The Dark Matter Telescope

Weak gravitational lensing enables direct reconstruction of dark matter maps over cosmologically significant volumes. This research is currently telescope-limited. The Dark Matter Telescope (DMT) is a proposed 8.4 m telescope with a 3 degree field of view, with an etendue of 260 $(m. degree)^2$, ten times greater than any other current or planned telescope. With its large etendue and dedicated observational mode, the DMT fills a nearly unexplored region of parameter space and enables projects that would take decades on current facilities. The DMT will be able to reach 10-sigma limiting magnitudes of 27-28 magnitude in the wavelength range .3 - 1 um over a 7 square degree field in 3 nights of dark time. Here we review its unique weak lensing cosmology capabilities and the design that enables those capabilities.Comment: in-press version with additions; to appear in proceedings of the Dark Matter 2000 conference (Santa Monica, February 2000) to be published by Springe

Foot Bone in Vivo: Its Center of Mass and Centroid of Shape

This paper studies foot bone geometrical shape and its mass distribution and establishes an assessment method of bone strength. Using spiral CT scanning, with an accuracy of sub-millimeter, we analyze the data of 384 pieces of foot bones in vivo and investigate the relationship between the bone's external shape and internal structure. This analysis is explored on the bases of the bone's center of mass and its centroid of shape. We observe the phenomenon of superposition of center of mass and centroid of shape fairly precisely, indicating a possible appearance of biomechanical organism. We investigate two aspects of the geometrical shape, (i) distance between compact bone's centroid of shape and that of the bone and (ii) the mean radius of the same density bone issue relative to the bone's centroid of shape. These quantities are used to interpret the influence of different physical exercises imposed on bone strength, thereby contributing to an alternate assessment technique to bone strength.Comment: 9 pages, 4 figure

Altered SMRT levels disrupt vitamin D3 receptor signalling in prostate cancer cells.

We hypothesized that key antiproliferative target genes for the vitamin D receptor (VDR) were repressed by an epigenetic mechanism in prostate cancer cells resulting in apparent hormonal insensitivity. To explore this possibility, we examined nuclear receptor corepressor expression in a panel of nonmalignant and malignant cell lines and primary cultures, and found frequently elevated SMRT corepressor mRNA expression often associated with reduced sensitivity to 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)2D3). For example, PC-3 and DU-145 prostate cancer cell lines had 1.8-fold and twofold increases in SMRT mRNA relative to normal PrEC cells (P<0.05). Similarly, 10/15 primary tumour cultures (including three matched to normal cells from the same donors) had elevated SMRT mRNA levels; generally NCoR1 and Alien were not as commonly elevated. Corepressor proteins often have associated histone deacetylases (HDAC) and reflectively the antiproliferative action of 1alpha,25(OH)2D3 can be restored by cotreatment with low doses of HDAC inhibitors such as trichostatin A (TSA, 15 nM) to induce apoptosis in prostate cancer cell lines. To decipher the transcriptional events that lead to these cellular responses, we undertook gene expression studies in PC-3 cells after cotreatment of 1alpha,25(OH)2D3 plus TSA after 6 h. Examination of known VDR target genes and cDNA microarray analyses revealed cotreatment of 1alpha,25(OH)2D3 plus TSA cooperatively upregulated eight (out of 1176) genes, including MAPK-APK2 and GADD45alpha. MRNA and protein time courses and inhibitor studies confirmed these patterns of regulation. Subsequently, we knocked down SMRT levels in PC-3 cells using a small interfering RNA (siRNA) approach and found that GADD45alpha induction by 1alpha,25(OH)2D3 alone became very significantly enhanced. The same distortion of gene responsiveness, with repressed induction of GADD45alpha was found in primary tumour cultures compared and to matched peripheral zone (normal) cultures from the same donor. These data demonstrate that elevated SMRT levels are common in prostate cancer cells, resulting in suppression of target genes associated with antiproliferative action and apparent 1alpha,25(OH)2D3-insensitivity. This can be targeted therapeutically by combination treatments with HDAC inhibitors

