A simplified method for thermal analysis of a cowl leading edge subject to intense local shock-wave-interference heating

Type IV shock wave interference heating on a blunt body causes extremely intense heating over a very localized region of the body. An analytical solution is presented to a heat transfer problem that approximates the shock wave interference heating of an engine cowl leading edge of the National Aero-Space Plane. The problem uses a simplified geometry to represent the leading edge. An analytical solution is developed that provides a means for approximating maximum temperature differences between the outer and inner surface temperatures of the leading edge. The solution is computationally efficient and, as a result, is well suited for conceptual and preliminary design or trade studies. Transient and steady state analyses are conducted, and results obtained from the analytical solution are compared with results of 2-D thermal finite element analyses over a wide range of design parameters. Isotropic materials as well as laminated composite materials are studied. Results of parametric studies are presented to indicate the effects of the thickness of the cowl leading edge and the width of the region heated by the shock wave interference on the thermal response of the leading edge

Bullous Pemphigoid with Excoriation Disorder in a 59 Year Old Woman

Bullous pemphigoid is the most common autoimmune blistering disease. Classic symptoms include blisters overlying urticarial plaques on the torso and extremities. The condition can result in intense pruritus that begins during the prodromal period. Excoriation disorder is related to obsessive compulsive disorder (OCD) and is characterized by recurrent skin picking that results in lesions, repeated attempts to stop or decrease the picking, and resultant mental distress or impairment in functioning. We present a case of a 59-year-old Caucasian female who presented with diffuse rash on most of her body. This particular case is notable for its concurrent severe dermatological and psychiatric components

A Case of Diabulimia in a 23-Year-Old Woman with Extensive Comorbidities

Diabulimia is defined as intentionally withholding insulin injections for the purpose of weight loss in the setting of type 1 diabetes mellitus (T1D). It is characterized as an eating disorder (ED), although it does not yet have DSM diagnosis status. Recognition of the condition among medical professionals is limited but growing

The influence of socio-demographic, psychological and knowledge-related variables alongside perceived cooking and food skills abilities in the prediction of diet quality in adults: a nationally representative cross-sectional study

Background: Interventions to increase cooking skills (CS) and food skills (FS) as a route to improving overall diet are popular within public health. This study tested a comprehensive model of diet quality by assessing the influence of socio-demographic, knowledge- and psychological-related variables alongside perceived CS and FS abilities. The correspondence of two measures of diet quality further validated the Eating Choices Index (ECI) for use in quantitative research.Methods: A cross-sectional survey was conducted in a quota-controlled nationally representative sample of 1049 adults aged 20–60 years drawn from the Island of Ireland. Surveys were administered in participants’ homes via computer-assisted personal interviewing (CAPI) assessing a range of socio-demographic, knowledge- and psychological-related variables alongside perceived CS and FS abilities. Regression models were used to model factors influencing diet quality. Correspondence between 2 measures of diet quality was assessed using chi-square and Pearson correlations.Results: ECI score was significantly negatively correlated with DINE Fat intake (r = -0.24, p < 0.001), and ECI score was significantly positively correlated with DINE Fibre intake (r = 0.38, p < 0.001), demonstrating a high agreement. Findings indicated that males, younger respondents and those with no/few educational qualifications scored significantly lower on both CS and FS abilities. The relative influence of socio-demographic, knowledge, psychological variables and CS and FS abilities on dietary outcomes varied, with regression models explaining 10–20 % of diet quality variance. CS ability exerted the strongest relationship with saturated fat intake (β = -0.296, p < 0.001) and was a significant predictor of fibre intake (β = -0.113, p < 0.05), although not for healthy food choices (ECI) (β = 0.04, p > 0.05).Conclusion: Greater CS and FS abilities may not lead directly to healthier dietary choices given the myriad of other factors implicated; however, CS appear to have differential influences on aspects of the diet, most notably in relation to lowering saturated fat intake. Findings suggest that CS and FS should not be singular targets of interventions designed to improve diet; but targeting specific sub-groups of the population e.g. males, younger adults, those with limited education might be more fruitful. A greater understanding of the interaction of factors influencing cooking and food practices within the home is needed

