Nodular glomerulosclerosis with anti-glomerular basement membrane-like glomerulonephritis; a distinct pattern of kidney injury observed in smokers

Background: Cigarette smoking has recently been recognized as a risk factor for developing nodular glomerulosclerosis and has also been frequently encountered in patients with anti-glomerular basement membrane (anti-GBM) disease. However, the concurrent presence of both patterns of glomerular injury has not been previously reported. Material and methods In this article, we describe three patients with non-diabetic nodular glomerulosclerosis, anti-GBM-like glomerulonephritis (GN) and a history of heavy smoking. Results: Our cohort included three patients, of which two were men (53 and 77 years old) and one a 28-year-old woman. None of the patients had a history of diabetes mellitus but all of them were heavy smokers who presented with renal insufficiency and proteinuria. Nodular glomerulosclerosis and occasional small, non-circumferential crescents in different stages of development were found on kidney biopsy. Immunofluorescence microscopy studies showed intense linear IgG staining along the glomerular basement membranes in the absence of granular immune-type deposits. Electron microscopy evaluation revealed prominent endothelial cell injury without detectable electron-dense deposits. One patient was dialysis-dependent a few months post-biopsy while the other two patients maintained their kidney function 18 and 24 months post-biopsy but without a significant improvement of serum creatinine. Conclusions: The combination of nodular glomerulosclerosis and anti-GBM-like GN appears to be a distinct pattern of injury observed in a small subset of heavy smokers. Although this pattern of glomerular injury might be less aggressive than the typical anti-GBM GN, it does not appear to carry a favorable prognosis

Analysis of the Spore Membrane Proteome in Clostridium perfringens Implicates Cyanophycin in Spore Assembly.

UnlabelledHeat-resistant endospore formation plays an important role in Clostridium perfringens-associated foodborne illnesses. The spores allow the bacterium to survive heating during normal cooking processes, followed by germination and outgrowth of the bacterium in contaminated foods. To identify proteins associated with germination and other spore functions, a comparative spore membrane proteome analysis of dormant and germinated spores of C. perfringens strain SM101 was performed by using gel-based protein separation and liquid chromatography coupled with matrix-assisted laser desorption ionization-tandem time of flight (MALDI-TOF/TOF) mass spectrometry. A total of 494 proteins were identified, and 117 of them were predicted to be integral membrane or membrane-associated proteins. Among these membrane proteins, 16 and 26 were detected only in dormant and germinated spores, respectively. One protein that was detected only in germinated spore membranes was the enzyme cyanophycinase, a protease that cleaves the polymer cyanophycin, which is composed of l-arginine-poly(l-aspartic acid), to β-Asp-Arg. Genes encoding cyanophycinase and cyanophycin synthetase have been observed in many species of Clostridium, but their role has not been defined. To determine the function of cyanophycin in C. perfringens, a mutation was introduced into the cphA gene, encoding cyanophycin synthetase. In comparison to parent strain SM101, the spores of the mutant strain retained wild-type levels of heat resistance, but fewer spores were made, and they were smaller, suggesting that cyanophycin synthesis plays a role in spore assembly. Although cyanophycin could not be extracted from sporulating C. perfringens cells, an Escherichia coli strain expressing the cphA gene made copious amounts of cyanophycin, confirming that cphA encodes a cyanophycin synthetase.ImportanceClostridium perfringens is a common cause of food poisoning, and germination of spores after cooking is thought to play a significant role in the disease. How C. perfringens controls the germination process is still not completely understood. We characterized the proteome of the membranes from dormant and germinated spores and discovered that large-scale changes occur after germination is initiated. One of the proteins that was detected after germination was the enzyme cyanophycinase, which degrades the storage compound cyanophycin, which is found in cyanobacteria and other prokaryotes. A cyanophycin synthetase mutant was constructed and found to make spores with altered morphology but normal heat resistance, suggesting that cyanophycin plays a different role in C. perfringens than it does in cyanobacteria

Efficiency of Electron-Positron Pair Productionby Neutrino Flux from Accretion Disk of a Kerr Black Hole

Dominant processes of neutrino production and neutrino-induced \ep-pair production are examined in the model of a disk hyper-accreting onto a Kerr black hole. The efficiency of plasma production by a neutrino flux from the disk, obtained for the both cases of presence and absence of a magnetic field, is found to be no more than several tenths of percent and, therefore, not enough for the origin of cosmological gamma-ray bursts.Comment: 8 pages, 1 figur

The X-ray eclipse of the dwarf nova HT CAS observed by the XMM-Newton satellite: spectral and timing analysis

A cataclysmic variable is a binary system consisting of a white dwarf that accretes material from a secondary object via the Roche-lobe mechanism. In the case of long enough observation, a detailed temporal analysis can be performed, allowing the physical properties of the binary system to be determined. We present an XMM-Newton observation of the dwarf nova HT Cas acquired to resolve the binary system eclipses and constrain the origin of the X-rays observed. We also compare our results with previous ROSAT and ASCA data. After the spectral analysis of the three EPIC camera signals, the observed X-ray light curve was studied with well known techniques and the eclipse contact points obtained. The X-ray spectrum can be described by thermal bremsstrahlung of temperature $kT_1=6.89 \pm 0.23$ keV plus a black-body component (upper limit) with temperature $kT_2=30_{-6}^{+8}$ eV. Neglecting the black-body, the bolometric absorption corrected flux is $F^{\rm{Bol}}=(6.5\pm 0.1)\times10^{-12}$ erg s$^{-1}$ cm$^{-2}$, which, for a distance of HT Cas of 131 pc, corresponds to a bolometric luminosity of $(1.33\pm 0.02)\times10^{31}$ erg s$^{-1}$. The study of the eclipse in the EPIC light curve permits us to constrain the size and location of the X-ray emitting region, which turns out to be close to the white dwarf radius. We measure an X-ray eclipse somewhat smaller (but only at a level of $\simeq 1.5 \sigma$) than the corresponding optical one. If this is the case, we have possibly identified the signature of either high latitude emission or a layer of X-ray emitting material partially obscured by an accretion disk.Comment: Accepted for publication on Astronomy and Astrophysics, 200

Hyper-Accreting Black Holes and Gamma-Ray Bursts

A variety of current models for gamma-ray bursts (GRBs) suggest a common engine - a black hole of several solar masses accreting matter from a disk at a rate 0.01 to 10 solar masses per second. Using a numerical model for relativistic disk accretion, we have studied steady-state accretion at these high rates. Inside a radius ~ 10**8 cm, for accretion rates greater than about 0.01 solar masses per second, a global state of balanced power comes to exist between neutrino losses, chiefly pair capture on nucleons, and dissipation. Energy emitted in neutrinos is less, and in the case of low accretion rates, very much less, than the maximum efficiency factor for black hole accretion (0.057 for no rotation; 0.42 for extreme Kerr rotation) times Mdot c**2. The efficiency for producing a pair fireball along the rotational axis by neutrino annihilation is calculated and found to be highly variable and very sensitive to the accretion rate. For some of the higher accretion rates studied, it can be several per cent or more; for accretion rates less than 0.05 solar masses per second, it is essentially zero. The efficiency of the Blandford-Znajek mechanism in extracting rotational energy from the black hole is also estimated. In light of these results, the viability of various gamma-ray burst models is discussed and the sensitivity of the results to disk viscosity, black hole rotation rate, and black hole mass explored. A diverse range of GRB energies seems unavoidable and neutrino annihilation in hyper-accreting black hole systems can explain bursts up to 10**52 erg. Larger energies may be inferred for beaming systems.Comment: 46 pages, includes 9 figures, LaTeX (uses aaspp4.sty), accepted by The Astrophysical Journal. Additional solutions in Tables and Figs. 4 and 5, minor revisions to text, references adde

Cohort profile: biological pathways of risk and resilience in Syrian refugee children (BIOPATH)

The BIOPATH cohort was established to explore the interplay of psychosocial and biological factors in the development of resilience and mental health problems in Syrian refugee children. Based in Lebanon, a middle-income country significantly impacted by the refugee crisis, it is the first such cohort of refugees in the Middle East. Families were recruited from informal tented settlements in the Beqaa region using purposive cluster sampling. At baseline (October 2017–January 2018), N = 3188 individuals participated [n = 1594 child–caregiver dyads; child gender, 52.6% female; mean (SD) age = 11.44 (2.44) years, range = 6–19]. Re-participation rate at 1-year follow-up was 62.8%. Individual interviews were conducted with children and primary caregivers and biological samples collected from children. Measures include: (1) children’s well-being and mental health problems (using tools validated against clinical interviews in a subsample of the cohort); (2) psychosocial risk and protective factors at the level of the individual (e.g. coping strategies), family (e.g. parent–child relationship), community (e.g. collective efficacy), and wider context (e.g. services); (3) saliva samples for genetic and epigenetic (methylation) analyses; (4) hair samples to measure cortisol, dehydroepiandrosterone (DHEA) and testosterone. This cohort profile provides details about sampling and recruitment, data collection and measures, demographic data, attrition and potential bias, key findings on resilience and mental health problems in children and strengths and limitations of the cohort. Researchers interested in accessing data should contact Professor Michael Pluess at Queen Mary University of London, UK (e-mail: [email protected]). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00127-022-02228-8

