Distillation of 56^{56}Fe in Ultramassive O-Ne White Dwarfs

When white dwarfs freeze the plasma mixtures inside them undergo separation processes which can produce radical changes in the composition profile of the star. The abundance of neutron rich elements, such as $^{22}$Ne or $^{56}$Fe, determines whether or not the first crystals are more or less dense than the surrounding fluid and thus whether they sink or float. These processes have now been studied for C-O-Ne and C-O-Fe mixtures, finding that distillation and precipitation processes are possible in white dwarfs. In this work, we calculate the phase diagram of more complicated O-Ne-Fe mixtures and make predictions for the internal structure of the separated white dwarf. There are two possible outcomes determined by a complicated interplay between the Ne abundance, the $^{22}$Ne fraction, and the $^{56}$Fe abundance. Either Fe distills to form an inner core because the first O-Ne solids are buoyant, or an O-Ne inner core forms and Fe accumulates in the liquid until Fe distillation begins and forms a Fe shell. In the case of an Fe shell, a Rayleigh-Taylor instability may arise and overturn the core. In either case, Fe distillation may only produce a cooling delay of order 0.1 Gyr as these processes occur early at high white dwarf luminosities. Fe inner cores and shells may be detectable through asteroseismology and could enhance the yield of neutron rich elements such as $^{55}$Mn and $^{58}$Ni in supernovae.Comment: 8 pages, 3 figures, accepted for publication in Ap

Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors

PURPOSE: Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T-cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune-related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD-L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD-L1 in pituitary adenomas. METHODS: PD-L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non-functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. RESULTS: Pituitary tumors express variable levels of PD-L1 transcript and protein. PD-L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin-expressing) pituitary adenomas compared to non-functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD-L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD-L1 expression, particularly in the functional subtypes. CONCLUSIONS: Human pituitary adenomas harbor PD-L1 across subtypes, with significantly higher expression in functioning adenomas compared to non-functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management

Leukotriene antagonists as first-line or add-on asthma controller therapy

Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score =6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score =1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group

Bovine tuberculosis epidemiology in Cameroon, Central Africa, based on the interferon gamma assay

Despite sub-Saharan Africa (SSA) accounting for ~20% of the global cattle population, prevalence estimates and related risk factors of bovine tuberculosis (bTB) are still poorly described. The increased sensitivity of the IFN-γ assay and its practical benefits suggest the test could be useful to investigate bTB epidemiology in SSA. This study used a population-based sample to estimate bTB prevalence, identify risk factors and estimate the effective reproductive rate in Cameroonian cattle populations. A cross-sectional study was conducted in the North West Region (NWR) and the Vina Division (VIN) of Cameroon in 2013. A regional stratified sampling frame of pastoral cattle herds produced a sample of 1,448 cattle from 100 herds. In addition, a smaller cross-sectional study sampled 60 dairy cattle from 46 small-holder co-operative dairy farmers in the NWR. Collected blood samples were stimulated with bovine and avian purified protein derivatives, with extracted plasma screened using the IFN-γ enzyme-linked immunosorbent assay (Prionics Bovigam®). Design-adjusted population prevalences were estimated, and multivariable mixed-effects logistic regression models using Bayesian inference techniques identified the risk factors for IFN-γ positivity. Using the IFN-γ assay, the prevalence of bTB in the dairy cattle was 21.7% (95% CI: 11.2–32.2). The design-adjusted prevalence of bTB in cattle kept by pastoralists was 11.4% (95% CI: 7.6–17.0) in the NWR and 8.0% (95% CI: 4.7–13.0) in the VIN. A within-herd prevalence estimate for pastoralist cattle also supported that the NWR had higher prevalence herds than the VIN. Additionally, the estimates of the effective reproductive rate Rt were 1.12 for the NWR and 1.06 for the VIN, suggesting different transmission rates within regional cattle populations in Cameroon. For pastoral cattle, an increased risk of IFN-γ assay positivity was associated with being male (OR = 1.89; 95% CI:1.15–3.09), increasing herd size (OR = 1.02; 95% CI:1.01–1.03), exposure to the bovine leucosis virus (OR = 2.45; 95% CI: 1.19–4.84) and paratuberculosis (OR = 9.01; 95% CI: 4.17–20.08). Decreased odds were associated with contacts at grazing, buffalo (OR = 0.20; 95% CI: 0.03–0.97) and increased contact with other herds [1–5 herds: OR = 0.16 (95% CI: 0.04–0.55); 6+ herds: OR = 0.18 (95% CI: 0.05–0.64)]. Few studies have used the IFN-γ assay to describe bTB epidemiology in SSA. This study highlights the endemic situation of bTB in Cameroon and potential public health risks from dairy herds. Further work is needed to understand the IFN-γ assay performance, particularly in the presence of co-infections, and how this information can be used to develop control strategies in the SSA contexts

