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

Astro2020 Science White Paper: Triggered High-Priority Observations of Dynamic Solar System Phenomena

Unexpected dynamic phenomena have surprised solar system observers in the past and have led to important discoveries about solar system workings. Observations at the initial stages of these events provide crucial information on the physical processes at work. We advocate for long-term/permanent programs on ground-based and space-based telescopes of all sizes - including Extremely Large Telescopes (ELTs) - to conduct observations of high-priority dynamic phenomena, based on a predefined set of triggering conditions. These programs will ensure that the best initial dataset of the triggering event are taken; separate additional observing programs will be required to study the temporal evolution of these phenomena. While not a comprehensive list, the following are notional examples of phenomena that are rare, that cannot be anticipated, and that provide high-impact advances to our understandings of planetary processes. Examples include: new cryovolcanic eruptions or plumes on ocean worlds; impacts on Jupiter, Saturn, Uranus, or Neptune; extreme eruptions on Io; convective superstorms on Saturn, Uranus, or Neptune; collisions within the asteroid belt or other small-body populations; discovery of an interstellar object passing through our solar system (e.g. 'Oumuamua); and responses of planetary atmospheres to major solar flares or coronal mass ejections.Comment: Astro2020 white pape

A reassuring presence: An evaluation of Bradford District Hospice at Home service

Within the United Kingdom, a developing role for primary care services in cancer and palliative care has resulted in an increase in palliative home care teams. The provision of professional care in the home setting seeks to provide necessary services and enhanced choice for patients whose preference is to die at home. A mismatch between patient preference for home death and the actual number of people who died at home was identified within Bradford, the locality of this study. In response to this mismatch, and reflecting the policy environment of wishing to enhance community service provision, the four Primary Care Trusts (PCTs) in the city sought to offer support to patients who wished to remain in their own homes through the final stages of a terminal illness. To offer this support they set up a dedicated hospice at home team. This would provide services and support for patients in achieving a dignified, symptom free and peaceful death, allowing families to maximise time spent together. The aim of the study was to evaluate the Bradford hospice at home service from the perspective of carers, nurses and General Practitioners. Postal questionnaires were sent to carers (n = 289), district nurses (n = 508) and GP's (n = 444) using Bradford's hospice at home service. Resulting quantitative data was analysed using the Statical Package for Social Sciences (SPSS) and qualitative data was analysed using grounded theory techniques. The data from carers, district nurses and GPs provide general support for the Bradford hospice at home service. Carers valued highly the opportunity to 'fulfil a promise' to the individual who wished to be cared for at home. District nurses and GPs cited the positive impact of access to specialist expertise. This was a 'reassuring presence' for primary healthcare teams and offered 'relief of carer anxiety' by providing prompt, accessible and sensitive care. Carers and health professionals welcomed the increased possibility of patients being cared for at home. The study identified the need to focus on improving skill levels of staff and on ensuring continuity of care

Success-First Decision Theories

The standard formulation of Newcomb's problem compares evidential and causal conceptions of expected utility, with those maximizing evidential expected utility tending to end up far richer. Thus, in a world in which agents face Newcomb problems, the evidential decision theorist might ask the causal decision theorist: "if you're so smart, why ain’cha rich?” Ultimately, however, the expected riches of evidential decision theorists in Newcomb problems do not vindicate their theory, because their success does not generalize. Consider a theory that allows the agents who employ it to end up rich in worlds containing Newcomb problems and continues to outperform in other cases. This type of theory, which I call a “success-first” decision theory, is motivated by the desire to draw a tighter connection between rationality and success, rather than to support any particular account of expected utility. The primary aim of this paper is to provide a comprehensive justification of success-first decision theories as accounts of rational decision. I locate this justification in an experimental approach to decision theory supported by the aims of methodological naturalism

Quality of life in South African Black women with alopecia: A pilot study

BACKGROUND: Alopecia has been shown to have a significant impact on quality of life (QoL), particularly in women. However, there are no data for African populations. This study was conducted to pilot an original questionnaire and a model-based methodology to measure QoL and its determinants in a sample of South African Black women of African ancestry with alopecia. METHODS: Fifty participants aged 21-79 years were randomly chosen from patients presenting to dermatologists with alopecia. We used an original questionnaire consisting of 24 items grouped into those assessing the respective impacts of subjective symptoms, objective signs, and relationship issues, measured on a four-level scale. These were then combined using component-based structural equation modeling to return a QoL index (QLI) and to rank the factors contributing to this. RESULTS: On a scale ranging from 0 (high QoL) to 100 (severely decreased QoL), we found a mean QLI of 67.7. The negative impact of alopecia on QoL was higher in younger patients than older patients. The factors with the highest impact were those relating to the subjective experience of alopecia and self-image (56.3%), followed by those relevant to relationships and interaction with other people (34.8%). The presence of objective symptoms and signs such as pruritus was of minor importance (8.9%). CONCLUSIONS: Although not a life-threatening condition, alopecia may seriously impair QoL, particularly by inducing anxiety and reducing self-esteem among African women. Healthcare practitioners should be mindful of this and intervene appropriately to mitigate these effects

Background Light in Potential Sites for the ANTARES Undersea Neutrino Telescope

The ANTARES collaboration has performed a series of {\em in situ} measurements to study the background light for a planned undersea neutrino telescope. Such background can be caused by $^{40}$K decays or by biological activity. We report on measurements at two sites in the Mediterranean Sea at depths of 2400~m and 2700~m, respectively. Three photomultiplier tubes were used to measure single counting rates and coincidence rates for pairs of tubes at various distances. The background rate is seen to consist of three components: a constant rate due to $^{40}$K decays, a continuum rate that varies on a time scale of several hours simultaneously over distances up to at least 40~m, and random bursts a few seconds long that are only correlated in time over distances of the order of a meter. A trigger requiring coincidences between nearby photomultiplier tubes should reduce the trigger rate for a neutrino telescope to a manageable level with only a small loss in efficiency.Comment: 18 pages, 8 figures, accepted for publication in Astroparticle Physic

Constitutivism

A brief explanation and overview of constitutivism

Stability of two-class armour berm breakwaters: An experimental study

The recession of a berm breakwater is a key parameter in ensuring its stability, and functionality, to protect coastal areas against wave impacts. Consequently, consideration of the expected recession in structural design is required to ensure the required objectives of the structure. In this study, physical model laboratory experiments were conducted to measure the recession of two-class armour berm breakwaters in response to varying sea state conditions (wave height, wave period, storm duration, and water depth at the structure\u27s toe) and geometrical parameters (berm elevation from still water level, berm width, and rock size). A total of 110 tests were conducted under irregular wave forcing and the results were compared with those of existing formulae, derived specifically for mass armour and Icelandic-type berm breakwaters. Of the existing formulae, the Sigurdarson and Van der Meer (2013) formula that is derived for both mass armour and Icelandic-type berm breakwater outperforms the other formulas. Subsequently, a new empirical formula was developed to estimate the erosion depth based on the dimensionless water depth. The findings from this study could be instrumental for the structural design of two-class armour berm breakwaters under different sea states and geometrical configurations

The type and frequency of interactions that occur between staff and children outside in Early Years Foundation Stage settings during a fixed playtime period when there are tricycles available

This study reports on an investigation into adult and child interactions observed in the outdoor play environment in four Local Authority early years foundation stage settings in England. In this instance the common two features across the settings were the presence of tricycles and a timetabled outdoor play period. In total, across the four schools, there were 204 children. The study aimed to gain an understanding of the nature of the dialogues between staff and children, that is, the types of exchange that occurred when either the child approached an adult or the adult approached a child. The most frequent type of utterance was also analysed. The study concludes that adults in these settings spoke more than children and the greatest type of utterance was that of the adult about domestic matters. When the child initiated the conversation there were more extended child utterances than domestic utterances. This may suggest that children wish to be involved in conversations of depth and meaning and that staff need to become aware of how to develop this conversational language with children