The role of gap junctions in the excitability of the myometrial smooth muscle network

Dysfunction of the myometrium is a major contributor to preterm labour. The current limitations to effective management of preterm labour is in large part due to our, as yet, incomplete insight into the mechanisms that underlie uterine excitability. The uterus goes through a period of activation towards the end of pregnancy during which the myometrium develops the ability to deliver the baby. Gap junctions are among the most important molecular entities involved in this activation process. In this thesis, a mathematical model based on FitzHugh-Nagumo dynamics is used to study the role that gap junctions play in controlling the excitability of the myometrium. Spatial heterogeneity is introduced into the network through stochastic assignment of coupling strengths based on physiological statistics. It is demonstrated that heterogeneity amplifies the ability of a locally applied stimulus to generate global activity and that the ability of the stimulus to excite the network is strongly dependent on the local spatial correlation structure of the couplings. In networks driven by a pacemaker cell, large coupling strengths preclude activity by reducing the frequency of the stimulating oscillations. The model is extended to incorporate voltage-dependent gap junctions. It is established in the literature that gap-junctional conductance is dependent on the transjunctional voltage of neighbouring myocytes. Two conductance relationships have been observed corresponding to gap junctions composed of connexin-43 or connexin-45 proteins. It is demonstrated here that networks with only connexin-45 proteins are unable to exhibit global excitability whereas networks with connexin-43 proteins always display full activity. The mathematical models are supported by analysis of human and rat RNA expression data which shows that connexin-45 is down-regulated at term. It is hypothesised that connexin-45 blocks activity in the uterus throughout gestation, and is down-regulated at term to allow the uterus to deliver the powerful contractions associated with labour

Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium

The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability

Photometric Redshift Probability Distributions for Galaxies in the SDSS DR8

We present redshift probability distributions for galaxies in the SDSS DR8 imaging data. We used the nearest-neighbor weighting algorithm presented in Lima et al. 2008 and Cunha et al. 2009 to derive the ensemble redshift distribution N(z), and individual redshift probability distributions P(z) for galaxies with r < 21.8. As part of this technique, we calculated weights for a set of training galaxies with known redshifts such that their density distribution in five dimensional color-magnitude space was proportional to that of the photometry-only sample, producing a nearly fair sample in that space. We then estimated the ensemble N(z) of the photometric sample by constructing a weighted histogram of the training set redshifts. We derived P(z) s for individual objects using the same technique, but limiting to training set objects from the local color-magnitude space around each photometric object. Using the P(z) for each galaxy, rather than an ensemble N(z), can reduce the statistical error in measurements that depend on the redshifts of individual galaxies. The spectroscopic training sample is substantially larger than that used for the DR7 release, and the newly added PRIMUS catalog is now the most important training set used in this analysis by a wide margin. We expect the primary source of error in the N(z) reconstruction is sample variance: the training sets are drawn from relatively small volumes of space. Using simulations we estimated the uncertainty in N(z) at a given redshift is 10-15%. The uncertainty on calculations incorporating N(z) or P(z) depends on how they are used; we discuss the case of weak lensing measurements. The P(z) catalog is publicly available from the SDSS website.Comment: 29 pages, 9 figures, single colum

Cross-correlation Weak Lensing of SDSS Galaxy Clusters I: Measurements

This is the first in a series of papers on the weak lensing effect caused by clusters of galaxies in Sloan Digital Sky Survey. The photometrically selected cluster sample, known as MaxBCG, includes ~130,000 objects between redshift 0.1 and 0.3, ranging in size from small groups to massive clusters. We split the clusters into bins of richness and luminosity and stack the surface density contrast to produce mean radial profiles. The mean profiles are detected over a range of scales, from the inner halo (25 kpc/h) well into the surrounding large scale structure (30 Mpc/h), with a significance of 15 to 20 in each bin. The signal over this large range of scales is best interpreted in terms of the cluster-mass cross-correlation function. We pay careful attention to sources of systematic error, correcting for them where possible. The resulting signals are calibrated to the ~10% level, with the dominant remaining uncertainty being the redshift distribution of the background sources. We find that the profiles scale strongly with richness and luminosity. We find the signal within a given richness bin depends upon luminosity, suggesting that luminosity is more closely correlated with mass than galaxy counts. We split the samples by redshift but detect no significant evolution. The profiles are not well described by power laws. In a subsequent series of papers we invert the profiles to three-dimensional mass profiles, show that they are well fit by a halo model description, measure mass-to-light ratios and provide a cosmological interpretation.Comment: Paper I in a series; v2.0 includes ApJ referee's suggestion

