Genetics University of Toronto Thrombophilia Study in Women (GUTTSI): genetic and other risk factors for venous thromboembolism in women

BACKGROUND: Women may be at increased risk for venous thromboembolism (VTE) as compared with men. We studied the effects of genetic and biochemical markers of thrombophilia in women, in conjunction with other established risk factors for VTE. METHOD: The present retrospective case-control study was conducted in a thrombosis treatment programme at a large Toronto hospital. The cases were 129 women aged 16-79 years with objectively confirmed VTE. Age-matched control individuals were women who were free of venous thrombosis. Neither cases nor control individuals had known cardiovascular disease. Participants were interviewed regarding personal risk factors for VTE, including smoking, history of malignancy, pregnancy, and oestrogen or oral contraceptive use. Blood specimens were analyzed for common single nucleotide polymorphisms of prothrombin, factor V and methylenetetrahydrofolate reductase (MTHFR; C677T, A1298C and T1317C), and the A66G polymorphism for methionine synthase reductase (MTRR).Fasting plasma homocysteine was also analyzed. RESULTS: Women with VTE were significantly more likely than female control individuals to carry the prothrombin polymorphism and the factor V polymorphism, or to have fasting hyperhomocysteinaemia. Homozygosity for the C677T MTHFR gene was not a significant risk factor for VTE, or were the A1298C or T1317C MTHFR homozygous variants. Also, the A66G MTRR homozygous state did not confer an increased risk for VTE. CONCLUSION: Prothrombin and factor V polymorphisms increased the risk for VTE in women, independent from other established risk factors. Although hyperhomocysteinaemia also heightens this risk, common polymorphisms in two genes that are responsible for homocysteine remethylation do not. These findings are consistent with previous studies that included both men and women

In situ correlation between microplastic and suspended particulate matter concentrations in river-estuary systems support proxies for satellite-derived estimates of microplastic flux

Rivers are key pathways for transporting microplastics from land to the oceans, yet microplastic flux estimates remain uncertain. Remote sensing allows repeated broad-scale measurements and can be used to extrapolate limited in situ observations. This study investigated the relationship between suspended particulate matter (SPM), a satellite-observable water quality parameter, and microplastic concentration in a partially mixed estuary (Tamar, UK). Microplastic concentrations ranged from 0.04 to 0.99 microplastics/m3, decreasing downstream. A significant correlation was found between SPM and microplastic concentration over two seasons. This relationship was used to compute a multiyear timeseries of proxy microplastic concentration from satellite imagery and produce estimates of annual proxy microplastic flux. This approach could be applied to investigate microplastic flux in other major rivers worldwide where such a relationship between microplastics and SPM exists. To apply this workflow elsewhere, the establishment of local SPM-to-microplastic relationships from in situ observations and local validation of remote sensing SPM algorithms are essential

Revisiting special relativity: A natural algebraic alternative to Minkowski spacetime

Minkowski famously introduced the concept of a space-time continuum in 1908, merging the three dimensions of space with an imaginary time dimension $i c t$, with the unit imaginary producing the correct spacetime distance $x^2 - c^2 t^2$, and the results of Einstein's then recently developed theory of special relativity, thus providing an explanation for Einstein's theory in terms of the structure of space and time. As an alternative to a planar Minkowski space-time of two space dimensions and one time dimension, we replace the unit imaginary $i = \sqrt{-1}$, with the Clifford bivector $\iota = e_1 e_2$ for the plane that also squares to minus one, but which can be included without the addition of an extra dimension, as it is an integral part of the real Cartesian plane with the orthonormal basis $e_1$ and $e_2$. We find that with this model of planar spacetime, using a two-dimensional Clifford multivector, the spacetime metric and the Lorentz transformations follow immediately as properties of the algebra. This also leads to momentum and energy being represented as components of a multivector and we give a new efficient derivation of Compton's scattering formula, and a simple formulation of Dirac's and Maxwell's equations. Based on the mathematical structure of the multivector, we produce a semi-classical model of massive particles, which can then be viewed as the origin of the Minkowski spacetime structure and thus a deeper explanation for relativistic effects. We also find a new perspective on the nature of time, which is now given a precise mathematical definition as the bivector of the plane.Comment: 29 pages, 2 figure

Identification of Termite Species and Subspecies of the Genus Zootermopsis Using Near-Infrared Reflectance Spectroscopy

