Time dependent numerical model for the emission of radiation from relativistic plasma

We describe a numerical model constructed for the study of the emission of radiation from relativistic plasma under conditions characteristic, e.g., to gamma-ray bursts (GRB's) and active galactic nuclei (AGN's). The model solves self consistently the kinetic equations for e^\pm and photons, describing cyclo-synchrotron emission, direct Compton and inverse Compton scattering, pair production and annihilation, including the evolution of high energy electromagnetic cascades. The code allows calculations over a wide range of particle energies, spanning more than 15 orders of magnitude in energy and time scales. Our unique algorithm, which enables to follow the particle distributions over a wide energy range, allows to accurately derive spectra at high energies, >100 \TeV. We present the kinetic equations that are being solved, detailed description of the equations describing the various physical processes, the solution method, and several examples of numerical results. Excellent agreement with analytical results of the synchrotron-SSC model is found for parameter space regions in which this approximation is valid, and several examples are presented of calculations for parameter space regions where analytic results are not available.Comment: Minor changes; References added, discussion on observational status added. Accepted for publication in Ap.

Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis

Aims: Congo red staining of an endomyocardial biopsy is the diagnostic gold-standard in suspected cardiac amyloidosis (CA), but the procedure is associated with the risk, albeit small, of serious complications, and delay in diagnosis due to the requirement for technical expertise. In contrast, abdominal fat pad fine needle aspiration (FPFNA) is a simple, safe and well-established procedure in systemic amyloidosis, but its diagnostic sensitivity in patients with suspected CA remains unclear. Methods and results: We assessed the diagnostic sensitivity of FPFNA in 600 consecutive patients diagnosed with CA [216 AL amyloidosis, 113 hereditary transthyretin (ATTRm), and 271 wild-type transthyretin (ATTRwt) amyloidosis] at our Centre. Amyloid was detected on Congo red staining of FPFNAs in 181/216 (84%) patients with cardiac AL amyloidosis, including 100, 97, and 78% of those with a large, moderate, and small whole-body amyloid burden, respectively, as assessed by serum amyloid P (SAP) component scintigraphy (P < 0.001); the deposits were successfully typed as AL by immunohistochemistry in 102/216 (47%) cases. Amyloid was detected in FPFNAs of 51/113 (45%) patients with ATTRm CA, and only 42/271 (15%) cases with ATTRwt CA. Conclusions: FPFNA has reasonable diagnostic sensitivity in cardiac AL amyloidosis, particularly in patients with a large whole-body amyloid burden. Although the diagnostic sensitivity of FPFNA is substantially lower in transthyretin CA, particularly ATTRwt, it may nevertheless sometimes obviate the need for endomyocardial biopsy

NiO gas sensing element prepared on needle-shaped silicon substrate

Abstract This study presents a new approach to enhancing the gas sensor properties based on increasing the sensing area by a structured substrate. Two types of needle-shaped silicon substrates with surface areas of 40 and 14 μm 2 were used as substrate for the preparation of NiO gas sensing element with a thickness of 25 nm. The surface morphology and composition of the prepared samples were examined by SEM, FIB-SEM, and GD OES methods. Deposited NiO films were continuous consisting of an agglomeration of small nanosized grains with arbitrary forms created on each Si needle. It was found that NiO had a polycrystalline nature. The gas sensing measurements revealed that hydrogen responses were better for NiO sensing elements prepared on needle-shape Si substrates with 40 μm 2 surface area than those with 14 μm 2 for all investigated concentrations and temperatures. The maximum relative sensitivity of 26% was measured at 250 ppm of hydrogen

Distribution of interneurons in the CA2 region of the rat hippocampus.

The CA2 region of the mammalian hippocampus is a unique region with its own distinctive properties, inputs and pathologies. Disruption of inhibitory circuits in this region appears to be linked with the pathology of specific psychiatric disorders, promoting interest in its local circuitry, its role in hippocampal function and its dysfunction in disease. In previous studies, CA2 interneurons, including a novel subclass of CA2 dendrite-preferring interneurons that has not been identified in other CA regions, have been shown to display physiological, synaptic and morphological properties unique to this sub-field and may therefore play a crucial role in the hippocampal circuitry. The distributions of immuno-labeled interneurons in dorsal CA2 were studied and compared with those of interneurons in CA1 and CA3. Like those in CA1 and CA3, the somata of CA2 parvalbumin-immunoperoxidase-labeled interneurons were located primarily in Stratum Pyramidale (SP) and Stratum Oriens (SO), with very few cells in Stratum Radiatum (SR) and none in Stratum Lacunosum Moleculare (SLM). There was, however, a greater proportion of GAD-positive cells were immunopositive for PV in SP in CA2 than in CA1 or CA3. CA2 SP also contained a larger density of somatostatin-, calbindin-, and VIP-immunopositive somata than CA1 and/or CA3. Like those in CA1 and CA3, CCK-immunopositive somata in CA2 were mostly located in SR. Reelin- and NPY- immunolabeled cell bodies were located in all layers of the three CA regions. However, a higher density of Reelin-positive somata was found in SP and SR of CA2 than in CA1 or CA3

Effect of covid-19 lockdown on child protection medical assessments:a retrospective observational study in Birmingham, UK

