Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio

The Relationship Between Stigma and Health-Related Quality of Life in People Living with HIV Who Have Full Access to Antiretroviral Treatment: An Assessment of Earnshaw and Chaudoir's HIV Stigma Framework Using Empirical Data.

The aim was to empirically test the tenets of Earnshaw and Chaudoir's HIV stigma framework and its potential covariates for persons living with HIV in Sweden. Partial least squares structural equation modelling was used on survey data from 173 persons living with HIV in Sweden. Experiencing stigma was reported to a higher extent by younger persons and by women who had migrated to Sweden. As expected, anticipated stigma was related to lower Physical functioning, and internalized stigma to lower Emotional wellbeing. In contrast to that hypothesized by the HIV stigma framework, enacted stigma was not related to Physical functioning and no relationships were found between HIV-related stigma and antiretroviral adherence. These results indicate that the HIV stigma framework may need to be revised for contexts where a very high proportion of persons living with HIV are diagnosed and under efficient treatment

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition

Hedgehog signaling drives oncogenesis in several cancers and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened. However, resistance to Smoothened inhibitors occurs via genetic changes of Smoothened or other downstream Hedgehog components. Here, we overcome these resistance mechanisms by modulating GLI transcription via inhibition of BET bromodomain proteins. We show the BET bromodomain protein, BRD4, regulates GLI transcription downstream of SMO and SUFU and chromatin immunoprecipitation studies reveal BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in engagement of these sites upon treatment with JQ1, a small molecule inhibitor targeting BRD4. Globally, genes associated with medulloblastoma-specific GLI1 binding sites are downregulated in response to JQ1 treatment, supporting direct regulation of GLI activity by BRD4. Notably, patient- and GEMM-derived Hedgehog-driven tumors (basal cell carcinoma, medulloblastoma and atypical teratoid/rhabdoid tumor) respond to JQ1 even when harboring genetic lesions rendering them resistant to Smoothened antagonists

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

Disentangling the stigma of HIV/AIDS from the stigmas of drugs use, commercial sex and commercial blood donation – a factorial survey of medical students in China

BackgroundHIV/AIDS related stigma interferes with the provision of appropriate care and support for people living with HIV/AIDS. Currently, programs to address the stigma approach it as if it occurs in isolation, separate from the co-stigmas related to the various modes of disease transmission including injection drug use (IDU) and commercial sex (CS). In order to develop better programs to address HIV/AIDS related stigma, the inter-relationship (or \u27layering\u27) between HIV/AIDS stigma and the co-stigmas needs to be better understood. This paper describes an experimental study for disentangling the layering of HIV/AIDS related stigmas.MethodsThe study used a factorial survey design. 352 medical students from Guangzhou were presented with four random vignettes each describing a hypothetical male. The vignettes were identical except for the presence of a disease diagnosis (AIDS, leukaemia, or no disease) and a co-characteristic (IDU, CS, commercial blood donation (CBD), blood transfusion or no co-characteristic). After reading each vignette, participants completed a measure of social distance that assessed the level of stigmatising attitudes.ResultsBivariate and multivariable analyses revealed statistically significant levels of stigma associated with AIDS, IDU, CS and CBD. The layering of stigma was explored using a recently developed technique. Strong interactions between the stigmas of AIDS and the co-characteristics were also found. AIDS was significantly less stigmatising than IDU or CS. Critically, the stigma of AIDS in combination with either the stigmas of IDU or CS was significantly less than the stigma of IDU alone or CS alone.ConclusionThe findings pose several surprising challenges to conventional beliefs about HIV/AIDS related stigma and stigma interventions that have focused exclusively on the disease stigma. Contrary to the belief that having a co-stigma would add to the intensity of stigma attached to people with HIV/AIDS, the findings indicate the presence of an illness might have a moderating effect on the stigma of certain co-characteristics like IDU. The strong interdependence between the stigmas of HIV/AIDS and the co-stigmas of IDU and CS suggest that reducing the co-stigmas should be an integral part of HIV/AIDS stigma intervention within this context.<br /

Routine MRI findings of the asymptomatic foot in diabetic patients with unilateral Charcot foot