Dampwood termites of the genus Zootermopsis (Isoptera: Termopsidae) are an abundant group of basal termites found in temperate forests of western North America. Three species are currently recognized in the genus and one of these species is subdivided into two subspecies. Although morphological and genetic characters are useful in differentiating among the three species and the two subspecies, respectively, only hydrocarbon analysis can enable differentiation both among the three species and the two subspecies. Due to the limitations of hydrocarbon analysis, such as the need for fresh specimens, alternative methods that could rapidly and accurately identify Zootermopsis would be useful. Using a partial least squares analysis of near-infrared spectra, each of the Zootermopsis species and subspecies were identified with greater than 95% and 80% accuracy, respectively. Neural network analysis of the near-infrared spectra successfully enabled the identification of the species and subspecies with greater than 99% accuracy. The inexpensive, reproducible, and rapid nature of near-infrared spectroscopy makes it a viable alternative to morphological, hydrocarbon, or genetic analysis for identifying Zootermopsis

Spontaneous and deliberate future thinking: A dual process account

© 2019 Springer Nature.This is the final published version of an article published in Psychological Research, licensed under a Creative Commons Attri-bution 4.0 International License. Available online at: https://doi.org/10.1007/s00426-019-01262-7.In this article, we address an apparent paradox in the literature on mental time travel and mind-wandering: How is it possible that future thinking is both constructive, yet often experienced as occurring spontaneously? We identify and describe two ‘routes’ whereby episodic future thoughts are brought to consciousness, with each of the ‘routes’ being associated with separable cognitive processes and functions. Voluntary future thinking relies on controlled, deliberate and slow cognitive processing. The other, termed involuntary or spontaneous future thinking, relies on automatic processes that allows ‘fully-fledged’ episodic future thoughts to freely come to mind, often triggered by internal or external cues. To unravel the paradox, we propose that the majority of spontaneous future thoughts are ‘pre-made’ (i.e., each spontaneous future thought is a re-iteration of a previously constructed future event), and therefore based on simple, well-understood, memory processes. We also propose that the pre-made hypothesis explains why spontaneous future thoughts occur rapidly, are similar to involuntary memories, and predominantly about upcoming tasks and goals. We also raise the possibility that spontaneous future thinking is the default mode of imagining the future. This dual process approach complements and extends standard theoretical approaches that emphasise constructive simulation, and outlines novel opportunities for researchers examining voluntary and spontaneous forms of future thinking.Peer reviewe

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Transcriptional profiling of eosinophil subsets in interleukin-5 transgenic mice

Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. IL-5 is a critical regulator of eosinophil development, controlling proliferation, differentiation, and maturation of the lineage. Mice that constitutively express IL-5 have in excess of 10-fold more eosinophils in the hematopoietic organs than their wild type (WT) counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in WT mice. In this study, we assessed transcription in myeloid progenitors, eosinophil precursors, and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilized these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend toward quiescence along the trajectory. Additionally, we found gene expression changes associated with constitutive IL-5 signaling in eosinophil progenitors, many of which were not observed in eosinophils

Patterns of childhood body mass index (BMI), overweight and obesity in South Asian and black participants in the English National child measurement programme: effect of applying BMI adjustments standardising for ethnic differences in BMI-body fatness associations.

BACKGROUND: The National Child Measurement Programme (NCMP) records weight and height and assesses overweight-obesity patterns in English children using body mass index (BMI), which tends to underestimate body fatness in South Asian children and overestimate body fatness in Black children of presumed African ethnicity. Using BMI adjustments to ensure that adjusted BMI was similarly related to body fatness in South Asian, Black and White children, we reassessed population overweight and obesity patterns in these ethnic groups in NCMP. METHODS: Analyses were based on 2012-2013 NCMP data in 582 899 children aged 4-5 years and 485 362 children aged 10-11 years. Standard centile-based approaches defined weight status in each age group before and after applying BMI adjustments for English South Asian and Black children derived from previous studies using the deuterium dilution method. FINDINGS: Among White children, overweight-obesity prevalences (boys, girls) were 23% and 21%, respectively, in 4-5 year olds and 33% and 30%, respectively, in 10-11 year olds. Before adjustment, South Asian children had lower overweight-obesity prevalences at 4-5 years (19%, 19%) and slightly higher prevalences at 10-11 years (42%, 34%), whereas Black children had higher overweight-obesity prevalences both at 4-5 years (31%, 29%) and 10-11 years (42%, 45%). Following adjustment, overweight-obesity prevalences were markedly higher in South Asian children both at 4-5 years (39%, 35%) and at 10-11 years (52%, 44%), whereas Black children had lower prevalences at 4-5 years (11%, 12%); at 10-11 years, prevalences were slightly lower in boys (32%) but higher in girls (35%). INTERPRETATION: BMI adjustments revealed extremely high overweight-obesity prevalences among South Asian children in England, which were not apparent in unadjusted data. In contrast, after adjustment, Black children had lower overweight-obesity prevalences except among older girls. FUNDING: British Heart Foundation, NIHR CLAHRC (South London), NIHR CLAHRC (North Thames)