Turbulence in circumstellar disks

We investigate the analogy between circumstellar disks and the Taylor-Couette flow. Using the Reynolds similarity principle, the analogy results in a number of parameter-free predictions about stability of the disks, and their turbulent transport properties, provided the disk structure is available. We discuss how the latter can be deduced from interferometric observations of circumstellar material. We use the resulting disk structure to compute the molecular transport coefficients, including the effect of ionization by the central object. The resulting control parameter indicates that the disk is well into the turbulent regime. The analogy is also used to compute the effective accretion rate, as a function of the disk characteristic parameters (orbiting velocity, temperature and density). These values are in very good agreement with experimental, parameter-free predictions derived from the analogy. The turbulent viscosity is also computed and found to correspond to an $\alpha$-parameter $2\times 10^{-4}<\alpha<2\times 10^{-2}$. Predictions regarding fluctuations are also checked: luminosity fluctuations in disks do obey the same universal distribution as energy fluctuations observed in a laboratory turbulent flow. Radial velocity dispersion in the outer part of the disk is predicted to be of the order of 0.1 km/s, in agreement with available observations. All these issues provide a proof of the turbulent character of the circumstellar disks, as well as a parameter-free theoretical estimate of effective accretion rates.Comment: Accepted for publication in Astronomy and Astrophysics, 13 page

Advection Dominated Accretion Flows in the Kerr Metric: I. Basic Equations

We write down and solve equations describing steady state, optically thin, advection-dominated accretion onto a Kerr black hole. The mean flow, described by the relativistic fluid equations, is axisymmetric and vertically averaged. The effect of turbulence in the flow is represented by a viscous shear stress. Our treatment differs in several important ways from earlier work: we use a causal prescription for the shear stress, we do not assume the relativistic enthalpy is unity (this is important for rapidly rotating holes), and we use a relativistic equation of state. We present several representative solutions and use them to evaluate the importance of relativistic effects, to check our approximations, and to evaluate the robustness of the input physics. Detailed properties of the solutions are described in an accompanying paper.Comment: 31 pages, LaTeX, uses aaspp4.tex, includes 5 PostScript figures. Submitted to the Astrophysical Journa

Using item response theory to explore the psychometric properties of extended matching questions examination in undergraduate medical education

BACKGROUND: As assessment has been shown to direct learning, it is critical that the examinations developed to test clinical competence in medical undergraduates are valid and reliable. The use of extended matching questions (EMQ) has been advocated to overcome some of the criticisms of using multiple-choice questions to test factual and applied knowledge. METHODS: We analysed the results from the Extended Matching Questions Examination taken by 4th year undergraduate medical students in the academic year 2001 to 2002. Rasch analysis was used to examine whether the set of questions used in the examination mapped on to a unidimensional scale, the degree of difficulty of questions within and between the various medical and surgical specialties and the pattern of responses within individual questions to assess the impact of the distractor options. RESULTS: Analysis of a subset of items and of the full examination demonstrated internal construct validity and the absence of bias on the majority of questions. Three main patterns of response selection were identified. CONCLUSION: Modern psychometric methods based upon the work of Rasch provide a useful approach to the calibration and analysis of EMQ undergraduate medical assessments. The approach allows for a formal test of the unidimensionality of the questions and thus the validity of the summed score. Given the metric calibration which follows fit to the model, it also allows for the establishment of items banks to facilitate continuity and equity in exam standards

X-Ray spectra from protons illuminating a neutron star

We consider the interaction of a slowly rotating unmagnetized neutron star with a hot (ion supported, ADAF) accretion flow. The virialized protons of the ADAF penetrate into the neutron star atmosphere, heating a surface layer. Detailed calculations are presented of the equilibrium between heating by the protons, electron thermal conduction, bremsstrahlung and multiple Compton scattering in this layer. Its temperature is of the order 40-70 keV. Its optical depth increases with the incident proton energy flux, and is of the order unity for accretion at $10^{-2}$--$10^{-1}$ of the Eddington rate. At these rates, the X-ray spectrum produced by the layer has a hard tail extending to 100 keV, and is similar to the observed spectra of accreting neutron stars in their hard states. The steep gradient at the base of the heated layer gives rise to an excess of photons at the soft end of the spectrum (compared to a blackbody) through an `inverse photosphere effect'. The differences with respect to previous studies of similar problems are discussed, they are due mostly to a more accurate treatment of the proton penetration process and the vertical structure of the heated layer.Comment: Accepted for publication in A&