimal (best subset) models by preferring those models over the other which have less number of regression coefficients and better goodness of fit. The model exploration can be performed based on in-sample or generalization error minimization. The model selection is proposed to be performed in two steps. First, we generate the frontier of Pareto-optimal regression models by eliminating the dominated models without any user intervention. Second, a decision making process is executed which allows the user to choose the most preferred model using visualisations and simple metrics. The method has been evaluated on a recently published real dataset on Communities and Crime within United States.Comment: in Journal of Computational and Graphical Statistics, Vol. 24, Iss. 1, 201

Epidemic syphilis exhibits diverse manifestations

Copyright to Australian Family Physician. Reproduced with permission. Permission to reproduce must be sought from the publisher, The Royal Australian College of General Practitioners.There are recent reports of a sustained increase in the incidence of syphilis around the world, including in the Australian cities of Sydney and Melbourne. In Queensland, there has been both an increase in the number of notifications and also a change in the epidemiology of the disease. While syphilis was previously predominantly seen in indigenous men and women, it now mostly occurs in nonindigenous men who have sex with other men - although per capita, indigenous Queenslanders remain overrepresented. Efforts to improve screening and treatment have shortened the time from diagnosis to treatment and appear to have been successful in reducing the rates of disease in remote indigenous populations. These efforts have included the establishment of a state wide syphilis register and active encouragement to remote practitioners to offer testing to patients aged 15–39 years as a part of the annual adult health check. Adoption of single dose azithromycin for syndromic treatment of urethritis and cervicitis and their contacts, albeit at a dose of only 1 g, may be having an impact as well.Andrew M Redmond; Craig M Dancer; Andrew R Doolan; Diane F Rowling; Marion L Wood

Two-Loop Calculations with Vertex Corrections in the Walecka Model

Two-loop corrections with scalar and vector form factors are calculated for nuclear matter in the Walecka model. The on-shell form factors are derived from vertex corrections within the framework of the model and are highly damped at large spacelike momenta. The two-loop corrections are evaluated first by using the one-loop parameters and mean fields and then by refitting the total energy/baryon to empirical nuclear matter saturation properties. The modified two-loop corrections are significantly smaller than those computed with bare vertices. Contributions from the anomalous isoscalar form factor of the nucleon are included for the first time. The effects of the implicit density dependence of the form factors, which arise from the shift in the baryon mass, are also considered. Finally, necessary extensions of these calculations are discussed.Comment: 29 pages in REVTeX, 18 figures, preprint IU/NTC 94-02 //OSU--94-11

SOX9 transduction of a human chondrocytic cell line identifies novel genes regulated in primary human chondrocytes and in osteoarthritis

The transcription factor SOX9 is important in maintaining the chondrocyte phenotype. To identify novel genes regulated by SOX9 we investigated changes in gene expression by microarray analysis following retroviral transduction with SOX9 of a human chondrocytic cell line (SW1353). From the results the expression of a group of genes (SRPX, S100A1, APOD, RGC32, CRTL1, MYBPH, CRLF1 and SPINT1) was evaluated further in human articular chondrocytes (HACs). First, the same genes were investigated in primary cultures of HACs following SOX9 transduction, and four were found to be similarly regulated (SRPX, APOD, CRTL1 and S100A1). Second, during dedifferentiation of HACs by passage in monolayer cell culture, during which the expression of SOX9 progressively decreased, four of the genes (S100A1, RGC32, CRTL1 and SPINT1) also decreased in their expression. Third, in samples of osteoarthritic (OA) cartilage, which had decreased SOX9 expression compared with age-matched controls, there was decreased expression of SRPX, APOD, RGC32, CRTL1 and SPINT1. The results showed that a group of genes identified as being upregulated by SOX9 in the initial SW1353 screen were also regulated in expression in healthy and OA cartilage. Other genes initially identified were differently expressed in isolated OA chondrocytes and their expression was unrelated to changes in SOX9. The results thus identified some genes whose expression appeared to be linked to SOX9 expression in isolated chondrocytes and were also altered during cartilage degeneration in osteoarthritis

Twelve-month prevalence of haemarthrosis and joint disease using the Haemophilia Joint Health score: evaluation of the UK National Haemophilia Database and Haemtrack patient reported data: an observational study

Objectives: To report the 12-month prevalence of joint bleeds from the National Haemophilia Database (NHD) and Haemtrack, a patient-reported online treatment diary and concurrent joint disease status using the haemophilia joint health score (HJHS) at individual joint level, in children and adults with severe haemophilia A and B (HA/HB) without a current inhibitor. Design: A 2018 retrospective database study of NHD from which 2238 cases were identified, 463 patients had fully itemised HJHS of whom 273 were compliant in recording treatment using Haemtrack. Setting: England, Wales and Scotland, UK. Participants: Children (<18 years) and adults (≥18 years) with severe HA and HB (factor VIII/factor IX, <0.01 iu/mL) without a current inhibitor. Primary and secondary outcomes: Prevalence of joint haemarthrosis and concurrent joint health measured using the HJHS. Results: The median (IQR) age of children was 10 (6-13) and adults 40 (29-50) years. Haemarthrosis prevalence in HA/HB children was 33% and 47%, respectively, and 60% and 42%, respectively, in adults. The most common site of haemarthrosis in children was the knee in HA and ankle in HB. In adults, the incidence of haemarthrosis at the ankles and elbows was equal. The median total HJHS in HA/HB children was 0 and in adults with HA/HB, were 18 and 11, respectively. In adults with HA/HB, the median ankle HJHS of 4.0 was higher than the median HJHS of 1.0 for both the knee and elbow. Conclusion: Despite therapeutic advances, only two-thirds of children and one-third of adults were bleed-free, even in a UK cohort selected for high compliance with prophylaxis. The median HJHS of zero in children suggests joint health is relatively unaffected during childhood. In adults, bleed rates were highest in ankles and elbows, but the ankles led to substantially worse joint health scores

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up