We report on Bayesian parameter estimation of the mass and equatorial radius of the millisecond pulsar PSR J0030+0451, conditional on pulse-profile modeling of Neutron Star Interior Composition ...Explorer X-ray spectral-timing event data. We perform relativistic ray-tracing of thermal emission from hot regions of the pulsar's surface. We assume two distinct hot regions based on two clear pulsed components in the phase-folded pulse-profile data; we explore a number of forms (morphologies and topologies) for each hot region, inferring their parameters in addition to the stellar mass and radius. For the family of models considered, the evidence (prior predictive probability of the data) strongly favors a model that permits both hot regions to be located in the same rotational hemisphere. Models wherein both hot regions are assumed to be simply connected circular single-temperature spots, in particular those where the spots are assumed to be reflection-symmetric with respect to the stellar origin, are strongly disfavored. For the inferred configuration, one hot region subtends an angular extent of only a few degrees (in spherical coordinates with origin at the stellar center) and we are insensitive to other structural details; the second hot region is far more azimuthally extended in the form of a narrow arc, thus requiring a larger number of parameters to describe. The inferred mass M and equatorial radius Req are, respectively, 1.34 − 0.16 + 0.15 M and 12.71 − 1.19 + 1.14 km , while the compactness GM R eq c 2 = 0.156 − 0.010 + 0.008 is more tightly constrained; the credible interval bounds reported here are approximately the 16% and 84% quantiles in marginal posterior mass.
Abstract
In recent years our understanding of the dense matter equation of state (EOS) of neutron stars has significantly improved by analyzing multimessenger data from radio/X-ray pulsars, ...gravitational wave events, and from nuclear physics constraints. Here we study the additional impact on the EOS from the jointly estimated mass and radius of PSR J0740+6620, presented in Riley et al. by analyzing a combined data set from X-ray telescopes NICER and XMM-Newton. We employ two different high-density EOS parameterizations: a piecewise-polytropic (PP) model and a model based on the speed of sound in a neutron star (CS). At nuclear densities these are connected to microscopic calculations of neutron matter based on chiral effective field theory (EFT) interactions. In addition to the new NICER data for this heavy neutron star, we separately study constraints from the radio timing mass measurement of PSR J0740+6620, the gravitational wave events of binary neutron stars GW190425 and GW170817, and for the latter the associated kilonova AT2017gfo. By combining all these, and the NICER mass–radius estimate of PSR J0030+0451, we find the radius of a 1.4
M
⊙
neutron star to be constrained to the 95% credible ranges
12.33
−
0.81
+
0.76
km
(PP model) and
12.18
−
0.79
+
0.56
km
(CS model). In addition, we explore different chiral EFT calculations and show that the new NICER results provide tight constraints for the pressure of neutron star matter at around twice saturation density, which shows the power of these observations to constrain dense matter interactions at intermediate densities.
Both the mass and radius of the millisecond pulsar PSR J0030+0451 have been inferred via pulse-profile modeling of X-ray data obtained by NASA's Neutron Star Interior Composition Explorer (NICER) ...mission. In this Letter we study the implications of the mass-radius inference reported for this source by Riley et al. for the dense matter equation of state (EoS), in the context of prior information from nuclear physics at low densities. Using a Bayesian framework we infer central densities and EoS properties for two choices of high-density extensions: a piecewise-polytropic model and a model based on assumptions of the speed of sound in dense matter. Around nuclear saturation density these extensions are matched to an EoS uncertainty band obtained from calculations based on chiral effective field theory interactions, which provide a realistic description of atomic nuclei as well as empirical nuclear matter properties within uncertainties. We further constrain EoS expectations with input from the current highest measured pulsar mass; together, these constraints offer a narrow Bayesian prior informed by theory as well as laboratory and astrophysical measurements. The NICER mass-radius likelihood function derived by Riley et al. using pulse-profile modeling is consistent with the highest-density region of this prior. The present relatively large uncertainties on mass and radius for PSR J0030+0451 offer, however, only a weak posterior information gain over the prior. We explore the sensitivity to the inferred geometry of the heated regions that give rise to the pulsed emission, and find a small increase in posterior gain for an alternative (but less preferred) model. Lastly, we investigate the hypothetical scenario of increasing the NICER exposure time for PSR J0030+0451.
Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen‐reactive Tregs (arTregs) are ...more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short‐term cultures using good manufacturing practice‐compliant reagents. This process uses CD40L‐activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100‐ to 1600‐fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen‐expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model.
This study details a good manufacturing practice‐compliant process for short‐term selective expansion of donoralloantigen‐reactive regulatory T cells for therapeutic applications in transplantation.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent modeling of Neutron Star Interior Composition Explorer observations of thermal X-ray pulsations from the surface of the isolated millisecond pulsar PSR J0030+0451 suggests that the hot ...emitting regions on the pulsar's surface are far from antipodal, which is at odds with the classical assumption that the magnetic field in the pulsar magnetosphere is predominantly that of a centered dipole. Here, we review these results and examine previous attempts to constrain the magnetospheric configuration of PSR J0030+0451. To the best of our knowledge, there is in fact no direct observational evidence that PSR J0030+0451's magnetic field is a centered dipole. Developing models of physically motivated, non-canonical magnetic field configurations and the currents that they can support poses a challenging task. However, such models may have profound implications for many aspects of pulsar research, including pulsar braking, estimates of birth velocities, and interpretations of multi-wavelength magnetospheric emission.
The Neutron Star Interior Composition Explorer collaboration recently published a joint estimate of the mass and the radius of PSR J0030+0451, derived via X-ray pulse-profile modeling. Raaijmakers et ...al. explored the implications of this measurement for the dense matter equation of state (EOS) using two parameterizations of the high-density EOS: a piecewise-polytropic model, and a model based on the speed of sound in neutron stars (NSs). In this work we obtain further constraints on the EOS following this approach, but we also include information about the tidal deformability of NSs from the gravitational wave signal of the compact binary merger GW170817. We compare the constraints on the EOS to those set by the recent measurement of a 2.14 M pulsar, included as a likelihood function approximated by a Gaussian, and find a small increase in information gain. To show the flexibility of our method, we also explore the possibility that GW170817 was a NS-black hole merger, which yields weaker constraints on the EOS.
Background
The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality ...from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.
Methods
A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
Results
Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P
interaction = .81), pretrial PSA testing (P
interaction = .52), and comorbidity (P
interaction = .68).
Conclusions
After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.
The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC) highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for association to schizophrenia. After ...follow-up in independent samples, seven loci attained genome-wide significance (GWS), but multi-locus tests suggested some SNPs that did not do so represented true associations. We tested 78 of the 81 SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar disorder, and 2878 controls. In CLOZUK, we obtained significant replication to the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs for which we had data that were reported as GWS by the PGC. After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support. In bipolar disorder, we also obtained significant evidence for association for 21% of the alleles that had been associated with schizophrenia in the PGC. Our study independently confirms association to three loci previously reported to be GWS in schizophrenia, and identifies the first GWS evidence in schizophrenia for a further three loci. Given the number of independent replications and the power of our sample, we estimate 98% (confidence interval (CI) 78-100%) of the original set of 78 SNPs represent true associations. We also provide strong evidence for overlap in genetic risk between schizophrenia and bipolar disorder.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary Objective Pain in knee osteoarthritis (OA) has historically been attributed to peripheral pathophysiology; however, the poor correspondence between objective measures of disease severity and ...clinical symptoms suggests that non-local factors, such as altered central processing of painful stimuli, also contribute to clinical pain in knee OA. Consistent with this notion, recent evidence demonstrates that patients with knee OA exhibit increased sensitivity to painful stimuli at body sites unaffected by clinical pain. Design In order to further investigate the contribution of altered pain processing to knee OA pain, the current study tested the hypothesis that symptomatic knee OA is associated with enhanced sensitivity to experimental pain stimuli at the knee and at remote body sites unaffected by clinical pain. We further anticipated that pain sensitivity would differ as a function of the OA symptom severity. Older adults with and without symptomatic knee OA completed a series of experimental pain assessments. A median split of the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) was used to stratify participants into low vs high OA symptom severity. Results Compared to controls and the low symptom group, individuals in the high symptom group were more sensitive to suprathreshold heat stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in the low symptomatic OA group subgroup exhibited experimental pain responses similar to the pain-free group on most measures. No group differences in endogenous pain inhibition emerged. Conclusions These findings suggest that altered central processing of pain is particularly characteristic of individuals with moderate to severe symptomatic knee OA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing ...disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
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