Discrete element framework for modelling extracellular matrix, deformable cells and subcellular components

This paper presents a framework for modelling biological tissues based on discrete particles. Cell components (e.g. cell membranes, cell cytoskeleton, cell nucleus) and extracellular matrix (e.g. collagen) are represented using collections of particles. Simple particle to particle interaction laws are used to simulate and control complex physical interaction types (e.g. cell-cell adhesion via cadherins, integrin basement membrane attachment, cytoskeletal mechanical properties). Particles may be given the capacity to change their properties and behaviours in response to changes in the cellular microenvironment (e.g., in response to cell-cell signalling or mechanical loadings). Each particle is in effect an 'agent', meaning that the agent can sense local environmental information and respond according to pre-determined or stochastic events. The behaviour of the proposed framework is exemplified through several biological problems of ongoing interest. These examples illustrate how the modelling framework allows enormous flexibility for representing the mechanical behaviour of different tissues, and we argue this is a more intuitive approach than perhaps offered by traditional continuum methods. Because of this flexibility, we believe the discrete modelling framework provides an avenue for biologists and bioengineers to explore the behaviour of tissue systems in a computational laboratory

Health status of transgender people globally: A systematic review of research on disease burden and correlates

Background and objectives Transgender and gender diverse (trans) health research has grown rapidly, highlighting the need to characterize the scientific evidence base. We conducted a systematic review of peer-reviewed research on disease burden and correlates in trans adolescents and adults over a 20-month period to identify knowledge gaps and assess methodological characteristics including measurement of gender identity, community engagement, and study quality. Data sources, eligibility criteria, and synthesis methods We searched seven databases using terms related to (a) transgender populations and (b) health or disease. Eligible studies were in English, French, or Spanish and reported original quantitative data on mental health or substance use conditions, infectious diseases, or noncommunicable conditions in at least 25 trans individuals aged 15+. Quality assessment was performed in duplicate on a 10% sample of articles and findings were summarized using narrative synthesis. Results The 328 included studies were conducted in 45 countries, with most from North America (54%) and limited research from South Asia (3%), Sub-Saharan Africa (3%), and the Middle East and North Africa (2%). Most studies used cross-sectional designs (73%) and convenience sampling (65%). Only 30% of studies reported any form of community engagement. Mental health and substance use disorders were the most studied area (77% of studies) and non-communicable conditions the least (16%). Available data indicated that trans populations experience high disease burden with considerable heterogeneity within and across settings. Of 39 articles assessed for quality, 80% were rated as fair, 18% as poor, and 3% as good quality. Conclusions and implications Geographic, gender-specific, and topical gaps remain in trans health, but we found more research from African countries, with transmasculine people, and on non-communicable conditions than previous syntheses. Areas for growth in trans health research include community engagement, non-binary health, chronic and age-related conditions, and health determinants

Palaeontology, the biogeohistory of Victoria

The broad-scale distribution of fossils within Victoria is controlled by general global patterns in the biological evolution of life on Earth, the local development and environmental evolution of habitats, and the occurrence of geological processes conducive to the preservation of fossil floras and faunas. Early Palaeozoic fossils are mostly marine in origin because of the predominance of marine sedimentary rocks in Victoria and because life on land was not significant during most of this time interval. Middle Palaeozoic sequences have both terrestrial and marine fossil records. Within Victoria, marine rocks are only very minor components of strata deposited during the late Palaeozoic, so that few marine fossils are known from this time period. A similar situation existed during most of the Mesozoic except towards the end of this era when marine conditions began to prevail in the Bass Strait region. During long intervals in the Cainozoic, large areas of Victoria were flooded by shallow-marine seas, particularly in the southern basins of Bass Strait, as well as in the northwest of the State (Murray Basin). Cainozoic sediments contain an extraordinary range of animal and plant fossils. During the Quaternary, the landscape of Victoria became, and continues to be, dominated by continental environments including, at times, extensive freshwater lake systems. Fossil floras and faunas from sediments deposited in these lake systems and from other continental sediments, as well as from Quaternary sediments deposited in marginal marine environments, collectively record a history of rapid fluctuations in climate and sea level.<br /

Primary or secondary? A dichotomy of the strontium isotope anomalies in the Ediacaran carbonates of Saudi Arabia

Secular variation of 87Sr/86Sr in carbonate strata has been widely used in regional and global chemostratigraphic correlations. Typically, diagenesis results in higher 87Sr/86Sr signals relative to their primary composition due to the alteration by Rb-rich fluids and radiogenic decay of 87Rb to 87Sr. Surprisingly, 87Sr/86Sr values in the Ediacaran limestones from Saudi Arabia (from 0.7029 to 0.7059) are significantly lower than typical Ediacaran seawater values (mostly from 0.7080 to 0.7090) based on a global compilation. Understanding the origin of these anomalies is important insofar as early macrofossils are preserved in these strata. Two hypotheses have been independently evaluated in this study. The first hypothesis shows a low temperature scenario with isolated oceans or lakes in proximity to a mafic source. The second hypothesis is characterized by a high temperature scenario with profound overprints by juvenile hydrothermal fluids. Integrated Sr and Nd isotope data reveal that the 87Sr/86Sr anomalies are closely coupled with positive εNd(t = 560 Ma) values (up to +4.1). Clear covariations between 87Sr/86Sr, εNd, TOC, δ13Ccarb, δ13Corg, and δ18Ocarb were found. Based on multiple lines of petrographic, field, and geochemical evidence, the second hypothesis (i.e., hydrothermal alteration by juvenile fluids) is preferred in this study. Thermogenic breakdown of organic matter in host sediments may have caused the increasingly low TOC abundance and high δ13Corg signals of the residual organic matter. We argue that the concept that the Ediacaran biotic radiation took place in an isolated lake environment should be treated with caution. These remarkably low 87Sr/86Sr signals have neither temporal nor biogeochemical significance. Sr isotope chemostratigraphy in this particular region may not be a reliable tool for stratigraphic correlations

Neutralino Dark Matter, b-tau Yukawa Unification and Non-Universal Sfermion Masses

We study the implications of minimal non-Universal Boundary Conditions in the sfermion Soft SUSY Breaking (SSB) masses of mSUGRA. We impose asymptotic b-tau Yukawa coupling Unification and we resort to a parameterization of the deviation from Universality in the SSB motivated by the multiplet structure of SU(5) GUT. A set of cosmo-phenomenological constraints, including the recent results from WMAP, determines the allowed parameter space of the models under consideration. We highlight a new coannihilation corridor where neutralino-sbottom and neutralino-tau sneutrino-stau coannihilations significantly contribute to the reduction of the neutralino relic density.Comment: 38 pages, 27 Figures, Latex; Version accepted for publication in PR

Young and Intermediate-age Distance Indicators

Distance measurements beyond geometrical and semi-geometrical methods, rely mainly on standard candles. As the name suggests, these objects have known luminosities by virtue of their intrinsic proprieties and play a major role in our understanding of modern cosmology. The main caveats associated with standard candles are their absolute calibration, contamination of the sample from other sources and systematic uncertainties. The absolute calibration mainly depends on their chemical composition and age. To understand the impact of these effects on the distance scale, it is essential to develop methods based on different sample of standard candles. Here we review the fundamental properties of young and intermediate-age distance indicators such as Cepheids, Mira variables and Red Clump stars and the recent developments in their application as distance indicators.Comment: Review article, 63 pages (28 figures), Accepted for publication in Space Science Reviews (Chapter 3 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Toward an internally consistent astronomical distance scale

Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Longitudinal HIV care outcomes by gender identity in the United States

Objective: Describe engagement in HIV care over time after initial engagement in HIV care, by gender identity.Design:Observational, clinical cohort study of people with HIV engaged in routine HIV care across the United States. Methods: We followed people with HIV who linked to and engaged in clinical care (attending ≥2 visits in 12 months) in cohorts in the North American Transgender Cohort Collaboration, 2000-2018. Within strata of gender identity, we estimated the 7-year (84-month) restricted mean time spent: lost-to-clinic (stratified by pre/postantiretroviral therapy (ART) initiation); in care prior to ART initiation; on ART but not virally suppressed; virally suppressed (≤200 copies/ml); or dead (pre/post-ART initiation). Results: Transgender women (N = 482/101 841) spent an average of 35.5 out of 84 months virally suppressed (this was 30.5 months for cisgender women and 34.4 months for cisgender men). After adjustment for age, race, ethnicity, history of injection drug use, cohort, and calendar year, transgender women were significantly less likely to die than cisgender people. Cisgender women spent more time in care not yet on ART, and less time on ART and virally suppressed, but were less likely to die compared with cisgender men. Other differences were not clinically meaningful. Conclusions: In this sample, transgender women and cisgender people spent similar amounts of time in care and virally suppressed. Additional efforts to improve retention in care and viral suppression are needed for all people with HIV, regardless of gender identity

Mass Bounds on a Very Light Neutralino

Within the Minimal Supersymmetric Standard Model (MSSM) we systematically investigate the bounds on the mass of the lightest neutralino. We allow for non-universal gaugino masses and thus even consider massless neutralinos, while assuming in general that R-parity is conserved. Our main focus are laboratory constraints. We consider collider data, precision observables, and also rare meson decays to very light neutralinos. We then discuss the astrophysical and cosmological implications. We find that a massless neutralino is allowed by all existing experimental data and astrophysical and cosmological observations.Comment: 36 pages, 13 figures, minor modification in astro-physical bounds. EPJC versio