Objectives To determine any change in referral patterns and outcomes in children (0–18) referred for child protection medical examination (CPME) during the COVID-19 pandemic compared with previous years.Design Retrospective observational study, analysing routinely collected clinical data from CPME reports in a rapid response to the pandemic lockdown.Setting Birmingham Community Healthcare NHS Trust, which provides all routine CPME for Birmingham, England, population 1.1 million including 288 000 children.Participants Children aged under 18 years attending CPME during an 18-week period from late February to late June during the years 2018–2020.Main outcome measures Numbers of referrals, source of disclosure and outcomes from CPME.Results There were 78 CPME referrals in 2018, 75 in 2019 and 47 in 2020, this was a 39.7% (95% CI 12.4% to 59.0%) reduction in referrals from 2018 to 2020, and a 37.3% (95% CI 8.6% to 57.4%) reduction from 2019 to 2020. There were fewer CPME referrals initiated by school staff in 2020, 12 (26%) compared with 36 (47%) and 38 (52%) in 2018 and 2019, respectively. In all years 75.9% of children were known to social care prior to CPME, and 94% of CPME concluded that there were significant safeguarding concerns.Conclusions School closure due to COVID-19 may have harmed children as child abuse has remained hidden. There needs to be either mandatory attendance at schools in future or viable alternatives found. There may be a significant increase in safeguarding referrals when schools fully reopen as children disclose the abuse they have experienced at home

Diagnostic amyloid proteomics: experience of the UK National Amyloidosis Centre

Systemic amyloidosis is a serious disease which is caused when normal circulating proteins misfold and aggregate extracellularly as insoluble fibrillary deposits throughout the body. This commonly results in cardiac, renal and neurological damage. The tissue target, progression and outcome of the disease depends on the type of protein forming the fibril deposit, and its correct identification is central to determining therapy. Proteomics is now used routinely in our centre to type amyloid; over the past 7 years we have examined over 2000 clinical samples. Proteomics results are linked directly to our patient database using a simple algorithm to automatically highlight the most likely amyloidogenic protein. Whilst the approach has proved very successful, we have encountered a number of challenges, including poor sample recovery, limited enzymatic digestion, the presence of multiple amyloidogenic proteins and the identification of pathogenic variants. Our proteomics procedures and approaches to resolving difficult issues are outlined

Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence

Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in sixteen patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA-IV signal sequence residues (p.18–43 to p.20–43) in 16/24 trypsin-digested amyloid deposits, but in only 1/266 non-ApoA-IV amyloid samples examined. These additional signal residues were also detected in the cardiac sample from the Swedish patient in which ApoA-IV amyloid was first described, and in plasma from a single cardiac ApoA-IV amyloidosis patient. The most common signal-containing peptide observed in ApoA-IV amyloid, p.20–43 and to far lesser extent the N-terminal peptide, p.21–43 were fibrillogenic in vitro at physiological pH generating Congo red positive fibrils. The addition of a single signal-derived alanine residue to the N-terminus has resulted in markedly increased fibrillogenesis. If this effect translates to the mature circulating protein in vivo, then the presence of signal may result in preferential deposition as amyloid, perhaps acting as seed for the main circulating native form of the protein; it may also influence other ApoA-IV associated pathologies

Plasmin activity promotes amyloid deposition in a transgenic model of human transthyretin amyloidosis

Cardiac ATTR amyloidosis, a serious but much under-diagnosed form of cardiomyopathy, is caused by deposition of amyloid fibrils derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood and informative in vivo models have proved elusive. Here we report the generation of a mouse model of cardiac ATTR amyloidosis with transgenic expression of human TTRS52P. The model is characterised by substantial ATTR amyloid deposits in the heart and tongue. The amyloid fibrils contain both full-length human TTR protomers and the residue 49-127 cleavage fragment which are present in ATTR amyloidosis patients. Urokinase-type plasminogen activator (uPA) and plasmin are abundant within the cardiac and lingual amyloid deposits, which contain marked serine protease activity; knockout of α2-antiplasmin, the physiological inhibitor of plasmin, enhances amyloid formation. Together, these findings indicate that cardiac ATTR amyloid deposition involves local uPA-mediated generation of plasmin and cleavage of TTR, consistent with the previously described mechano-enzymatic hypothesis for cardiac ATTR amyloid formation. This experimental model of ATTR cardiomyopathy has potential to allow further investigations of the factors that influence human ATTR amyloid deposition and the development of new treatments

Clinical ApoA-IV amyloid is associated with fibrillogenic signal sequence

Apolipoprotein A-IV amyloidosis is an uncommon form of the disease normally resulting in renal and cardiac dysfunction. ApoA-IV amyloidosis was identified in 16 patients attending the National Amyloidosis Centre and in eight clinical samples received for histology review. Unexpectedly, proteomics identified the presence of ApoA-IV signal sequence residues (p.18-43 to p.20-43) in 16/24 trypsin-digested amyloid deposits but in only 1/266 non-ApoA-IV amyloid samples examined. These additional signal residues were also detected in the cardiac sample from the Swedish patient in which ApoA-IV amyloid was first described, and in plasma from a single cardiac ApoA-IV amyloidosis patient. The most common signal-containing peptide observed in ApoA-IV amyloid, p.20-43, and to a far lesser extent the N-terminal peptide, p.21-43, were fibrillogenic in vitro at physiological pH, generating Congo red-positive fibrils. The addition of a single signal-derived alanine residue to the N-terminus has resulted in markedly increased fibrillogenesis. If this effect translates to the mature circulating protein in vivo, then the presence of signal may result in preferential deposition as amyloid, perhaps acting as seed for the main circulating native form of the protein; it may also influence other ApoA-IV-associated pathologies. \ua9 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland