Gravitational lensing models as probes of dark matter scenarios

Galaxy clusters are composed of dark matter and of baryons, divided between the stars (10% of the mass) and the hot intra-cluster medium (ICM, 90%). Gravitational lensing allows to directly probe the potential of galaxy clusters, as it is directly sensitive to all the massive components. As dark matter represents most of the mass of clusters, the understanding of its correlation with baryonic matter is key to comprehend both its nature and clusters’ physics. We present the lens models of galaxy clusters MACS J0242 and MACS J0949, using a combination of imaging data from HST and DES, and spectroscopic data from VLT/MUSE. We then introduce a general method to convert the gravitational potential obtained through strong lensing into an ICM density profile, in the case of relaxed clusters. With lensing models, we compare our predicted ICM density to XMM-Newton X-ray and ACT sub-millimetre surveys. We explain the discrepancies by the extreme sensibility of the the lens model to ICM conversion function. Optimising the lensing density parameters with the ICM observations confirms this explanation as both optimised parameter spaces largely overlap. Concluding to the success of this technique, we encode in our lensing software Lenstool the ICM optimisation. With the HFF data of cluster Abell S1063, we perform the joint ICM-strong lensing optimisation, with a large number of multiply-imaged systems and Chandra X-ray data. Assuming the ICM to trace the large-scale dark matter halo yields a good quality lens model, in agreement with the lensing-only and ICM-only optimisations

Patient Outcomes in Palliative Care - South Australia, July - December 2018

The Australian palliative care sector is a world leader in using routine clinical assessment information to guide patient centred care and measure patient and family outcomes. Providers of palliative care are commended for their commitment to excellence in delivering evidence-based, patient-centred care by using the routine Palliative Care Outcomes Collaboration (PCOC) assessment framework and contributing patient data toward national outcome measurement and benchmarking. PCOC acknowledges the dedication and willingness of clinicians to improve the care of patients, their families and caregivers. The information collected is not just data - it represents the real-life outcomes of over 40,000 Australians who die an expected death every year. While the focus of this report is on the most recent information relating to July to December 2018, results over the last three years are also presented to highlight achievements and improvement in outcomes. The most recent information corresponds to 23,333 patients, having 29,931 episodes of care and 70,135 palliative care phases from 127 services who provide palliative care in hospital / hospice or in the person\u27s home

A full reconstruction of two galaxy clusters intra-cluster medium with strong gravitational lensing

Whilst X-rays and Sunyaev–Zel’dovich observations allow to study the properties of the intra-cluster medium (ICM) of galaxy clusters, their gravitational potential may be constrained using strong gravitational lensing. Although being physically related, these two components are often described with different physical models. Here, we present a unified technique to derive the ICM properties from strong lensing for clusters in hydrostatic equilibrium. In order to derive this model, we present a new universal and self-similar polytropic temperature profile, which we fit using the X-COP sample of clusters. We subsequently derive an analytical model for the electron density, which we apply to strong lensing clusters MACS J0242.5-2132 and MACS J0949.8+1708. We confront the inferred ICM reconstructions to XMM-Newton and ACT observations. We contrast our analytical electron density reconstructions with the best canonical β-model. The ICM reconstructions obtained prove to be compatible with observations. However they appear to be very sensitive to various dark matter halo parameters constrained through strong lensing (such as the core radius), and to the halo scale radius (fixed in the lensing optimizations). With respect to the important baryonic effects, we make the sensitivity on the scale radius of the reconstruction an asset, and use the inferred potential to constrain the dark matter density profile using ICM observations. The technique here developed should allow to take a new, and more holistic path to constrain the content of galaxy clusters

A profile of patients receiving palliative care in Western Australia for January - June 2019

The Palliative Care Outcomes Collaboration (PCOC) is a national program that aims to improve the quality and outcomes of palliative care in Australia. This is achieved via a standardised clinical language that supports a national data collection. This report provides a high level profile of 4,181 patients who received palliative care in Western Australia during July to December 2018 and had their pain, symptom, family / carer and psychological / spiritual issues assessed as part of routine clinical care

Joint HST, VLT/MUSE and XMM-Newton observations to constrain the mass distribution of the two strong lensing galaxy clusters: MACS J0242.5-2132 & MACS J0949.8+1708

We present the strong lensing analysis of two galaxy clusters: MACS J0242.5-2132 (MACS J0242, $z=0.313$) and MACS J0949.8+1708 (MACS J0949, $z=0.383$). Their total matter distributions are constrained thanks to the powerful combination of observations with the Hubble Space Telescope and the MUSE instrument. Using these observations, we precisely measure the redshift of six multiple image systems in MACS J0242, and two in MACS J0949. We also include four multiple image systems in the latter cluster identified in HST imaging without MUSE redshift measurements. For each cluster, our best-fit mass model consists of a single cluster-scale halo, and 57 (170) galaxy-scale halos for MACS J0242 (MACS J0949). Multiple images positions are predicted with a $rms$ 0.39 arcsec and 0.15 arcsec for MACS J0242 and MACS J0949 models respectively. From these mass models, we derive aperture masses of $M(R<$200 kpc$) = 1.67_{-0.05}^{+0.03}\times 10^{14} M_{\odot}$, and $M(R<$200 kpc$) = 2.00_{-0.20}^{+0.05}\times 10^{14} M_{\odot}$. Combining our analysis with X-ray observations from the XMM-Newton Observatory, we show that MACS J0242 appears to be a relatively relaxed cluster, while conversely, MACS J0949 shows a relaxing post-merger state. At 200 kpc, X-ray observations suggest the hot gas fraction to be respectively $f_g = 0.115^{+0.003}_{-0.004}$ and $0.053^{+0.007}_{-0.006}$ for MACS J0242 and MACS J0949. MACS J0242 being relaxed, its density profile is very well fitted by a NFW distribution, in agreement with X-ray observations. Finally, the strong lensing analysis of MACS J0949 suggests a flat dark matter density distribution in the core, between 10 and 100 kpc. This appears consistent with X-ray observations.Comment: 20 pages, 11 figures, published in MNRA

A full reconstruction of two galaxy clusters intra-cluster medium with strong gravitational lensing

Whilst X-rays and Sunyaev-Zel'dovich observations allow to study the properties of the intra-cluster medium (ICM) of galaxy clusters, their gravitational potential may be constrained using strong gravitational lensing. Although being physically related, these two components are often described with different physical models. Here, we present a unified technique to derive the ICM properties from strong lensing for clusters in hydrostatic equilibrium. In order to derive this model, we present a new universal and self-similar polytropic temperature profile, which we fit using the X-COP sample of clusters. We subsequently derive an analytical model for the electron density, which we apply to strong lensing clusters MACS J0242.5-2132 and MACS J0949.8+1708. We confront the inferred ICM reconstructions to XMM-Newton and ACT observations. We contrast our analytical electron density reconstructions with the best canonical $\beta$-model. The ICM reconstructions obtained prove to be compatible with observations. However they appear to be very sensitive to various dark matter halo parameters constrained through strong lensing (such as the core radius), and to the halo scale radius (fixed in the lensing optimisations). With respect to the important baryonic effects, we make the sensitivity on the scale radius of the reconstruction an asset, and use the inferred potential to constrain the dark matter density profile using ICM observations. The technique here developed should allow to take a new, and more holistic path to constrain the content of galaxy clusters.Comment: 26 pages, 21 figures, submitted to MNRA

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P &lt; 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T&gt;C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P &lt; .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10−18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10−11). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10−12) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10−10). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation