Naresuan University Journal
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Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy: A Mimic of Childhood Granulomatosis With Polyangiitis.
No full textIMPORTANCE: The type I interferonopathies comprise a recently recognized group of mendelian diseases characterized by an upregulation of type I interferon signaling. These monogenic phenotypes include classic Aicardi-Goutières syndrome and syndromic forms of systemic lupus erythematosus, including familial chilblain lupus and spondyloenchondrodysplasia. Dermatologic features provide a major diagnostic clue to this disease grouping, as exemplified by the recently described stimulator of interferon genes-associated vasculopathy with onset in infancy (SAVI) caused by gain-of-function mutations in TMEM173. OBSERVATIONS: We describe a male child who, from the age of 2 months, had significant cutaneous disease that manifested as red violaceous plaques of the cheeks, nose, ears, fingers, and toes that progressed to gangrenous necrosis. In addition to his severe cutaneous vasculopathy, he experienced recurrent fevers, interstitial lung disease, and failure to thrive. His clinical syndrome was refractory to multiple immunosuppressive therapies. Evidence of marked upregulation of type I interferon signaling was observed in peripheral blood, and genetic testing identified a de novo germline mutation in TMEM173, confirming a diagnosis of SAVI 7 years after the onset of his disease. CONCLUSIONS AND RELEVANCE: This observational report describes a new case of SAVI, a recently defined monogenic inflammatory phenotype, that exemplifies an emerging group of disorders related to primary upregulation of type I interferon signaling
Negative emotions towards others are diminished in remitted major depression
No full textBACKGROUND: One influential view is that vulnerability to major depressive disorder (MDD) is associated with a proneness to experience negative emotions in general. In contrast, blame attribution theories emphasise the importance of blaming oneself rather than others for negative events. Our previous exploratory study provided support for the attributional hypothesis that patients with remitted MDD show no overall bias towards negative emotions, but a selective bias towards emotions entailing self-blame relative to emotions that entail blaming others. More specifically, we found a decreased proneness for contempt/disgust towards others relative to oneself (i.e. self-contempt bias). Here, we report a definitive test of the competing general negative versus specific attributional bias theories of MDD. METHODS: We compared a medication-free remitted MDD (n=101) and a control group (n=70) with no family or personal history of MDD on a previously validated experimental test of moral emotions. The task measures proneness to specific emotions associated with different types of self-blame (guilt, shame, self-contempt/disgust, self-indignation/anger) and blame of others (other-indignation/anger, other-contempt/disgust) whilst controlling for the intensity of unpleasantness. RESULTS: We confirmed the hypothesis that patients with MDD exhibit an increased self-contempt bias with a reduction in contempt/disgust towards others. Furthermore, they also showed a decreased proneness for indignation/anger towards others. CONCLUSIONS: This corroborates the prediction that vulnerability to MDD is associated with an imbalance of specific self- and other-blaming emotions rather than a general increase in negative emotions. This has important implications for neurocognitive models and calls for novel focussed interventions to rebalance blame in MDD
UManSysProp: an online facility for molecular property prediction and atmospheric aerosol calculations
No full textIn this paper we describe the development and application of a new web based facility, UManSysProp (http://umansysprop.seaes.manchester.ac.uk), for automating predictions of molecular and atmospheric aerosol properties. Current facilities include: pure component vapour pressures, critical properties and sub-cooled densities of organic molecules; activity coefficient predictions for mixed inorganic–organic liquid systems; hygroscopic growth factors and CCN activation potential of mixed inorganic/organic aerosol particles; absorptive partitioning calculations with/without a treatment of non-ideality. The aim of this new facility is to provide a single point of reference for all properties relevant to atmospheric aerosol that have been checked for applicability to atmospheric compounds where possible. The group contribution approach allows users to upload molecular information in the form of SMILES strings and UManSysProp will automatically extract the relevant information for calculations. Built using open source chemical informatics, and hosted at the University of Manchester, the facilities are provided via a browser and device-friendly web-interface, or can be accessed using the user's own code via a JSON API. In this paper we demonstrate its use with specific examples that can be simulated using the web-browser interface
The mapping and differentiation of biological and environmental elemental signatures in the fossil remains of a 50 million year old bird
No full textThe preservation of fossils reflects the interplay of inorganic and organic chemical processes, which should be clearly differentiated to make interpretations about the biology of extinct organisms. A new coliiformes bird (mouse bird) from the [similar]50 million year old Green River Formation (Wyoming, USA) has here been analysed using synchrotron X-ray fluorescence and environmental scanning electron microscopy with an attached X-ray energy dispersive system (ESEM-EDS). The concentration and distribution of 16 elements (Si, P, S, Cl, K, Ca, Ti, Mg, Fe, Ni, Cu, Zn, As, Br, Ba, Hg) has been mapped for individual points on the sample. S, Cu and Zn map distinctly within visibly preserved feathers and X-ray Absorption Spectroscopy (XAS) shows that S and Cu within the feathers are organically bound in a similar manner to modern feathers. The morphological preservation of the feathers, on both macro- and microscopic scales, is variable throughout the fossil and the differences in the lateral microfacies have resulted in a morphological preservation gradient. This study clearly differentiates endogenous organic remains from those representing exogenous overprinted geochemical precipitates and illustrates the chemical complexity of the overall taphonomic process
Non-pharmacological interventions aimed at modifying health and behavioural outcomes for adults with asthma: a critical review.
No full textAllergen-induced early and late asthmatic responses to inhaled seasonal and perennial allergens.
No full textBACKGROUND: The allergen bronchoprovocation test (ABP) is a validated model to study asthma pathophysiology and response to treatments. The inhibitory effect of agents on the allergen-induced late asthmatic response (LAR) is a predictor of their efficacy in asthma treatment. However, it is difficult to predict the magnitude of a LAR, which may vary according to immune responsiveness and the type of allergen used for ABP. AIM: To determine the relationship between the magnitudes of EAR and LAR in mild asthmatic subjects according to the type of allergen inhaled, and its determinants. METHODS: This is a retrospective analysis of a large database of ABPs, all performed with a common standardized methodology. Patients were either challenged with house-dust mites (HDM), animals, or pollens. EAR was defined as a ≥20% fall in forced expiratory volume in one second (FEV1
Mass spectrometric imaging of brain tissue by time-of-flight secondary ion mass spectrometry – How do polyatomic primary beams C60+, Ar2000+, water-doped Ar2000+ and (H2O)6000+ compare?
No full textRationale To discover the degree to which water-containing cluster beams increase secondary ion yield and reduce the matrix effect in time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging of biological tissue. Methods The positive SIMS ion yields from model compounds, mouse brain lipid extract and mouse brain tissue together with mouse brain images were compared using 20 keV C60+, Ar2000+, water-doped Ar2000+ and pure (H2O)6000+ primary beams. Results Water-containing cluster beams where the beam energy per nucleon (E/nucleon) ≈ 0.2 eV are optimum for enhancing ion yields dependent on protonation. Ion yield enhancements over those observed using Ar2000+ lie in the range 10 to >100 using the (H2O)6000+ beam, while with water-doped (H2O)Ar2000+ they lie in the 4 to 10 range. The two water-containing beams appear to be optimum for tissue imaging and show strong evidence of increasing yields from molecules that experience matrix suppression under other primary beams. Conclusions The application of water-containing primary beams is suggested for biological SIMS imaging applications, particularly if the beam energy can be raised to 40 keV or higher to further increase ion yield and enhance spatial resolution to ≤1 µm. © 2015 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd
Standards for Non-therapeutic Infant Male Circumcision in the Community
No full textPurposeTo produce a concise set of standards for good quality practice of non-therapeutic infant male circumcision in a community setting. Materials and MethodsAn expert panel reviewed a number sources including; existing guidelines for performing the procedure, evidence of good practice, evidence of current local provision, evidence of complications presenting to secondary care locally and from the literature, and issues of concern raised by parents, clinicians and safeguarding professionals. The panel consisted of: a Paediatric Urologist, Independent Safeguarding Children Board Chair, Director of Public Health, Consultant in Public Health, and a General Practitioner. Based on the evidence and their experience, the panel described the standards they would expect of a good quality provider performing non-therapeutic circumcision in a community clinic for boys under 12 months of age.ResultsThe panel has produced a set of 12 defined, measurable indicators that describe good quality practice for non-therapeutic infant male circumcision in the community setting. ConclusionsThe Greater Manchester Standards for infant male circumcision can be used by practitioners for self-assessment and audit purposes. The standards also allow assessment the quality of providers by parents, clinicians, public health and safeguarding professionals
