Light Streak Photometry and Streaktools

Context. The accuracy of photometric calibration has gradually become a limiting factor in various fields of astronomy, limiting the scientific output of a host of research. Calibration using artificial light sources in low earth orbit remains largely unexplored. Aims. We aim to demonstrate that photometric calibration using light sources in low earth orbit is a viable and competitive alternative/complement to current calibration techniques, and explore the associated ideas and basic theory. Methods. We present the publicly-available Python code Streaktools as a means to simulate and perform photometric calibration using real and simulated light streaks. We use Streaktools to perform `pill' aperture photometry on 131 simulated streaks, and MCMC-based PSF model-fitting photometry on 425 simulated streaks in an attempt to recover the magnitude zeropoint of a real exposure of the DECam instrument on the Blanco 4m telescope. Results. We show that calibration using pill photometry is too inaccurate to be useful, but that PSF photometry is able to produce unbiased and accurate ($1\sigma$ error = 3.4mmag) estimates of the zeropoint of a real image in a realistic scenario, with a reasonable light source.Comment: 7 pages, 5 figures. Submitted to Astronomy & Astrophysics, 13 November 202

A study of dementia in a rural population

Dementia, in particular Alzheimer's disease, has been widely investigated in clinical settings. Moreover, many epidemiological studies have been carried out to estimate the prevalence and incidence of dementia and, less frequently, Alzheimer's disease. There have also been studies of ageing cohorts to examine mental changes associated with ageing. There has, however, been little research on unselected elderly populations which has been detailed enough to examine the relationship between normal and abnormal mental ageing. The aim of this study was to investigate the distribution of the indices of dementia in a rural population. This allowed investigation of the hypothesis that variables associated with dementia, in particular Alzheimer's disease, are distributed bimodally in the population and allowed investigation of possible associations with these distributions. It also provided prevalence estimates of dementia in a rural population. A population sample of women aged 70 to 79 was selected from a rural Cambridgeshire health centre. Using the Cambridge Examination for Mental Disorders in the Elderly all aspects required for the diagnosis of dementia and tentative differential diagnosis were collected on 365 women. There was no evidence of bimodality in any of the derived scales, whether cognitive, behavioural or ischaemic. The prevalence of dementia of all types and levels, including mild, was 4.3% in the 70 to 74 age group and 11.7% in the 75 to 79 age group. For more severe dementia a prevalence of 2.8% was found in the 75 to 79 age group, and 0% in the 70 to 74 age group. The rates for more severe dementia were lower than other recent prevalence studies in the UK, whereas the rates for all levels of severity were higher. The tentative diagnosis of Alzheimer's disease accounted for 52% of the diagnoses of dementia and multi-infarct dementia for 31%. Age, social class and education were all significantly and independently associated with scores on the longer cognitive scales (Mini-Mental State Examination and the CAMCOG scale of CAMDEX). Risk factors suggested in the literature for dementia, Alzheimer's disease and cognitive impairment was also investigated. Few factors were associated with either cognitive function or dementia. Age was the only variable associated with both cognitive function and the diagnosis of dementia. Only small proportions of the population were exposed to postulated risk factors and these risk factors, if proven, would account for little population excess risk. In this study no significant separation of performance on cognitive or behavioural scales between the demented and the non-demented was found. This could have been due to the small numbers in the tails of the frequency distributions but, if true, it is suggested that this observation might be related to the continuous distribution of underlying neuropathological lesions, such as plaques and tangles, noted in autopsy series of unselected populations. If so, current research into the mechanisms of the dementias may have implications for the understanding of cognitive decline noted in the non-demented elderly over time

Laboratory aspects of von Willebrand disease: test repertoire and options for activity assays and genetic analysis

The deficiency or abnormal function of von Willebrand factor (VWF) causes von Willebrand disease (VWD), the most frequent inherited bleeding disorder. The laboratory diagnosis of VWD can be difficult as the disease is heterogeneous and an array of assays is required to describe the phenotype. Basic classification of quantitative (type 1 and 3) and qualitative (type 2) VWD variants requires determination of VWF antigenic (VWF:Ag) levels and assaying of VWF ristocetin cofactor (VWF:RCo) activity, determining the capacity of VWF to interact with the platelet GPIb-receptor. Knowing the VWF:RCo activity is essential for identifying, subtyping and monitoring VWD, but the assay is poorly standardized and many protocols do not fulfil the clinical need in all situations. This has led to the development of novel activity assays, independent of ristocetin, with enhanced assay characteristics. Results from the first independent clinical evaluations are promising, showing that they are reliable and suitable for VWD diagnosis. The qualitative type 2 VWF deficiency can be further divided into four different subtypes (A, B, M and N) using specific assays that explore other activities or the size distribution of VWF multimers. These methods are discussed herein. However, in a number of patients it may be difficult to correctly classify the VWD phenotype and genetic analysis may provide the best option to clarify the disorder, through mutation identification

Effect of the VWF promoter (GT)n repeat and single-nucleotide polymorphism c.-2527G>A on circulating von Willebrand factor levels under normal conditions.

Thrombosis and Hemostasi

von Willebrand factor variant p.Arg924Gln marks an allele associated with reduced von Willebrand factor and factor VIII levels

Background: von Willebrand factor (VWF) variant c.2771G>A; p.R924Q has been described as a benign polymorphism or a possible marker for a null allele and been associated with mild bleeding phenotypes. It was identified in several patients in recent type 1 von Willebrand disease (VWD) studies. Objectives: To determine whether the p.R924Q allele contributes to reduced VWF levels and type 1 VWD. Methods: One thousand one hundred and fifteen healthy controls and 148 index cases from the MCMDM-1VWD study were genotyped for c.2771G>A; VWF and FVIII levels were analyzed in ABO blood group stratified individuals and the p.R924Q variant was expressed in 293 EBNA cells. Results: c.2771G>A was present in six index cases, five of whom had a second VWF variant which probably contributed to the phenotype. A common core haplotype identified in families, which included the rare G allele of c.5843-8C>G, was present in the majority of 35 c.2771G>A heterozygous controls. c.2771G>A contributed about 10% variance in VWF and FVIII levels in controls and 35% variance when co-inherited with blood group O. Recombinant p.R924Q VWF had no effect on in vitro expression and heterozygous family members had normal VWF-FVIII binding and normal clearance of VWF and FVIII. Conclusions: The allele bearing c.2771A leads to reductions in VWF and FVIII levels particularly in combination with blood group O. Its inheritance alone may be insufficient for VWD diagnosis, but it appears to be associated with a further VWF level reduction in individuals with a second VWF mutation and it contributes to population variance in VWF and FVIII levels

A feminist new materialist experiment: exploring what else gets produced through encounters with children’s news media

In this paper we are concerned to grapple with the ways in which real world issues directly impact children’s lives, and ask what else gets produced through encounters with children’s global news media specifically within the contexts of the UK and Norway. Our aim is to experiment with worldling practices as a means to open up generative possibilities to encounter and reconfigure difficult knowledges. We take two contemporary events: the 2017 Grenfell Tower fire tragedy in London, and the 2018 Marjory Stoneman high school shooting massacre in Florida, as a means to attend to ways in which affects are materialised across multiple times and spaces. News reports of these harrowing events, alongside what they produced, in terms of child activism, racism and toxic masculinity, provided a catalyst for a feminist new materialist experiment in generating other knowledges through material-affective-embodied encounters. Newspapers, glue, sticky tape, string, torches, bags and a cartridge for a firearm undertook important work within a speculative workshop, where a small number of early childhood researchers came together to be open to multiple and experimental ways of (k)not-knowing in order to formulate collectively shared problems. Following Manning (2016) we recognise that to avoid getting stuck in familiar ways of thinking and doing we need to undertake research differently. We wondered how might the re-materialisation of these events (through objects, artefacts, sounds and images) shift our thinking about childhood in other directions. We dwell upon the affective work that these high-profile news events perform, and how they might become rearticulated through affective encounters with materiality. Attending to how these events worked on us involves staying with the trouble (Haraway, 2016) as it becomes reignited, mutated and amplified across time and in different contexts. Our goal is to generate other possibilities that seek to reconfigure the ‘image of the child’. By resisting comforts of recognition, reflection and identification we reach beyond what we think we know about how children are in the world, and instead argue for their entanglement with difficult knowledges through, ours and their, world-making practices

Genetic analysis of haemophilia A in Bulgaria

BACKGROUND: Haemophilias are the most common hereditary severe disorders of blood clotting. In families afflicted with heamophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostical strategy for carriership determination and prenatal diagnostics of haemophilia A in Bulgarian haemophilic population. METHODS: A diagnostical strategy consisting of screening for most common mutations in the factor VIII gene and analysis of a panel of eight linked to the factor VIII gene locus polymorphisms was established. RESULTS: Polymorphic analysis for carrier status determination of haemophilia A was successful in 30 families out of 32 (94%). Carrier status was determined in 25 of a total of 28 women at risk (89%). Fourteen prenatal diagnoses in women at high risk of having a haemophilia A – affected child were performed, resulting in 6 healthy boys and 5 girls. CONCLUSION: The compound approach proves to be a highly informative and cost-effective strategy for prevention of recurrence of haemophilia A in Bulgaria. DNA analysis facilitates carriership determination and subsequent prenatal diagnosis in the majority of Bulgarian families affected by haemophilia A

Nitrides as ammonia synthesis catalysts and as potential nitrogen transfer reagents

In this article, an overview of the application of selected metal nitrides as ammonia synthesis catalysts is presented. The potential development of some systems into nitrogen transfer reagents is also described

Identification and characterisation of mutations associated with von Willebrand disease in a Turkish patient cohort

Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); however, these have mostly focused on European and North American populations. This study aimed to investigate mutation spectrum in 26 index cases (IC) from Turkey diagnosed with all three VWD types, the majority (73%) with parents who were knowingly related. IC were screened for mutations using multiplex ligation-dependent probe amplification and analysis of all von Willebrand factor gene (VWF) exons and exon/intron boundaries. Selected missense mutations were expressed in vitro. Candidate VWF mutations were identified in 25 of 26 IC and included propeptide missense mutations in four IC (two resulting in type 1 and two in recessive 2A), all influencing VWF expression in vitro. Four missense mutations, a nonsense mutation and a small in-frame insertion resulting in type 2A were also identified. Of 15 type 3 VWD IC, 13 were homozygous and two compound heterozygous for 14 candidate mutations predicted to result in lack of expression and two propeptide missense changes. Identification of intronic breakpoints of an exon 17–18 deletion suggested that the mutation resulted from non-homologous end joining. This study provides further insight into the pathogenesis of VWD in a population with a high degree of consanguineous partnerships

Diagnosing von Willebrand disease: genetic analysis

Investigation of a patient with possible von Willebrand disease (VWD) includes a range of phenotypic analyses. Often, this is sufficient to discern disease type, and this will suggest relevant treatment. However, for some patients, phenotypic analysis does not sufficiently explain the patient's disorder, and for this group, genetic analysis can aid diagnosis of disease type. Polymerase chain reaction and Sanger sequencing have been mainstays of genetic analysis for several years. More recently, next-generation sequencing has become available, with the advantage that several genes can be simultaneously analyzed where necessary, eg, for discrimination of possible type 2N VWD or mild hemophilia A. Additionally, several techniques can now identify deletions/duplications of an exon or more that result in VWD including multiplex ligation-dependent probe amplification and microarray analysis. Algorithms based on next-generation sequencing data can also identify missing or duplicated regions. These newer techniques enable causative von Willebrand factor defects to be identified in more patients than previously, aiding in a specific VWD diagnosis. Genetic analysis can also be helpful in the discrimination between type 2B and platelet-type VWD and in prenatal diagnosis for families with type 3