Adult Social Work and High Risk Domestic Violence Cases

Summary This article focuses on adult social work’s response in England to high-risk domestic violence cases and the role of adult social workers in Multi-Agency Risk and Assessment Conferences. (MARACs). The research was undertaken between 2013-2014 and focused on one city in England and involved the research team attending MARACs, Interviews with 20 adult social workers, 24 MARAC attendees, 14 adult service users at time T1 (including follow up interviews after six months, T2), focus groups with IDVAs and Women’s Aid and an interview with a Women’s Aid service user. Findings The findings suggest that although adult social workers accept the need to be involved in domestic violence cases they are uncertain of what their role is and are confused with the need to operate a parallel domestic violence and adult safeguarding approach, which is further, complicated by issues of mental capacity. MARACS are identified as overburdened, under-represented meetings staffed by committed managers. However, they are in danger of becoming managerial processes neglecting the service users they are meant to protect. Applications The article argues for a re-engagement of adult social workers with domestic violence that has increasingly become over identified with child protection. It also raises the issue whether MARACS remain fit for purpose and whether they still represent the best possible response to multi-agency coordination and practice in domestic violence

Halo mass - concentration relation from weak lensing

We perform a statistical weak lensing analysis of dark matter profiles around tracers of halo mass from galactic- to cluster-size halos. In this analysis we use 170,640 isolated ~L* galaxies split into ellipticals and spirals, 38,236 groups traced by isolated spectroscopic Luminous Red Galaxies (LRGs) and 13,823 MaxBCG clusters from the Sloan Digital Sky Survey (SDSS) covering a wide range of richness. Together these three samples allow a determination of the density profiles of dark matter halos over three orders of magnitude in mass, from 10^{12} M_{sun} to 10^{15} M_{sun}. The resulting lensing signal is consistent with an NFW or Einasto profile on scales outside the central region. We find that the NFW concentration parameter c_{200b} decreases with halo mass, from around 10 for galactic halos to 4 for cluster halos. Assuming its dependence on halo mass in the form of c_{200b} = c_0 [M/(10^{14}M_{sun}/h)]^{\beta}, we find c_0=4.6 +/- 0.7 (at z=0.22) and \beta=0.13 +/- 0.07, with very similar results for the Einasto profile. The slope (\beta) is in agreement with theoretical predictions, while the amplitude is about two standard deviations below the predictions for this mass and redshift, but we note that the published values in the literature differ at a level of 10-20% and that for a proper comparison our analysis should be repeated in simulations. We discuss the implications of our results for the baryonic effects on the shear power spectrum: since these are expected to increase the halo concentration, the fact that we see no evidence of high concentrations on scales above 20% of the virial radius suggests that baryonic effects are limited to small scales, and are not a significant source of uncertainty for the current weak lensing measurements of the dark matter power spectrum. [ABRIDGED]Comment: 17 pages, 5 figures, accepted to JCAP pending minor revisions that are included in v2 here on arXi

The modENCODE Data Coordination Center: lessons in harvesting comprehensive experimental details.

The model organism Encyclopedia of DNA Elements (modENCODE) project is a National Human Genome Research Institute (NHGRI) initiative designed to characterize the genomes of Drosophila melanogaster and Caenorhabditis elegans. A Data Coordination Center (DCC) was created to collect, store and catalog modENCODE data. An effective DCC must gather, organize and provide all primary, interpreted and analyzed data, and ensure the community is supplied with the knowledge of the experimental conditions, protocols and verification checks used to generate each primary data set. We present here the design principles of the modENCODE DCC, and describe the ramifications of collecting thorough and deep metadata for describing experiments, including the use of a wiki for capturing protocol and reagent information, and the BIR-TAB specification for linking biological samples to experimental results. modENCODE data can be found at http://www.modencode.org

Trauma history and depression predict incomplete adherence to antiretroviral therapies in a low income country.

As antiretroviral therapy (ART) for HIV becomes increasingly available in low and middle income countries (LMICs), understanding reasons for lack of adherence is critical to stemming the tide of infections and improving health. Understanding the effect of psychosocial experiences and mental health symptomatology on ART adherence can help maximize the benefit of expanded ART programs by indicating types of services, which could be offered in combination with HIV care. The Coping with HIV/AIDS in Tanzania (CHAT) study is a longitudinal cohort study in the Kilimanjaro Region that included randomly selected HIV-infected (HIV+) participants from two local hospital-based HIV clinics and four free-standing voluntary HIV counselling and testing sites. Baseline data were collected in 2008 and 2009; this paper used data from 36 month follow-up interviews (N = 468). Regression analyses were used to predict factors associated with incomplete self-reported adherence to ART. INCOMPLETE ART ADHERENCE WAS SIGNIFICANTLY MORE LIKELY TO BE REPORTED AMONGST PARTICIPANTS WHO EXPERIENCED A GREATER NUMBER OF CHILDHOOD TRAUMATIC EVENTS: sexual abuse prior to puberty and the death in childhood of an immediate family member not from suicide or homicide were significantly more likely in the non-adherent group and other negative childhood events trended toward being more likely. Those with incomplete adherence had higher depressive symptom severity and post-traumatic stress disorder (PTSD). In multivariable analyses, childhood trauma, depression, and financial sacrifice remained associated with incomplete adherence.\ud This is the first study to examine the effect of childhood trauma, depression and PTSD on HIV medication adherence in a low income country facing a significant burden of HIV. Allocating spending on HIV/AIDS toward integrating mental health services with HIV care is essential to the creation of systems that enhance medication adherence and maximize the potential of expanded antiretroviral access to improve health and reduce new infections

GREAT3 results I: systematic errors in shear estimation and the impact of real galaxy morphology

We present first results from the third GRavitational lEnsing Accuracy Testing (GREAT3) challenge, the third in a sequence of challenges for testing methods of inferring weak gravitational lensing shear distortions from simulated galaxy images. GREAT3 was divided into experiments to test three specific questions, and included simulated space- and ground-based data with constant or cosmologically-varying shear fields. The simplest (control) experiment included parametric galaxies with a realistic distribution of signal-to-noise, size, and ellipticity, and a complex point spread function (PSF). The other experiments tested the additional impact of realistic galaxy morphology, multiple exposure imaging, and the uncertainty about a spatially-varying PSF; the last two questions will be explored in Paper II. The 24 participating teams competed to estimate lensing shears to within systematic error tolerances for upcoming Stage-IV dark energy surveys, making 1525 submissions overall. GREAT3 saw considerable variety and innovation in the types of methods applied. Several teams now meet or exceed the targets in many of the tests conducted (to within the statistical errors). We conclude that the presence of realistic galaxy morphology in simulations changes shear calibration biases by $\sim 1$ per cent for a wide range of methods. Other effects such as truncation biases due to finite galaxy postage stamps, and the impact of galaxy type as measured by the S\'{e}rsic index, are quantified for the first time. Our results generalize previous studies regarding sensitivities to galaxy size and signal-to-noise, and to PSF properties such as seeing and defocus. Almost all methods' results support the simple model in which additive shear biases depend linearly on PSF ellipticity.Comment: 32 pages + 15 pages of technical appendices; 28 figures; submitted to MNRAS; latest version has minor updates in presentation of 4 figures, no changes in content or conclusion

A robust lower limit on the amplitude of matter fluctuations in the universe from cluster abundance and weak lensing

Cluster abundance measurements are among the most sensitive probes of the amplitude of matter fluctuations in the universe, which in turn can help constrain other cosmological parameters, like the dark energy equation of state or neutrino mass. However, difficulties in calibrating the relation between the cluster observable and halo mass, and the lack of completeness information, make this technique particularly susceptible to systematic errors. Here we argue that a cluster abundance analysis using statistical weak lensing on the stacked clusters leads to a robust lower limit on the amplitude of fluctuations. The method compares the average weak lensing signal measured around the whole cluster sample to a theoretical prediction, assuming that the clusters occupy the centers of all of the most massive halos above some minimum mass threshold. If the amplitude of fluctuations is below a certain limiting value, there are too few massive clusters in this model and the theoretical prediction falls below the observations. Since any effects that modify the model assumptions can only decrease the theoretical prediction, the limiting amplitude becomes a robust lower limit. Here, we apply it to a volume limited sample of 16,000 group/cluster candidates identified from isolated luminous red galaxies (LRGs) in the Sloan Digital Sky Survey (SDSS). We find $\sigma_8 (\Omega_m/0.25)^{0.5}>0.62$ at the 95% c.l. after taking into account observational errors in the lensing analysis. While this is a relatively weak constraint, both the scatter in the LRG luminosity-halo mass relation and the lensing errors are large; the constraints could improve considerably in the future with more sophisticated cluster identification algorithms and smaller errors in the lensing analysis. [Abridged]Comment: 10 pages, 5 figures; new version has only very minor revisions to match published versio