<p>Abstract</p> <p>Background</p> <p>Imaging studies of bones in patients with sensory deficits are scarce.</p> <p>Aim</p> <p>To investigate bone MR images of the lower limb in diabetic patients with severe sensory polyneuropathy, and in control subjects without sensory deficits.</p> <p>Methods</p> <p>Routine T1 weighted and T2-fat-suppressed-STIR-sequences without contrast media were performed of the asymptomatic foot in 10 diabetic patients with polyneuropathy and unilateral inactive Charcot foot, and in 10 matched and 10 younger, non-obese unmatched control subjects. Simultaneously, a Gadolinium containing phantom was also assessed for reference. T1 weighted signal intensity (SI) was recorded at representative regions of interest at the peritendineal soft tissue, the tibia, the calcaneus, and at the phantom. Any abnormal skeletal morphology was also recorded.</p> <p>Results</p> <p>Mean SI at the soft tissue, the calcaneus, and the tibia, respectively, was 105%, 105% and 84% of that at the phantom in the matched and unmatched control subjects, compared to 102% (soft tissue), 112% (calcaneus) and 64% (tibia) in the patients; differences of tibia vs. calcaneus or soft tissue were highly significant (p < 0.005). SI at the tibia was lower in the patients than in control subjects (p < 0.05). Occult traumatic skeletal lesions were found in 8 of the 10 asymptomatic diabetic feet (none in the control feet).</p> <p>Conclusion</p> <p>MR imaging did not reveal grossly abnormal bone marrow signalling in the limbs with severe sensory polyneuropathy, but occult sequelae of previous traumatic injuries.</p

Exploring the nature of stigmatising beliefs about depression and help-seeking: Implications for reducing stigma

<p>Abstract</p> <p>Background</p> <p>In-depth and structured evaluation of the stigma associated with depression has been lacking. This study aimed to inform the design of interventions to reduce stigma by systematically investigating community perceptions of beliefs about depression according to theorised dimensional components of stigma.</p> <p>Methods</p> <p>Focus group discussions were held with a total of 23 adults with personal experience of depression. The discussions were taped, transcribed and thematically analysed.</p> <p>Results</p> <p>Participants typically reported experiencing considerable stigma, particularly that others believe depressed people are responsible for their own condition, are undesirable to be around, and may be a threat. Participants expressed particular concerns about help-seeking in the workplace and from mental health professionals.</p> <p>Conclusion</p> <p>Findings indicate that interventions to reduce the stigma of depression should target attributions of blame; reduce avoidance of depressed people; label depression as a 'health condition' rather than 'mental illness'; and improve responses of help-sources (i.e. via informing professionals of client fears).</p

Lymphoid Tissue Damage in HIV-1 Infection Depletes Naïve T Cells and Limits T Cell Reconstitution after Antiretroviral Therapy

Highly active antiretroviral therapy (HAART) can suppress HIV-1 replication and normalize the chronic immune activation associated with infection, but restoration of naïve CD4+ T cell populations is slow and usually incomplete for reasons that have yet to be determined. We tested the hypothesis that damage to the lymphoid tissue (LT) fibroblastic reticular cell (FRC) network contributes to naïve T cell loss in HIV-1 infection by restricting access to critical factors required for T cell survival. We show that collagen deposition and progressive loss of the FRC network in LTs prior to treatment restrict both access to and a major source of the survival factor interleukin-7 (IL-7). As a consequence, apoptosis within naïve T cell populations increases significantly, resulting in progressive depletion of both naïve CD4+ and CD8+ T cell populations. We further show that the extent of loss of the FRC network and collagen deposition predict the extent of restoration of the naïve T cell population after 6 month of HAART, and that restoration of FRC networks correlates with the stage of disease at which the therapy is initiated. Because restoration of the FRC network and reconstitution of naïve T cell populations are only optimal when therapy is initiated in the early/acute stage of infection, our findings strongly suggest that HAART should be initiated as soon as possible. Moreover, our findings also point to the potential use of adjunctive anti-fibrotic therapies to avert or moderate the pathological consequences of LT fibrosis, thereby improving immune reconstitution