Wnt16 Elicits a Protective Effect Against Fractures and Supports Bone Repair in Zebrafish

Bone homeostasis is a dynamic, multicellular process which is required throughout life to maintain bone integrity, prevent fracture and respond to skeletal damage. WNT16 has been linked to bone fragility and osteoporosis in human genome wide association studies, as well as the functional haematopoiesis of leukocytes in vivo. However, the mechanisms by which WNT16 promotes bone health and repair are not fully understood. We used CRISPR-Cas9 to generate mutant zebrafish lacking Wnt16 (wnt16-/-) to study its effect on bone dynamically. wnt16 mutants displayed variable tissue mineral density and were susceptible to spontaneous fractures and the accumulation of bone calluses at an early age. Fractures were induced in the lepidotrichia of the caudal fins of wnt16-/- and wild type (WT) zebrafish; this model was used to probe the mechanisms by which Wnt16 regulates skeletal and immune cell-dynamics in vivo. In WT fins, wnt16 expression increased significantly during the early stages for bone repair. Mineralization of bone during fracture repair was significantly delayed in wnt16 mutants compared to WT zebrafish. Surprisingly, we found no evidence that the recruitment of innate immune cells to fractures or soft callus formation was altered in wnt16 mutants. However, osteoblast recruitment was significantly delayed in wnt16 mutants post-fracture, coinciding with precocious activation of the canonical Wnt signalling pathway. In situ hybridization suggests that canonical Wnt-responsive cells within fractures are osteoblast progenitors, and that osteoblast differentiation during bone repair is coordinated by the dynamic expression of runx2a and wnt16. This study highlights zebrafish as an emerging model for functionally validating osteoporosis-associated genes and investigating fracture repair dynamically in vivo. Using this model, we demonstrate that Wnt16 protects against fracture and supports bone repair, likely by modulating canonical Wnt activity, via runx2a, to facilitate osteoblast differentiation and bone matrix deposition

Living less safely through the pandemic in England for people with serious mental and physical health conditions: qualitative interviews with service users and carers of Black African, Caribbean, and South-Asian descent

Background: COVID-19 Ethnic Inequalities in Mental health and Multimorbidities (COVEIMM) is a mixed methods study to explore whether COVID-19 exacerbated ethnic health inequalities in adults with serious mental and physical health conditions. We analysed data from electronic health records for England and conducted interviews in Birmingham and Solihull, Manchester, and South London. Sites were selected because they were pilot sites for the Patient and Carer Race Equality Framework being introduced by NHS England to tackle race inequalities in mental health. Prior to the pandemic people in England with severe mental illnesses (SMIs) faced an 11–17-year reduction in life expectancy, mostly due to preventable, long-term, physical health conditions. During the pandemic there was a marked increase in deaths of those living with an SMI. Aims: This qualitative interview study aimed to understand the reasons underlying ethnic inequalities in mortality and service use during the COVID-19 pandemic for adult service users and carers of Black African, Black Caribbean, Indian, Pakistani, and Bangladeshi backgrounds living with serious multiple long-term mental and physical health conditions. Methods: We took a participatory action research approach and qualitative interviews undertaken by experts-by-experience and university researchers Participants were purposively sampled by ethnicity, diagnoses, and comorbidities across three geographically distinct sites in England. Transcriptions were coded inductively and deductively and analysed thematically. Results: Findings indicated multiple points along primary and secondary health pathways for mental and physical health that have the potential to exacerbate the unjust gap in mortality that exists for Black and Asian people with SMIs. Issues such as timely access to care (face-to-face and remote), being treated in a culturally appropriate manner with empathy, dignity and respect, and being able to use services without experiencing undue force, racism or other forms of intersectional discrimination were important themes arising from interviews. Conclusion: These poor experiences create systemic and enduring healthcare harms for racialised groups with SMIs that need to be addressed. Our findings suggest a need to address these, not only in mental health providers, but across the whole health and care system and a need to ensure more equitable healthcare partnerships with service users, carers, and communities from racialised backgrounds who are often excluded.</p

Cellular interference in craniofrontonasal syndrome: Males mosaic for mutations in the x-linked EFNB1 gene are more severely affected than true hemizygotes

Craniofrontonasal syndrome (CFNS), an X-linked disorder caused by loss-of-function mutations of EFNB1, exhibits a paradoxical sex reversal in phenotypic severity: females characteristically have frontonasal dysplasia, craniosynostosis and additional minor malformations, but males are usually more mildly affected with hypertelorism as the only feature. X-inactivation is proposed to explain the more severe outcome in heterozygous females, as this leads to functional mosaicism for cells with differing expression of EPHRIN-B1, generating abnormal tissue boundariesa process that cannot occur in hemizygous males. Apparently challenging this model, males occasionally present with a more severe female-like CFNS phenotype. We hypothesized that such individuals might be mosaic for EFNB1 mutations and investigated this possibility in multiple tissue samples from six sporadically presenting males. Using denaturing high performance liquid chromatography, massively parallel sequencing and multiplex-ligation-dependent probe amplification (MLPA) to increase sensitivity above standard dideoxy sequencing, we identified mosaic mutations of EFNB1 in all cases, comprising three missense changes, two gene deletions and a novel point mutation within the 5 untranslated region (UTR). Quantification by Pyrosequencing and MLPA demonstrated levels of mutant cells between 15 and 69. The 5 UTR variant mutates the stop codon of a small upstream open reading frame that, using a dual-luciferase reporter construct, was demonstrated to exacerbate interference with translation of the wild-type protein. These results demonstrate a more severe outcome in mosaic than in constitutionally deficient males in an X-linked dominant disorder and provide further support for the cellular interference mechanism, normally related to X-inactivation in females. © The Author 2013. Published by Oxford University Press. All rights reserved

Exploring the Connection Between Diabetes Distress and Diabulimia

Diabulimia is a disordered eating behavior that involves an individual with type 1 DM withholding insulin injection to lose weight. Diabetes distress, a term used to describe the psychological stress associated with managing diabetes, is believed to be the cause of this condition. This review aims to assess whether individuals with diabulimia have measurable evidence of diabetes distress. Studies that described patients qualitative experiences with Diabulimia were matched and compared to the criteria in the Diabetes Distress Scale. Over 40 of the 185 individuals across twelve studies were found to meet one or more criteria from the Diabetes Distress Scale. Participants were made up of 164 females, 20 males, and 1 non-reported gender. Further research is warranted to explore the prevalence of diabetes distress among patients with diabulimia

Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability

Human ZIC1 (zinc finger protein of cerebellum 1), one of five homologs of the Drosophila pair-rule gene odd-paired, encodes a transcription factor previously implicated in vertebrate brain development. Heterozygous deletions of ZIC1 and its nearby paralog ZIC4 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum, and loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects. We describe individuals from five families with heterozygous mutations located in the final (third) exon of ZIC1 (encoding four nonsense and one missense change) who have a distinct phenotype in which severe craniosynostosis, specifically involving the coronal sutures, and variable learning disability are the most characteristic features. The location of the nonsense mutations predicts escape of mutant ZIC1 transcripts from nonsense-mediated decay, which was confirmed in a cell line from an affected individual. Both nonsense and missense mutations are associated with altered and/or enhanced expression of a target gene, engrailed-2, in a Xenopus embryo assay. Analysis of mouse embryos revealed a localized domain of Zic1 expression at embryonic days 11.5-12.5 in a region overlapping the supraorbital regulatory center, which patterns the coronal suture. We conclude that the human mutations uncover a previously unsuspected role for Zic1 in early cranial suture development, potentially by regulating engrailed 1, which was previously shown to be critical for positioning of the murine coronal suture. The diagnosis of a ZIC1 mutation has significant implications for prognosis and we recommend genetic testing when common causes of coronal synostosis have been excluded