A predicted astrometric microlensing event by a nearby white dwarf

We used the Tycho-Gaia Astrometric Solution catalogue, part of the Gaia Data Release 1, to search for candidate astrometric microlensing events expected to occur within the remaining lifetime of the Gaia satellite. Our search yielded one promising candidate. We predict that the nearby DQ type white dwarf LAWD 37 (WD 1142-645) will lens a background star and will reach closest approach on November 11th 2019 ($\pm$ 4 days) with impact parameter $380\pm10$ mas. This will produce an apparent maximum deviation of the source position of $2.8\pm0.1$ mas. In the most propitious circumstance, Gaia will be able to determine the mass of LAWD 37 to $\sim3\%$. This mass determination will provide an independent check on atmospheric models of white dwarfs with helium rich atmospheres, as well as tests of white dwarf mass radius relationships and evolutionary theory

Chiropractic and self-care for back-related leg pain: design of a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Back-related leg pain (BRLP) is a common variation of low back pain (LBP), with lifetime prevalence estimates as high as 40%. Often disabling, BRLP accounts for greater work loss, recurrences, and higher costs than uncomplicated LBP and more often leads to surgery with a lifetime incidence of 10% for those with severe BRLP, compared to 1-2% for those with LBP.</p> <p>In the US, half of those with back-related conditions seek CAM treatments, the most common of which is chiropractic care. While there is preliminary evidence suggesting chiropractic spinal manipulative therapy is beneficial for patients with BRLP, there is insufficient evidence currently available to assess the effectiveness of this care.</p> <p>Methods/Design</p> <p>This study is a two-site, prospective, parallel group, observer-blinded randomized clinical trial (RCT). A total of 192 study patients will be recruited from the Twin Cities, MN (n = 122) and Quad Cities area in Iowa and Illinois (n = 70) to the research clinics at WHCCS and PCCR, respectively.</p> <p>It compares two interventions: chiropractic spinal manipulative therapy (SMT) plus home exercise program (HEP) to HEP alone (minimal intervention comparison) for patients with subacute or chronic back-related leg pain.</p> <p>Discussion</p> <p>Back-related leg pain (BRLP) is a costly and often disabling variation of the ubiquitous back pain conditions. As health care costs continue to climb, the search for effective treatments with few side-effects is critical. While SMT is the most commonly sought CAM treatment for LBP sufferers, there is only a small, albeit promising, body of research to support its use for patients with BRLP.</p> <p>This study seeks to fill a critical gap in the LBP literature by performing the first full scale RCT assessing chiropractic SMT for patients with sub-acute or chronic BRLP using important <b>patient-oriented </b>and <b>objective biomechanical </b>outcome measures.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00494065">NCT00494065</a></p

Viral Replication Rate Regulates Clinical Outcome and CD8 T Cell Responses during Highly Pathogenic H5N1 Influenza Virus Infection in Mice

Since the first recorded infection of humans with H5N1 viruses of avian origin in 1997, sporadic human infections continue to occur with a staggering mortality rate of >60%. Although sustained human-to-human transmission has not occurred yet, there is a growing concern that these H5N1 viruses might acquire this trait and raise the specter of a pandemic. Despite progress in deciphering viral determinants of pathogenicity, we still lack crucial information on virus/immune system interactions pertaining to severe disease and high mortality associated with human H5N1 influenza virus infections. Using two human isolates of H5N1 viruses that differ in their pathogenicity in mice, we have defined mechanistic links among the rate of viral replication, mortality, CD8 T cell responses, and immunopathology. The extreme pathogenicity of H5N1 viruses was directly linked to the ability of the virus to replicate rapidly, and swiftly attain high steady-state titers in the lungs within 48 hours after infection. The remarkably high replication rate of the highly pathogenic H5N1 virus did not prevent the induction of IFN-β or activation of CD8 T cells, but the CD8 T cell response was ineffective in controlling viral replication in the lungs and CD8 T cell deficiency did not affect viral titers or mortality. Additionally, BIM deficiency ameliorated lung pathology and inhibited T cell apoptosis without affecting survival of mice. Therefore, rapidly replicating, highly lethal H5N1 viruses could simply outpace and overwhelm the adaptive immune responses, and kill the host by direct cytopathic effects. However, therapeutic suppression of early viral replication and the associated enhancement of CD8 T cell responses improved the survival of mice following a lethal H5N1 infection. These findings suggest that suppression of early H5N1 virus replication is key to the programming of an effective host response, which has implications in treatment of this infection in humans

MRE11 as a predictive biomarker of outcome following radiotherapy in bladder cancer

Purpose Organ-confined muscle-invasive bladder cancer (MIBC) is treated with cystectomy or bladder preservation techniques, including radiotherapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome following radiotherapy but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from two major clinical trials. Methods and Materials Samples from the BCON and BC2001 randomised controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in three UK centres. Results Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor inter-centre scoring agreement (Kappa 0.32, 95% CI 0.17-0.47). There were no significant associations between MRE11 scores and cause-specific survival (CSS) identified in BCON (n=132) and BC2001 (n=221) samples. Re-optimised staining improved agreement between scores from BCON tissue microarrays (n=116), but MRE11 expression was not prognostic for CSS. Conclusions Manual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods and/or a reassessment of how DNA-damage response relates to clinical outcomes

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

The epidemiology and treatment of gout

Neil W McGillInstitute of Rheumatology and Orthopaedics, Royal Prince Alfred Hospital, Camperdown, Sydney, AustraliaAbstract: The development and expression of gout depends on three key steps: (1) chronic hyperuricemia, (2) the growth of monosodium urate (MSU) crystals, and (3) interaction between MSU crystals and the inflammatory system. Epidemiological studies have continued to improve our understanding of the environmental and genetic factors which influence chronic hyperuricemia and gout. The influence of obesity, alcohol, race, sex, age, and specific dietary components will be discussed below. The primary mechanism of hyperuricemia is insufficient renal clearance of uric acid which in turn is dependent on transport of uric acid in the proximal renal tubule. Knowledge of the transport mechanisms has improved understanding of the genetic influences on gout and is relevant to understanding of the effects of drugs which can increase or decrease renal uric acid clearance. The application of established principles of management including diagnosis through crystal identification, the gradual introduction of hypouricemic therapy with the use of prophylaxis to reduce the risk of flares, identification of a suitably low target of plasma urate, a progressive increase in therapy to achieve the target and taking steps to encourage good compliance, has the potential to improve outcomes for patients with this very common affliction. The potential role for new therapies will also be discussed.Keywords: gout, hyperuricemia, allopurinol, febuxostat, lesinurad, pegloticas