A coherent middle Pliocene magnetostratigraphy, Wanganui Basin, New Zealand

We document magnetostratigraphies for three river sections (Turakina, Rangitikei, Wanganui) in Wanganui Basin and interpret them as corresponding to the Upper Gilbert, the Gauss and lower Matuyama Chrons of the Geomagnetic Polarity Timescale, in agreement with foraminiferal biostratigraphic datums. The Gauss-Gilbert transition (3.58 Ma) is located in both the Turakina and Wanganui River sections, while the Gauss-Matuyama transition (2.58 Ma) is located in all three sections, as are the lower and upper boundaries of the Mammoth (3.33–3.22 Ma) and Kaena (3.11–3.04 Ma) Subchrons. Our interpretations are based in part on the re-analysis of existing datasets and in part on the acquisition and analysis of new data, particularly for the Wanganui River section. The palaeomagnetic dates of these six horizons provide the only numerical age control for a thick (up to 2000 m) mudstone succession (Tangahoe Mudstone) that accumulated chiefly in upper bathyal and outer neritic palaeoenvironments. In the Wanganui River section the mean sediment accumulation rate is estimated to have been about 1.8 m/k.y., in the Turakina section it was about 1.5 m/k.y., and in the Rangitikei section, the mean rate from the beginning of the Mammoth Subchron to the Hautawa Shellbed was about 1.1 m/k.y. The high rates may be associated with the progradation of slope clinoforms northward through the basin. This new palaeomagnetic timescale allows revised correlations to be made between cyclothems in the Rangitikei River section and the global Oxygen Isotope Stages (OIS) as represented in Ocean Drilling Program (ODP) Site 846. The 16 depositional sequences between the end of the Mammoth Subchron and the Gauss-Matuyama Boundary are correlated with OIS MG2 to 100. The cyclothems average 39 k.y. in duration in our age model, which is close to the 41 k.y. duration of the orbital obliquity cycles. We support the arguments advanced recently in defence of the need for local New Zealand stages as a means of classifying New Zealand sedimentary successions, and strongly oppose the proposal to move stage boundaries to selected geomagnetic polarity transitions. The primary magnetisation of New Zealand mudstone is frequently overprinted with secondary components of diagenetic origin, and hence it is often difficult to obtain reliable magnetostratigraphic records. We suggest specific approaches, analytical methods, and criteria to help ensure robustness and coherency in the palaeomagnetic identification of chron boundaries in typical New Zealand Cenozoic mudstone successions

Heritability of Lumbar Trabecular Bone Mechanical Properties in Baboons

Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h2) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h2 = 0.58), toughness (h2 = 0.64), and BV/TV (h2 = 0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures

Exploring the relationship between volunteering and hospice sustainability in the UK:A theoretical model

Aim: To explore the relationship between volunteering and the sustainability of UK voluntary hospices.Methods: A narrative literature review was conducted to inform the development of a theoretical model. Eight databases were searched: CINAHL (EBSCO), British Nursing Index, Intute: Health and Life Sciences, ERIC, SCOPUS, ASSIA (CSA), Cochrane Library and Google Scholar.Results: A total of 90 documents were analysed. Emerging themes included the importance of volunteering to the hospice economy and workforce, the quality of services, and public and community support. Findings suggest that hospice sustainability is dependent on volunteers; however, the supply and retention of volunteers is affected by internal and external factors.Conclusions: A theoretical model was developed to illustrate the relationship between volunteering and hospice sustainability. It demonstrates the factors necessary for hospice sustainability and the reciprocal impact that these factors and volunteering have on each other. The model has a practical application as an assessment framework and strategic planning tool

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales

England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000–62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch

Social disorganization and history of child sexual abuse against girls in sub-Saharan Africa : a multilevel analysis

Background: Child sexual abuse (CSA) is a considerable public health problem. Less focus has been paid to the role of community level factors associated with CSA. The aim of this study was to examine the association between neighbourhood-level measures of social disorganization and CSA. Methods: We applied multiple multilevel logistic regression analysis on Demographic and Health Survey data for 6,351 adolescents from six countries in sub-Saharan Africa between 2006 and 2008. Results: The percentage of adolescents that had experienced CSA ranged from 1.04% to 5.84%. There was a significant variation in the odds of reporting CSA across the communities, suggesting 18% of the variation in CSA could be attributed to community level factors. Respondents currently employed were more likely to have reported CSA than those who were unemployed (odds ratio [OR] = 2.05, 95% confidence interval [CI] 1.48 to 2.83). Respondents from communities with a high family disruption rate were 57% more likely to have reported CSA (OR=1.57, 95% CI 1.14 to 2.16). Conclusion: We found that exposure to CSA was associated with high community level of family disruption, thus suggesting that neighbourhoods may indeed have significant important effects on exposure to CSA. Further studies are needed to explore pathways that connect the individual and neighbourhood levels, that is, means through which deleterious neighbourhood effects are transmitted to individuals

An Exploration of Fetish Social Networks and Communities

Online Social Networks (OSNs) provide a venue for virtual interactions and relationships between individuals. In some communities, OSNs also facilitate arranging offline meetings and relationships. FetLife, the world’s largest anonymous social network for the BDSM, fetish and kink communities, provides a unique example of an OSN that serves as an interaction space, community organizing tool, and sexual market. In this paper, we present a first look at the characteristics of European members of Fetlife, comprising 504,416 individual nodes with 1,912,196 connections. We looked at user characteristics in terms of gender, sexual orientation, and preferred role. We further examined the homophilic communities and find that women in particular are far more platonically involved on the site than straight males. Our results suggest there are important differences between the FetLife community and conventional OSNs