Extensions of the matrix Gelfand-Dickey hierarchy from generalized Drinfeld-Sokolov reduction

The $p\times p$ matrix version of the $r$-KdV hierarchy has been recently treated as the reduced system arising in a Drinfeld-Sokolov type Hamiltonian symmetry reduction applied to a Poisson submanifold in the dual of the Lie algebra $\widehat{gl}_{pr}\otimes {\Complex}[\lambda, \lambda^{-1}]$. Here a series of extensions of this matrix Gelfand-Dickey system is derived by means of a generalized Drinfeld-Sokolov reduction defined for the Lie algebra $\widehat{gl}_{pr+s}\otimes {\Complex}[\lambda,\lambda^{-1}]$ using the natural embedding $gl_{pr}\subset gl_{pr+s}$ for $s$ any positive integer. The hierarchies obtained admit a description in terms of a $p\times p$ matrix pseudo-differential operator comprising an $r$-KdV type positive part and a non-trivial negative part. This system has been investigated previously in the $p=1$ case as a constrained KP system. In this paper the previous results are considerably extended and a systematic study is presented on the basis of the Drinfeld-Sokolov approach that has the advantage that it leads to local Poisson brackets and makes clear the conformal ($\cal W$-algebra) structures related to the KdV type hierarchies. Discrete reductions and modified versions of the extended $r$-KdV hierarchies are also discussed.Comment: 60 pages, plain TE

Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; Toward Robust Point-of-Care Detection

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid "photochemical fingerprinting"approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device.</p

Photochemical fingerprinting is a sensitive probe for the detection of synthetic cannabinoid receptor agonists; towards robust point-of-care detection

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid “photochemical fingerprinting” approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device

The HIPASS Catalogue - II. Completeness, Reliability, and Parameter Accuracy

The HI Parkes All Sky Survey (HIPASS) is a blind extragalactic HI 21-cm emission line survey covering the whole southern sky from declination -90 to +25. The HIPASS catalogue (HICAT), containing 4315 HI-selected galaxies from the region south of declination +2, is presented in Meyer et al. (2004a, Paper I). This paper describes in detail the completeness and reliability of HICAT, which are calculated from the recovery rate of synthetic sources and follow-up observations, respectively. HICAT is found to be 99 per cent complete at a peak flux of 84 mJy and an integrated flux of 9.4 Jy km/s. The overall reliability is 95 per cent, but rises to 99 per cent for sources with peak fluxes >58 mJy or integrated flux > 8.2 Jy km/s. Expressions are derived for the uncertainties on the most important HICAT parameters: peak flux, integrated flux, velocity width, and recessional velocity. The errors on HICAT parameters are dominated by the noise in the HIPASS data, rather than by the parametrization procedure.Comment: Accepted for publication in MNRAS. 12 pages, 11 figures. Paper with higher resolution figures can be downloaded from http://hipass.aus-vo.or

Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays

Background: We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism) microarrays and DNA pooling (SNP-MaP) employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations). The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes. Findings: In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods. Conclusions: Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred