Takayasu arteritis: criteria for surgical intervention should not be ignored.

Takayasu aortoarteritis is a rare, chronic granulomatous panarteritis with significant morbidity amongst young patients. Current challenges include a lack of awareness about the condition, delays in diagnosis due to its varied presentation, and suboptimal methods for assessing disease activity. The development of noninvasive imaging including magnetic resonance angiography and positron emission tomography is aiding earlier diagnosis. Early initiation of immunosuppressive treatment is crucial to control active inflammation and minimize arterial injury. Recent studies investigating biological agents such as tumour necrosis factor- α antagonists are encouraging. Surgical revascularization should only be undertaken following careful consideration, as restenosis is common. The indications for considering intervention include uncontrolled hypertension due to renal artery stenosis, severe symptomatic coronary artery or cerebrovascular disease, severe aortic regurgitation, stenotic or occlusive lesions resulting in critical limb ischemia, and aneurysms at risk of rupture. In these cases, the risk benefit ratio for intervention is good. Open surgery, at present, has better outcomes compared to endovascular techniques. However, technological advances in endovascular treatment are continually improving. Controlling disease activity prior to and following revascularization is key to preventing complications. A multidisciplinary approach to the diagnosis and management of Takayasu arteritis is essential to achieve satisfactory patient outcomes

Evaluation of the English version of the Fear of COVID-19 Scale and its relationship with behavior change and political beliefs

The COVID-19 pandemic has many individuals around the world fearing for their lives. The constant news coverage, rapid transmission, and relatively high mortality rate, make fearfulness a natural response. To assess the fear of COVID-19, the Fear of COVID-19 Scale (FCV-19S) was developed. The primary aim of the present study was to conduct the first psychometric assessment and validation of the English version of the FCV-19S. Two samples were collected in New Zealand. Sample 1 comprised 1624 participants of which 1397 completed all questions and were used in the analyses. Sample 2 comprised 1111 participants of which 1023 completed all questions and were used in the analyses. Several psychometric tests were conducted to ascertain the scale’s reliability and validity. Across both samples, the FCV-19S had high internal consistency. Consistent with the earlier validation studies, the FCV-19S displayed a moderately strong relationship with the perceived infectability and germ aversion subscales of the perceived vulnerability to disease scale (PVDS). Furthermore, FCV-19S scores were negatively correlated with the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) scores. With respect to the motivating role of fear, there was a significant relationship between FCV-19S scores and adherence to the lockdown rules that were implemented in New Zealand. Finally, consistent with recent reports on the politicization of the COVID-19 pandemic, an exploratory question found that participants who rated themselves as more conservative tended to report lower FCV-19S scores. The English version of the COVID-19S is a sound unidimensional scale with robust psychometric properties and can be used with confidence among English-speaking populations

Electronic Liquid Crystal Phases of a Doped Mott Insulator

The character of the ground state of an antiferromagnetic insulator is fundamentally altered upon addition of even a small amount of charge. The added charges agglomerate along domain walls at which the spin correlations, which may or may not remain long-ranged, suffer a $\pi$ phase shift. In two dimensions, these domain walls are ``stripes'' which are either insulating, or conducting, i.e. metallic rivers with their own low energy degrees of freedom. However, quasi one-dimensional metals typically undergo a transition to an insulating ordered charge density wave (CDW) state at low temperatures. Here it is shown that such a transition is eliminated if the zero-point energy of transverse stripe fluctuations is sufficiently large in comparison to the CDW coupling between stripes. As a consequence, there exist novel, liquid-crystalline low-temperature phases -- an electron smectic, with crystalline order in one direction, but liquid-like correlations in the other, and an electron nematic with orientational order but no long-range positional order. These phases, which constitute new states of matter, can be either high temperature supeconductors or two-dimensional anisotropic ``metallic'' non-Fermi liquids. Evidence for the new phases may already have been obtained by neutron scattering experiments in the cuprate superconductor, La_{1.6-x}Nd_{0.4}Sr_xCuO_{4}.Comment: 5 pages in RevTex with two figures in ep

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Large-scale assessment of 7-11-year-olds’ cognitive and sensorimotor function within the Born in Bradford longitudinal birth cohort study [version 1; peer review: 1 approved, 1 approved with reservations]

Background: Cognitive ability and sensorimotor function are crucial aspects of children’s development, and are associated with physical and mental health outcomes and educational attainment. The current project forms part of the Born in Bradford (BiB) longitudinal birth-cohort study, and involved measuring sensorimotor and cognitive function in over 15,000 children aged 7-10 years. This paper describes the large-scale data collection process and presents initial analyses of the data, including the relationship between cognition/sensorimotor ability and age and task difficulty, and associations between tasks. Method: Data collection was completed in 86 schools between May 2016 and July 2019. Children were tested at school, individually, using a tablet computer with a digital stylus or finger touch for input. Assessments comprised a battery of three sensorimotor tasks (Tracking, Aiming, & Steering) and five cognitive tasks (three Working Memory tasks, Inhibition, and Processing Speed), which took approximately 40 minutes. Results: Performance improved with increasing age and decreasing task difficulty, for each task. Performance on all three sensorimotor tasks was correlated, as was performance on the three working memory tasks. In addition, performance on a composite working memory score correlated with performance on both inhibition and processing speed. Interestingly, within age-group variation was much larger than between age-group variation. Conclusions: The current project collected computerised measures of a range of cognitive and sensorimotor functions at 7-10 years of age in over 15,000 children. Performance varied as expected by age and task difficulty, and showed the predicted correlations between related tasks. Large within-age group variation highlights the need to consider the profile of individual children in studying cognitive and sensorimotor development. These data can be linked to the wider BiB dataset including measures of physical and mental health, biomarkers and genome-wide data, socio-demographic information, and routine data from local health and education services

ParaMED Home: A protocol for a randomised controlled trial of paramedic assessment and referral to access medical care at home

<p>Abstract</p> <p>Background</p> <p>In Australia approximately 25% of Emergency Department (ED) attendances are via ambulance. ED overcrowding in Australia, as in many countries, is common. Measures to reduce overcrowding include the provision of enhanced timely primary care in the community for appropriate low risk injury and illness. Therefore paramedic assessment and referral to a community home hospital service, in preference to transfer to ED, may confer clinical and cost benefit.</p> <p>Methods/Design</p> <p>A randomised controlled trial. Consenting adult patients that call an ambulance and are assessed by paramedics as having an eligible low risk problem will be randomised to referral to ED via ambulance transfer or referral to a rapid response service that will assess and treat the patient in their own residence. The primary outcome measure is requirement for unplanned medical attention (in or out of hospital) in the first 48 hours. Secondary outcomes will include a number of other clinical endpoints. A cost effectiveness analysis will be conducted.</p> <p>Discussion</p> <p>If this trial demonstrates clinical non-inferiority and cost savings associated with the primary assessment service, it will provide one means to safely address ED overcrowding.</p> <p>Trial Registration</p> <p>Australian and New Zealand Clinical Trials Registry Number <a href="http://www.anzctr.org.au/trial_view.aspx?ID=335818">12610001064099</a></p

Mathematical practices and mathematical modes of enquiry: Same or different?

Background: In this paper, I share a case study of a teacher’s work on mathematics tasks in the context of a ‘mathematics for teaching’ course aiming to develop mathematical content understandings and mathematical practices among primary teachers in one South African province. The course was developed in a national context of concerns about the nature and levels of primary teachers’ mathematical knowledge. Theories viewing mathematical practices as fundamental, contrasted with those that view mathematical practices and mathematical content in more separate and ‘to be integrated’ ways, are used to frame the analysis and ritically reflect on the findings. Results: Data from this teacher’s pre-test and selected course assessments and interactions suggest that while he was able to develop some aspects of the mathematical practices described in the literature, his overall orientation remained attuned to memorization and recall. Findings also pointed to an ongoing reliance on external validation of the ‘correctness’ of his answers. Conclusions: The data suggest that the presence of elements of mathematical practices cannot be viewed as equivalent to the presence of mathematical modes of enquiry. The analysis presented in this paper suggests that while elements of mathematical practices can be developed, moving towards an encompassing orientation to mathematical modes of enquiry may require more central focus on problem-solving approaches to achieve a change in orientation

Growing up in Bradford: protocol for the age 7-11 follow up of the Born in Bradford birth cohort.

BACKGROUND: Born in Bradford (BiB) is a prospective multi-ethnic pregnancy and birth cohort study that was established to examine determinants of health and development during childhood and, subsequently, adult life in a deprived multi-ethnic population in the north of England. Between 2007 and 2010, the BiB cohort recruited 12,453 women who experienced 13,776 pregnancies and 13,858 births, along with 3353 of their partners. Forty five percent of the cohort are of Pakistani origin. Now that children are at primary school, the first full follow-up of the cohort is taking place. The aims of the follow-up are to investigate the determinants of children's pre-pubertal health and development, including through understanding parents' health and wellbeing, and to obtain data on exposures in childhood that might influence future health. METHODS: We are employing a multi-method approach across three data collection arms (community-based family visits, school based physical assessment, and whole classroom cognitive, motor function and wellbeing measures) to follow-up over 9000 BiB children aged 7-11 years and their families between 2017 and 2021. We are collecting detailed parent and child questionnaires, cognitive and sensorimotor assessments, blood pressure, anthropometry and blood samples from parents and children. Dual x-ray absorptiometry body scans, accelerometry and urine samples are collected on subsamples. Informed consent is collected for continued routine data linkage to health, social care and education records. A range of engagement activities are being used to raise the profile of BiB and to disseminate findings. DISCUSSION: Our multi-method approach to recruitment and assessment provides an efficient method of collecting rich data on all family members. Data collected will enhance BiB as a resource for the international research community to study the interplay between ethnicity, socioeconomic circumstances and biology in relation to cardiometabolic health, mental health, education, cognitive and sensorimotor development and wellbeing

Pneumocystis cell wall β-glucan stimulates calcium-dependent signaling of IL-8 secretion by human airway epithelial cells

<p>Abstract</p> <p>Background</p> <p>Respiratory failure secondary to alveolar inflammation during <it>Pneumocystis </it>pneumonia is a major cause of death in immunocompromised patients. Neutrophil infiltration in the lung of patients with <it>Pneumocystis </it>infection predicts severity of the infection and death. Several previous studies indicate that airway epithelial cells release the neutrophil chemoattractant proteins, MIP-2 (rodents) and IL-8 (humans), in response to <it>Pneumocystis </it>and purified <it>Pneumocystis </it>cell wall β-glucans (PCBG) through the NF-κB-dependent pathway. However, little is known about the molecular mechanisms that are involved in the activation of airway epithelium cells by PCBG resulting in the secretion of IL-8.</p> <p>Method</p> <p>To address this, we have studied the activation of different calcium-dependent mitogen-activated protein kinases (MAPKs) in 1HAEo^-cells, a human airway epithelial cell line.</p> <p>Results</p> <p>Our data provide evidence that PCBG induces phosphorylation of the MAPKs, ERK, and p38, the activation of NF-κB and the subsequently secretion of IL-8 in a calcium-dependent manner. Further, we evaluated the role of glycosphingolipids as possible receptors for β-glucans in human airway epithelial cells. Preincubation of the cells with D-<it>threo</it>-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) a potent inhibitor of the glycosphingolipids synthesis, prior to PCBG stimulation, significantly decreased IL-8 production.</p> <p>Conclusion</p> <p>These data indicate that PCBG activates calcium dependent MAPK signaling resulting in the release of IL-8 in a process that requires glycosphingolipid for optimal signaling.</p