Astrophysical limitations to the identification of dark matter: indirect neutrino signals vis-a-vis direct detection recoil rates

A convincing identification of dark matter (DM) particles can probably be achieved only through a combined analysis of different detections strategies, which provides an effective way of removing degeneracies in the parameter space of DM models. In practice, however, this program is made complicated by the fact that different strategies depend on different physical quantities, or on the same quantities but in a different way, making the treatment of systematic errors rather tricky. We discuss here the uncertainties on the recoil rate in direct detection experiments and on the muon rate induced by neutrinos from dark matter annihilations in the Sun, and we show that, contrarily to the local DM density or overall cross section scale, irreducible astrophysical uncertainties affect the two rates in a different fashion, therefore limiting our ability to reconstruct the parameters of the dark matter particle. By varying within their respective errors astrophysical parameters such as the escape velocity and the velocity dispersion of dark matter particles, we show that the uncertainty on the relative strength of the neutrino and direct-detection signal is as large as a factor of two for typical values of the parameters, but can be even larger in some circumstances.Comment: 12 pages, 3 figures. Improved presentation and Fig.3; clarifications, references and an appendix added; conclusions unchanged. Matches version published in PR

WIMP astronomy and particle physics with liquid-noble and cryogenic direct-detection experiments

Once weakly-interacting massive particles (WIMPs) are unambiguously detected in direct-detection experiments, the challenge will be to determine what one may infer from the data. Here, I examine the prospects for reconstructing the local speed distribution of WIMPs in addition to WIMP particle-physics properties (mass, cross sections) from next-generation cryogenic and liquid-noble direct-detection experiments. I find that the common method of fixing the form of the velocity distribution when estimating constraints on WIMP mass and cross sections means losing out on the information on the speed distribution contained in the data and may lead to biases in the inferred values of the particle-physics parameters. I show that using a more general, empirical form of the speed distribution can lead to good constraints on the speed distribution. Moreover, one can use Bayesian model-selection criteria to determine if a theoretically-inspired functional form for the speed distribution (such as a Maxwell-Boltzmann distribution) fits better than an empirical model. The shape of the degeneracy between WIMP mass and cross sections and their offset from the true values of those parameters depends on the hypothesis for the speed distribution, which has significant implications for consistency checks between direct-detection and collider data. In addition, I find that the uncertainties on theoretical parameters depends sensitively on the upper end of the energy range used for WIMP searches. Better constraints on the WIMP particle-physics parameters and speed distribution are obtained if the WIMP search is extended to higher energy (~ 1 MeV).Comment: 25 pages, 27 figures, matches published versio

Dark matter in the solar system III: The distribution function of WIMPs at the Earth from gravitational capture

In this last paper in a series of three on weakly interacting massive particle (WIMP) dark matter in the solar system, we focus on WIMPs bound to the system by gravitationally scattering off of planets. We present simulations of WIMP orbits in a toy solar system consisting of only the Sun and Jupiter. As previous work suggested, we find that the density of gravitationally captured WIMPs at the Earth is small and largely insensitive to the details of elastic scattering in the Sun. However, we find that the density of gravitationally captured WIMPs may be affected by external Galactic gravitational fields. If such fields are unimportant, the density of gravitationally captured WIMPs at the Earth should be similar to the maximum density of WIMPs captured in the solar system by elastic scattering in the Sun. Using standard assumptions about the halo WIMP distribution function, we find that the gravitationally captured WIMPs contribute negligibly to direct detection event rates. While these WIMPs do dominate the annihilation rate of WIMPs in the Earth, the resulting event rate in neutrino telescopes is too low to be observed in next-generation neutrino telescopes.Comment: 24 pages, 11 figures, to be submitte

Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia

A white paper resulting from the outcomes of the Osteoporosis Australia Summit, 20 October 2011 Abstract Osteoporosis imposes a tremendous burden on Australia: 1.2 million Australians have osteoporosis and 6.3 million have osteopenia. In the 2007–08 financial year, 82 000 Australians suffered fragility fractures, of which > 17 000 were hip fractures. In the 2000–01 financial year, direct costs were estimated at $1.9 billion per year and an additional$5.6 billion on indirect costs. Osteoporosis was designated a National Health Priority Area in 2002; however, implementation of national plans has not yet matched the rhetoric in terms of urgency. Building healthy bones throughout life, the Osteoporosis Australia strategy to prevent osteoporosis throughout the life cycle, presents an evidence-informed set of recommendations for consumers, health care professionals and policymakers. The strategy was adopted by consensus at the Osteoporosis Australia Summit in Sydney, 20 October 2011. Primary objectives throughout the life cycle are: to maximise peak bone mass during childhood and adolescence to prevent premature bone loss and improve or maintain muscle mass, strength and functional capacity in healthy adults to prevent and treat osteoporosis in order to minimise the risk of suffering fragility fractures, and reduce falls risk, in older people. The recommendations focus on three affordable and important interventions — to ensure people have adequate calcium intake, vitamin D levels and appropriate physical activity throughout their lives. Recommendations relevant to all stages of life include: daily dietary calcium intakes should be consistent with Australian and New Zealand guidelines serum levels of vitamin D in the general population should be above 50nmol/L in winter or early spring for optimal bone health regular weight-bearing physical activity, muscle strengthening exercises and challenging balance/mobility activities should be conducted in a safe environment

The Putative Role of Resveratrol in SIRT-1 Mediated Modulation of the Vitamin D Pathway

The nuclear vitamin D receptor (VDR) modulates gene transcription in 1,25-dihydroxyvitamin D (1,25D) target tissues such as kidney, colon, and bone. The 1,25D hormone is derived from vitamin D in the skin or from the diet, and binds to and activates the VDR. We have previously shown that resveratrol, an antioxidant found in the skin of red grapes, has the ability to activate the VDR signaling pathway. Moreover, cells treated with both resveratrol and 1,25D resulted in an additive or even synergistic stimulation of VDR-mediated transcription compared to cells treated with 1,25D alone. Based on these initial results, experiments were designed to test the significance of mutations in the hormone-binding domain of VDR. Identical hormone treatments were applied to “wild-type” (non-mutated) and single point VDR mutations. 1,25D displayed a significant drop in activity caused by these mutations, while the ability of resveratrol to activate VDR was only modestly attenuated. One possible interpretation of these results is that resveratrol may affect VDR activity indirectly, perhaps via the ability of resveratrol to activate SIRT1, an enzyme which has been shown to deacetylate (and thereby activate) other nuclear receptors such as the liver X receptor (LXR). In support of this hypothesis, radiolabeled 1,25D displacement assays revealed an increase in bound radiolabeled 1,25D only in the presence of resveratrol, suggesting that direct binding of resveratrol to VDR is unlikely. Additionally, we observed increased transcriptional activity in response to resveratrol in a subset of other nuclear receptors, including the liver X receptor (LXR), which is closely related to VDR and is known to be deacetylated by SIRT1. Finally, we tested receptor-mediated transcriptional activity in a system containing VDR in the absence and presence of overexpressed SIRT1. Transcriptional activity was higher in cells expressing SIRT1, and synergistic activity of 1,25D combined with resveratrol was observed. We are currently conducting additional experiments employing the VDR/SIRT1 assay in multiple cellular contexts. In conclusion, this study elucidates, for the first time, a potential novel pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol

The 2011 Eruption of the Recurrent Nova T Pyxidis; the Discovery, the Pre-eruption Rise, the Pre-eruption Orbital Period, and the Reason for the Long Delay

We report the discovery by M. Linnolt on JD 2455665.7931 (UT 2011 April 14.29) of the sixth eruption of the recurrent nova T Pyxidis. This discovery was made just as the initial fast rise was starting, so with fast notification and response by observers worldwide, the entire initial rise was covered (the first for any nova), and with high time resolution in three filters. The speed of the rise peaked at 9 mag/day, while the light curve is well fit over only the first two days by a model with a uniformly expanding sphere. We also report the discovery by R. Stubbings of a pre-eruption rise starting 18 days before the eruption, peaking 1.1 mag brighter than its long-time average, and then fading back towards quiescence 4 days before the eruption. This unique and mysterious behavior is only the fourth known anticipatory rise closely spaced before a nova eruption. We present 19 timings of photometric minima from 1986 to February 2011, where the orbital period is fast increasing with P/dot{P}=313,000 yrs. From 2008-2011, T Pyx had a small change in this rate of increase, so that the orbital period at the time of eruption was 0.07622950+-0.00000008 days. This strong and steady increase of the orbital period can only come from mass transfer, for which we calculate a rate of 1.7-3.5x10^-7 Mo/yr. We report 6116 magnitudes between 1890 and 2011, for an average B=15.59+-0.01 from 1967-2011, which allows for an eruption in 2011 if the blue flux is nearly proportional to the accretion rate. The ultraviolet-optical-infrared spectral energy distribution is well fit by a power law with flux proportional to nu^1.0, although the narrow ultraviolet region has a tilt with a fit of \nu^{1/3}. We prove that most of the T Pyx light is not coming from a disk, or any superposition of blackbodies, but rather is coming from some nonthermal source.Comment: ApJ submitted, 62 pages, 8 figures; much added data, updated analysi

La asociación : revista de primera enseñanza: Año XI Número 541 - (07/07/23)

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end-stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next-generation sequencing have enabled rapid and cost-effective sequencing of large amounts of DNA. Next-generation sequencing-based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early-onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at-risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health-care systems

Cost-effectiveness of targeted exome analysis as a diagnostic test in glomerular diseases

Background: Despite the emergence of diagnostic and clinical utility evidence in nephrology, publicly funded access to genomic testing is restricted in most health care systems. To establish genomic sequencing as a clinical test, an evaluation of cost-effectiveness is urgently required. Methods: An economic evaluation, informed by a primary clinical study and available clinical evidence and guidelines in nephrology, was performed to evaluate the cost-effectiveness and optimal timing of exome sequencing (ES) in adults and children with suspected monogenic glomerular diseases compared with nongenomic investigations (NGIs). Six diagnostic strategies reflecting current practice and recommended models of care in Australia were modeled: (i) NGIs, (ii) late gene panel followed by ES, (iii) late ES, (iv) early gene panel, (v) early gene panel followed by ES, and (vi) early ES. Results: ES with targeted analysis achieved a diagnosis in 23 of 63 (36.5%) adults and 10 of 24 (41.6%) children. NGIs were estimated to diagnose 4.0% of children, with an average estimated cost of AU$6120 per child. Integrating ES as a first-line test in children was cost saving, with an incremental cost saving of AU$3230 per additional diagnosis compared with NGIs. In adults, NGIs was estimated to diagnose 8% of patients, with an average estimated cost of AU$1830 per person. In adults, integrating ES early resulted in an incremental cost per additional diagnosis of AU$5460 relative to NGIs. Conclusions: Early ES with targeted analysis was effective for diagnosing monogenic kidney disease, with substantial cost savings in children

Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm

Background: Proteinuria is a common clinical presentation, the diagnostic workup for which involves many noninvasive and invasive investigations. We report on two siblings that highlight the clinically relevant functional role of cubulin for albumin resorption in the proximal tubule and supports the use of genomic sequencing early in the diagnostic work up of patients who present with proteinuria. Case presentation: An 8-year-old boy was referred with an incidental finding of proteinuria. All preliminary investigations were unremarkable. Further assessment revealed consanguineous family history and a brother with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global glomerular basement membrane thinning on electron microscopy. Chromosomal microarray revealed long continuous stretches of homozygosity (LCSH) representing ~ 4.5% of the genome. Shared regions of LCSH between the brothers were identified and their further research genomic analysis implicated a homozygous stop-gain variant in CUBN (10p12.31). Conclusions: CUBN mutations have been implicated as a hereditary cause of megaloblastic anaemia and variable proteinuria. This is the second reported family with isolated proteinuria due to biallelic CUBN variants in the absence of megaloblastic anaemia, demonstrating the ability of genomic testing to identify genetic causes of nephropathy within expanding associated phenotypic spectra. Genomic sequencing, undertaken earlier in the diagnostic trajectory, may reduce the need for invasive investigations and the time to definitive diagnosis for patients and families

The Galactic Inner Halo: Searching for White Dwarfs and Measuring the Fundamental Galactic Constant, Vo/Ro

We establish an extragalactic, zero-motion frame of reference within the deepest optical image of a globular star cluster, an HST 123-orbit exposure of M4 (GO 8679, cycle 9). The line of sight beyond M4 (l,b (deg) = 351,16) intersects the inner halo (spheroid) of our Galaxy at a tangent-point distance of 7.6 kpc (for Ro = 8 kpc). We isolate these spheroid stars from the cluster based on their proper motions over the 6-year baseline between these and previous epoch HST data (GO 5461, cycle 4). Distant background galaxies are also found on the same sight line using image-morphology techniques. This fixed reference frame allows us to independently determine the fundamental Galactic constant, Vo/Ro = 25.3 +/- 2.6 km/s/kpc, thus providing a velocity of the Local Standard of Rest, v = 202.7 +/- 24.7 km/s for Ro = 8.0 +/- 0.5 kpc. Secondly, the galaxies allow a direct measurement of M4's absolute proper motion, mu_total = 22.57 +/- 0.76 mas/yr, in excellent agreement with recent studies. The clear separation of galaxies from stars in these deep data also allow us to search for inner-halo white dwarfs. We model the conventional Galactic contributions of white dwarfs along our line of sight and predict 7.9 (thin disk), 6.3 (thick disk) and 2.2 (spheroid) objects to the limiting magnitude at which we can clearly delineate stars from galaxies (V = 29). An additional 2.5 objects are expected from a 20% white dwarf dark halo consisting of 0.5 Mo objects, 70% of which are of the DA type. After considering the kinematics and morphology of the objects in our data set, we find the number of white dwarfs to be consistent with the predictions for each of the conventional populations. However, we do not find any evidence for dark halo white dwarfs.Comment: 31 pages, including 6 diagrams and 2 tables. Accepted for publication in Ap