Disk emission and atmospheric absorption lines in black hole candidate 4U 1630-472

We re-analyzed SUZAKU data of the black hole candidate 4U 1630-472 being in the high/soft state. We show that the continuum X-ray spectrum of 4U 1630-472 with iron absorption lines can be satisfactorily modeled by the spectrum from an accretion disk atmosphere. Absorption lines of highly ionized iron originating in hot accretion disk atmosphere can be an alternative or complementary explanation to the wind model usually favored for these type of sources. We model continuum and line spectra using a single model. Absorption lines of highly ionized iron can origin in upper parts of the disk atmosphere which is intrinsically hot due to high disk temperature. Iron line profiles computed with natural, thermal and pressure broadenings match very well observations. We showed that the accretion disk atmosphere can effectively produce iron absorption lines observed in 4U 1630-472 spectrum. Absorption line arising in accretion disk atmosphere is the important part of the observed line profile, even if there are also other mechanisms responsible for the absorption features. Nevertheless, the wind theory can be an artifact of the fitting procedure, when the continuum and lines are fitted as separate model components.Comment: 10 pages, 4 figures, accepted by Astronomy and Astrophysic

Clinical characteristics in subjects with NLRP3 V198M diagnosed at a single UK center and a review of the literature

INTRODUCTION: Mutations in the NLRP3 gene are associated with the dominantly inherited cryopyrin-associated periodic syndrome (CAPS). The significance of the V198M variant is unclear; it has been reported in association with various CAPS phenotypes and as a variant of uncertain consequence. The aim of this study was to characterize the clinical phenotypes and treatments in individuals with V198M assessed in a single UK center. METHODS: DNA samples from 830 subjects with fever syndromes or a family history of CAPS were screened for mutations in the NLRP3 gene with polymerase chain reaction (PCR) and sequencing. A detailed medical history was available in all cases. Inflammatory disease activity was monitored monthly with measurements of serum amyloid A protein (SAA) and C-reactive protein (CRP) in symptomatic individuals. RESULTS: NLRP3 V198M was identified in 19 subjects. It was found in association with CAPS in five cases, in one patient with Schnitzler syndrome, in three patients who also had a nucleotide alteration in another fever gene, and in three other patients with evidence of an autoinflammatory phenotype. Seven asymptomatic individuals were detected during screening of family members. CONCLUSIONS: The NLRP3 V198M variant shows variable expressivity and reduced penetrance. It may be associated with classical inherited or apparently sporadic CAPS and with atypical autoinflammatory disease of varying severity, intriguingly including Schnitzler syndrome. The factors that influence the pathogenic consequences of this variant remain unknown. However, the remarkable response to interleukin 1 (IL-1) blockade in all but one individual in our series confirms that their clinical features are indeed mediated by IL-1

Brief Report: Association of Tumor Necrosis Factor Receptor–Associated Periodic Syndrome With Gonosomal Mosaicism of a Novel 24-Nucleotide TNFRSF1A Deletion

Objective: To investigate the molecular cause of persistent fevers in a patient returning from working overseas, in whom investigations for tropical diseases yielded negative results. / Methods: DNA was extracted from the patient's whole blood, leukocyte subpopulations, saliva, hair root, and sperm. The TNFRSF1A gene was analyzed by polymerase chain reaction (PCR), allele-specific PCR, Sanger sequencing, and next-generation sequencing. In silico molecular modeling was performed to predict the structural and functional consequences of the tumor necrosis factor receptor (TNFR) type I protein mutation in the extracellular domain. / Results: Sanger sequencing corroborated by allele-specific PCR detected a novel in-frame deletion of 24 nucleotides (c.255_278del) in the TNFRSF1A gene, and this was subsequently confirmed using next-generation sequencing methods (targeted sequencing and amplicon-based deep sequencing). Results of amplicon-based deep sequencing revealed variable frequency of the mutant allele among different cell lines, including sperm, thus supporting the presence of gonosomal TNFRSF1A mosaicism. The patient had a complete response to treatment with interleukin-1 (IL-1) blockade, with resolution of symptoms and normalization of acute-phase protein levels. / Conclusion: We describe the first case of gonosomal TNFRSF1A mosaicism in a patient with TNFR-associated periodic syndrome (TRAPS), which was attributable to a novel, somatic 24-nucleotide in-frame deletion. The clinical picture in this patient, including the complete response to IL-1 blockade, was typical of that found in TRAPS. This case adds TRAPS to the list of dominantly inherited autoinflammatory diseases reported to be caused by somatic (or postzygotic) mutation

Molecular genetic investigation, clinical features and response to treatment in 21 patients with Schnitzler's syndrome

To date, the pathogenic mechanisms underlying Schnitzler syndrome remain obscure, in particular, the interplay between the monoclonal protein and increased interleukin-1β (IL-1β) production, although interest in the contribution of genetic factors has been fueled by detection of somatic NLRP3 mosaicism in 2 patients with the variant-type Schnitzler syndrome. At 2 specialist UK centers, we have identified 21 patients who fulfilled diagnostic criteria for Schnitzler syndrome with urticarial rash, fever, arthralgia, and bone pain; 47% reported weight loss, 40% fatigue, and 21% lymphadenopathy. An immunoglobulin M (IgM) κ paraprotein was detected in 86%; the remainder had IgM λ or IgG κ. Patients underwent searches for germ line and somatic mutations using next-generation sequencing technology. Moreover, we designed a panel consisting of 32 autoinflammatory genes to explore genetic susceptibility factor(s) to Schnitzler syndrome. Genetic analysis revealed neither germ line nor somatic NLRP3, TNFRSF1A, NLRC4, or NOD2 mutations, apart from 1 patient with a germ line NLRP3 p.V198M substitution. The proinflammatory cytokines and extracellular apoptosis-associated speck-like protein with caspase recruitment domain (ASC) measured in the serum of Schnitzler syndrome patients during active disease were significantly higher than healthy controls. Ninety-five percent of our cohort achieved a complete response to recombinant IL-1 receptor antagonist (anakinra). Our findings do not support a role for somatic NLRP3 mosaicism in disease pathogenesis; although elevated levels of ASC, IL-6, and IL-18 in patients’ serum, and the response to anakinra, suggest that Schnitzler syndrome is associated with upregulated inflammasome activation. Despite its rarity, Schnitzler syndrome is an important diagnosis as treatment with IL-1 antagonists dramatically improves quality of life for patients

What did we achieve with VALITEST an EU project on validation in plant pest diagnostics?

peer reviewedEnsuring the reliability of diagnostic activities is an essential cornerstone of Plant Health strategies to reduce the risk of entry and spread of plant pests in a region and ultimately their impacts. Diagnostic tests should be validated to ensure that they are fit for purpose. Validation is usually done by diagnostic laboratories although companies commercializing diagnostic kits also produce validation data for their products. Due to the high number of pest , matrix and method combinations and given the significant resources required to validate tests, it is essential that validation data are shared with the entire diagnostic community and produced in a harmonized way to facilitate their use by different stakeholders. Indeed, the selection of tests to be used in specific contexts is not the sole responsibility of diagnostic laboratories and also involve National Plant Protection Organizations. The VALITEST EU project (2018-2021) was established to tackle all these issues. New validation data for tests targeting important pests for the EPPO region were produced. Guidelines to improve and harmonize the validation framework were developed. Sharing of validation data and experience was ensured through the development of new or existing databases, the organization of training courses and the dissemination of the project outputs in scientific publications and Standards. Finally, the involvement of researchers, diagnosticians, policy makers, inspectors, industries etc. and the establishment of the European Plant Diagnostic Industry Association were important actions to strengthen the interactions between Plant Health stakeholders

ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in three infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALKrearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (seven and twelve from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated-ERK, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, while CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, ten with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis, and provides guidance for the clinical management of this emerging histiocytic entity.Molecular tumour pathology - and tumour genetic

Modelling nutrient transport in Currency Creek, NSW with AnnAGNPS and PEST

The modelling package Annualized Agricultural Nonpoint Source Model (AnnAGNPS) was applied to the prediction of export of nitrogen and phosphorus from Currency Creek, a small experimental catchment within the Hawkesbury–Nepean drainage basin of the Sydney Region. The catchment is 255 ha in area and has experienced extensive soil erosion and losses of nutrients from intensive vegetable cultivation, irrigated dairy pasture and poultry farms. Simulations of nitrogen and phosphorus loads in the Currency Creek catchment were performed at various temporal scales and the degree of calibration was quantified by comparing the simulated data with the monitoring results. In addition, the model independent, nonlinear parameter estimation code PEST, was applied for sensitivity testing to determine and assess the relative importance of the key parameters of the model. Event flows were simulated satisfactorily with AnnAGNPS but only moderate accuracy was achieved for prediction of event-based nitrogen and phosphorus exports. The biggest deviations from the measured data were observed for daily simulations but trends in the generated nutrients matched observed data. Despite achieving good resemblance between measured and predicted phosphorus loads the model showed high level of sensitivity to assigned pH values for topsoil. Increase in pH by one unit resulted in up to 34% increase in model generated particulate phosphorus load

Farm-scale stormwater losses of sediment and nutrients from a market garden near Sydney, Australia

Agricultural runoff contributes to water quality problems in the Hawkesbury–Nepean River near Sydney, Australia. This paper presents a case study of sediment, nitrogen (N) and phosphorus (P) losses from a market garden in the Hawkesbury–Nepean catchment. Event-based runoff sampling and flow and rainfall monitoring were carried out at the boundary of an 8-ha commercial market garden near Richmond, NSW, over two years (1995–1997). A record of fertiliser use and soil management was compiled during the runoff monitoring period. Soil management practices were similar to other market gardens on duplex soils in the area. Farm practices were consistent with ‘traditional’ industry practices. Over the 2-year period, stormwater runoff losses from the farm were equivalent to 19 t ha−1 per year of suspended sediment, 11 kg of P ha−1 per year, and 127 kg of N ha−1 per year. Sixty percent of soil loss occurred in summer (December, January and February), reflecting both seasonal climatic changes and soil management practices. Soil erosion was the major mechanism for P mobilisation and transport; however, a significant increase in the event mean concentration (EMC) of soluble P was observed over the 2 years. During this period, we measured an increase in extractable soil P (Bray) in surface soil from 174 to 304 mg kg−1 and a concomitant decrease in P sorption. The highest concentrations of N in runoff occurred after applications of poultry manure and during an extensive fallow period (late spring through to the end of summer). The results show that, in the Sydney region, market gardening on duplex soils using traditional practices is environmentally unsustainable, and may provide economic incentive to bring about change