Toll-like receptors and NOD-like receptors in rheumatic diseases

The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease - the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4 are being implicated in the pathology of rheumatoid arthritis, ankylosing spondylitis, lyme arthritis and osteoarthritis. Nalp3 has been identified as a key NLR for IL-1β production and has been shown to have a particular role in gout. These findings present new therapeutic opportunities, possibly allowing for the replacement of biologics with small molecule inhibitors

Which children and young people are excluded from school? Findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) - poster abstract

Poster abstract presented at Spring Meeting for Clinician Scientists in Training 2015BACKGROUND: School exclusion is a disciplinary method used to remove a child from the school environment. It is known to affect certain groups disproportionately, including boys, some ethnic minorities, children in care, children in poverty, and children with special educational needs. Population-based studies on wider characteristics of excluded pupils are scarce. The aim of this study was to describe factors associated with school exclusion in the Avon Longitudinal Study of Parents and Children (ALSPAC), focussing on neurodevelopment and mental health. METHODS: ALSPAC is a prospective population-based British birth cohort study, with the initial sample consisting of 14 541 pregnancies. The study has data for whether a child has been permanently excluded from school up to the age of 8 years as reported by parents and also permanent and fixed period exclusions in the preceding 12 months as reported by parents and young people at age 16 years. Upstream risk factors were assessed for associations with exclusion on univariable analysis. The association with social communication difficulties was investigated with multivariable logistic regression. FINDINGS: Data for exclusions up to the age of 8 years were available for 8245 ALSPAC participants and 4482 participants for exclusion at age 16 years. 53 pupils (0·6%) were excluded from school by age 8 years, and 390 (8·7%) at age 16 years. The odds of exclusion by 8 years and at 16 years were increased with male sex (p=0·001 and p<0·0001, respectively), low family income (p=0·014 and p<0·0001), family adversity (p<0·0001 for both), maternal psychopathology (p=0·013 and p=0·004), low intelligence quotient (p=0·041 and p<0·0001), mental health difficulties (p<0·0001 for both), psychiatric disorder (p<0·0001 for both), social communication difficulties (p<0·0001 for both), antisocial activities (p=0·004 and p<0·0001), bullying or being bullied (p=0·005 and p<0·0001), low educational attainment (p<0·0001 for both), and increased special educational needs (p<0·0001 for both). On multivariable analysis, having social communication difficulties above a clinical threshold on the Social Communication Disorders Checklist was strongly associated with exclusion by 8 years (odds ratio 7·4, 95% CI 3·6-15·4) and at 16 years (2·3, 1·5-3·5), after adjustment for relevant confounders. INTERPRETATION: Although cohort attrition and small numbers of exclusions at 8 years are limitations, this study suggests that school exclusion is associated with numerous risk factors identifiable at or before primary school entry. Child health professionals have an important role in the holistic assessment of children who are excluded, or who are at risk of school exclusion. There is particular need to ensure that mental health and neurodevelopmental difficulties are appropriately recognised and supported. FUNDING: National Institute for Health Research Academic Clinical Fellowship

Awaking the vacuum in relativistic stars

Void of any inherent structure in classical physics, the vacuum has revealed to be incredibly crowded with all sorts of processes in relativistic quantum physics. Yet, its direct effects are usually so subtle that its structure remains almost as evasive as in classical physics. Here, in contrast, we report on the discovery of a novel effect according to which the vacuum is compelled to play an unexpected central role in an astrophysical context. We show that the formation of relativistic stars may lead the vacuum energy density of a quantum field to an exponential growth. The vacuum-driven evolution which would then follow may lead to unexpected implications for astrophysics, while the observation of stable neutron-star configurations may teach us much on the field content of our Universe.Comment: To appear in Phys. Rev. Let

Semiclassical charged black holes with a quantized massive scalar field

Semiclassical perturbations to the Reissner-Nordstrom metric caused by the presence of a quantized massive scalar field with arbitrary curvature coupling are found to first order in \epsilon = \hbar/M^2. The DeWitt-Schwinger approximation is used to determine the vacuum stress-energy tensor of the massive scalar field. When the semiclassical perturbation are taken into account, we find extreme black holes will have a charge-to-mass ratio that exceeds unity, as measured at infinity. The effects of the perturbations on the black hole temperature (surface gravity) are studied in detail, with particular emphasis on near extreme ``bare'' states that might become precisely zero temperature ``dressed'' semiclassical black hole states. We find that for minimally or conformally coupled scalar fields there are no zero temperature solutions among the perturbed black holes.Comment: 19 pages; 1 figure; ReVTe

Abundances of Molecular Species in Barnard 68

Abundances for 5 molecules (C18O, CS, NH3, H2CO, and C3H2) and 1 molecular ion (N2H+) and upper limits for the abundances of 1 molecule (13CO) and 1 molecular ion (HCO+) are derived for gas within the Bok globule Barnard 68 (B68). The abundances were determined using our own BIMA millimeter interferometer data and single-dish data gathered from the literature, in conjunction with a Monte Carlo radiative transfer model. Since B68 is the only starless core to have its density structure strongly constrained via extinction mapping, a major uncertainty has been removed from these determinations. All abundances for B68 are lower than those derived for translucent and cold dense clouds, but perhaps only significantly for N2H+, NH3, and C3H2. Depletion of CS toward the extinction peak of B68 is hinted at by the large offset between the extinction peak and the position of maximum CS line brightness. Abundances derived here for C18O and N2H+ are consistent with other, recently determined values at positions observed in common.Comment: 16 pages, 1 figure, accepted by AJ, typo corrected, reference removed in Section 4.

Conspecific chemical cues facilitate mate trailing by invasive Argentine black and white tegus

Squamate reptiles (snakes and lizards) rely on chemical cues from conspecifics to search the environment for potential mates. How such cues are used by invasive species to facilitate reproduction, especially seasonally, is a key question that can inform management practices. The Argentine black and white tegu (Salvator merianae) is an invasive reptile species in south Florida threatening native fauna in biodiverse regions such as Everglades National Park. While some information exists on the reproductive ecology of this species in its native range in South America, the chemical ecology of S. merianae is unclear especially in its invasive range. By testing both male (n = 7) and female (n = 7) tegus in a Y-maze apparatus, we assessed if either sex follows chemical trails left by conspecifics and if behaviors were sex- or season-specific. We conducted three types of trials where conspecifics created odor trails: Male-only (male scent only in base and one arm of Y), Female-only, and Male vs. female. Males did not preferentially follow scent trails from either sex, but they did differentially investigate conspecific scent from both sexes. Seasonally, males showed increased rates of chemosensory sampling (rates of tongue-flicking) during the spring (breeding season; March-May) compared to fall (non-breeding season; September-November). Males also had reduced turning and pausing behavior while trailing in the spring. Female tegus exhibited stronger conspecific trailing abilities than males, following both male and female scent trails, and they explored the maze less before making an arm choice. Females also investigated the scent trails intensely compared to males (more passes in scented arms, more time with scent trails). Our results demonstrate for the first time that females of an invasive reptile species can follow conspecific scent trails. Given the strong female responses to odor, sex-specific targeting of tegus via application of a conspecific chemical cue in traps could enhance removal rates of females during the breeding season

Do different depression phenotypes have different risks for recurrent coronary heart disease?

Although research has consistently established that depression and elevated depressive symptoms are associated with an increased risk of coronary heart disease (CHD) recurrence and mortality, clinical trials have failed to show that conventional depression interventions offset this risk. As depression is a complex and heterogeneous syndrome, we believe that examining simpler, or intermediary, phenotypes rather than one complex phenotype may allow better identification of those at particular risk of CHD recurrence and mortality. This approach may further contribute to the development of specific depression treatments that would improve medical outcomes. Although there are many possible intermediary phenotypes (IPs), specifiers and dimensions of depression, we will focus on only two when considering the relation between depression and risk of CHD recurrence and mortality: Incident Depression and Anhedonic Depression. Future research on IPs of depression is needed to clarify which are associated with the greatest risk for CHD recurrence and mortality and which, if any, are benign. Theoretical advances in depression phenotyping may also help elucidate the behavioural and biological mechanisms underlying the increased risk of CHD among patients with specific depression phenotypes. Finally, tests of depression interventions may be guided by this new theoretical approach

Chemotherapy and Stem Cell Transplantation Increase p16

AbstractThe expression of markers of cellular senescence increases exponentially in multiple tissues with aging. Age-related physiological changes may contribute to adverse outcomes in cancer survivors. To investigate the impact of high dose chemotherapy and stem cell transplantation on senescence markers in vivo, we collected blood and clinical data from a cohort of 63 patients undergoing hematopoietic cell transplantation. The expression of p16INK4a, a well-established senescence marker, was determined in T-cells before and 6months after transplant. RNA sequencing was performed on paired samples from 8 patients pre- and post-cancer therapy. In patients undergoing allogeneic transplant, higher pre-transplant p16INK4a expression was associated with a greater number of prior cycles of chemotherapy received (p=0.003), prior autologous transplantation (p=0.01) and prior exposure to alkylating agents (p=0.01). Transplantation was associated with a marked increase in p16INK4a expression 6months following transplantation. Patients receiving autologous transplant experienced a larger increase in p16INK4a expression (3.1-fold increase, p=0.002) than allogeneic transplant recipients (1.9-fold increase, p=0.0004). RNA sequencing of T-cells pre- and post- autologous transplant or cytotoxic chemotherapy demonstrated increased expression of transcripts associated with cellular senescence and physiological aging. Cytotoxic chemotherapy, especially alkylating agents, and stem cell transplantation strongly accelerate expression of a biomarker of molecular aging in T-cells