Biogeographical distribution of house dust mites: database from the literature

There has been a multitude of research into mite fauna with focus on the medical and economic implications of these species, but there is not a recent comprehensive report of all indoor house dust mite fauna worldwide. 347 articles from 1950 to the beginning of 2017 were collected through online searches using Web of Science, Google Scholar, EThOs, ProQuest Dissertations & Theses Global, Summon2.0, Interlibrary loans, and archives in the University of Reading collection, as well as the resources available at the University College of London library. Only mites which were collected from a location where people were living (i.e. sleeping and eating on a regular basis), as well as clothing, were included. Mites identified from other indoor locations, from human sputum after ingestion, or following an allergic reaction or anaphylactic shock were excluded. Specimens which were morphologically identified, as opposed to DNA identified, were incorporated. 531 species were collected from 63 countries worldwide, with the most diverse mite fauna in India (153 species), Japan (112 species), and Brazil (99 species). Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei were the three most common species, collected from 298, 235 and 155 publications respectively. There were some issues with creating this database, including the large discrepancy in the number of studies conducted within one region or country. Therefore the minimal number of studies may not be an accurate representation of all mite fauna in that country. There are many geographical and housing differences between regions within a country, as well as sampling variations. There may also be an issue with species misidentification, particularly pertinent with older publications before more accurate keys had been produced. Some publications also only searched for specific species, so many others may be excluded. Finally, there is a bias towards English-written publications. Research published in certain journals or different languages may have not been encompassed within the online searches. Some information or articles may also be overlooked due to poor translation, as often an English abstract or summary is provided but not the reminder of the publication. Therefore, although this database contains as many publications as possible, some mite fauna may still be missing. However, as this house dust mite fauna database notes specific locations and collection times, it assists with detecting the previously outlined issues of sampling bias and differences between locations

House dust mites and their genetic systems

Despite their medical implications and widespread distribution, there is limited knowledge of house dust mites. I assessed their biogeographical distribution, examined the genetic system of one of the most common species of house dust mite, Dermatophagoides farinae, and modelled different mating systems of mites, with the aim of improving understanding. This included assembling a database of house dust mite diversity, and identifying the most successful protocols for molecular work, which will save researchers time and provide a solid base for future studies. The creation of a house dust mite fauna database through published resources provided a worldwide distribution of all mites collected from homes. This may prove useful in future, particularly by allergists who are focusing on eradicating these mites for the benefit of human health. In addition, this identified the possibility of a latitudinal diversity gradient in house dust mites. Assessing D. farinae mitochondrial and nuclear genome regions through PCR and sequencing has illustrated dissimilarity between populations. This suggested that D. farinae may have been previously misidentified and the examined populations actually represent more than one species. This gives a basis for further analysis with an increased number of populations from a variety of locations. Finally, modelling and comparing different mating systems which may be found in mites, illustrate that despite the benefits of being haplodiploid, it is difficult to transition to this system from diploidy. This indicates that cytoplasmically inherited maternally-transmitted haplodiploidy is not favoured in diploid populations, forming part of the reason why many species are still in the ancestral diploid state

Staff experience of a new approach to family safeguarding in Oxfordshire Children's Social Care Services

This paper presents the findings from a qualitative study that sought to understand the experiences of frontline staff working in Oxfordshire County Council (OCC) Children's Social Care Services and their views on a new family safeguarding model (Family Solutions Plus). Focus group interviews were conducted with 20 frontline staff and managers in different teams across OCC Children's Social Care Services using video conferencing software. Thematic analysis identified three overarching themes: Preparation for the implementation of Family Solutions Plus, staff views on the implemented model, and challenges to its implementation. Staff voiced strong support for the new model, which places a much greater emphasis than previous practice on supporting the whole family, developing parenting skills and keeping children safe with their families. The challenges associated with the transition to a new model were considerable in the short term, partly due to the COVID-19 pandemic, but there was optimism that the new model could be sustained and stabilized over time

The impact of a new approach to family safeguarding in social care: initial findings from an analysis of routine data

Child safeguarding services intervene when a child is at risk of serious emotional or physical harm. Oxfordshire County Council is implementing a new approach to child safeguarding (Family Solutions Plus [FSP]) with a greater focus on whole family support and reducing the need for foster care. We sampled two cohorts of children closed within 1 year and examined the time spent in services. The sample included 474 children entering services before the new model's implementation and 561 children after. A greater proportion of children receiving FSP required a single care plan before their case was closed (85.9%; 69.4%, p < 0.001) and only experienced the lowest level plan (74.5%; 61.8%, p < 0.001). On average, this group spent less time in services for the period being observed (MD = 17.58, 95% confidence interval = 6.19, 28.96). At this early stage, no significant reduction in the number of children requiring foster care was seen (5.5%; 3.9%, p = 0.23). These initial findings suggest a potential association of FSP with a reduced number and level of care plans as well as length of time. Local authorities in England may investigate further whether FSP is a potentially useful model in improving safeguarding services

Capability engineering -an analysis of perspectives

The terms "capability" and "capability engineering" are now widely used across industry and in government procurement, but it is clear that different communities use the terms with similar, but distinctly different meanings. Using a soft systems methodological approach, an INCOSE UK working group has identified eight perspectives of capability, which have been related to Ring"s value cycle and the Hitchins" five layer model of systems engineering. It is asserted that capability is the ability to do something and that capability engineering is the overarching approach that links value, purpose, and solution of a systems problem. It is equivalent to layers 1-4 of Hitchins" Five Layer Model and is equivalent to an holistic perspective of systems engineering. There are significant practice and examples of capability engineering from (at least) the UK rail provision, defence, and Information Services and it is the view of the working group that further INCOSE guidance may be needed to ensure engineers are properly equipped to deal with capability and capability engineering.©2011 by Michael Henshaw, Duncan Kemp, Peter Lister, Andrew Daw, Alan Harding, Andrew Farncombe, Malcolm Touchin. Published and used by INCOSE with permission

Incidental findings from cancer next generation sequencing panels

Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing. Inclusion criteria included: 1) multiple pathogenic variants in the same patient; 2) pathogenic variants at a low allele fraction; and/or 3) the presence of pathogenic variants not consistent with family history. Secondary tissue analysis, complete blood count (CBC) and medical record review were conducted to further delineate the etiology of the pathogenic variants. Of 6060 NGS-MGP tests, 24 cases fulfilling our inclusion criteria were identified. Pathogenic variants were detected in TP53, ATM, CHEK2, BRCA1 and APC. 18/24 (75.0%) patients were classified as CH, 3/24 (12.5%) as mosaic, 2/24 (8.3%) related to a hematologic malignancy, and 1/24 (4.2%) as true germline. We describe a case-specific workflow to identify and interpret the nature of incidental findings on NGS-MGP. This workflow will provide oncology and genetic clinics a practical guide for the management and counselling of patients with unexpected NGS-MGP findings

Understanding the Impact of a New Approach to the Safeguarding of Children at Risk: An Evaluation Protocol

Introduction: Child Safeguarding Services intervene in situations where a child is at risk of serious emotional or physical harm. The response will vary according to the level of risk, but in serious cases, a child may need to be removed from danger and cared for by foster parents either temporarily or permanently. The number of children being taken into care has increased markedly in recent years in the United Kingdom. Oxfordshire County Council (OCC) is implementing a new approach to the welfare of children (Family Solutions Plus; FSP) in which the focus is to support the whole family and ideally reduce the need for foster care. In this paper, we describe a proposed programme of evaluation to examine the impact of FSP on the time children are in contact with services, the nature of the support provided, experience of children and families, the experience of staff, and longer term outcomes for children, particularly whether they remain within the family or need to be cared for outside the home. Methods and analysis: A mixed methods approach will be taken in an observational retrospective study of children’s social care services. Quantitative research will include descriptive analysis on data routinely collected by OCC, examining the effect on time spent in services, outcomes for children and how these outcomes are mediated by family characteristics and circumstances. Qualitative research will be carried out using individual interviews and focus groups with children, families and staff in the teams providing family safeguarding services to capture their experiences with the new model. Ethics and dissemination: This project has been registered with the OCC as a service evaluation. The qualitative studies will seek ethical approval from Oxford University Ethics Committee. A local data sharing agreement will govern the transfer of quantitative data. Results will be disseminated through newsletters, community forums, professional publications and conference presentations to national and international audiences

Characterization of 3D PET systems for accurate quantification of myocardial blood flow

Three-dimensional (3D) mode imaging is the current standard for positron emission tomography-computed tomography (PET-CT) systems. Dynamic imaging for quantification of myocardial blood flow (MBF) with short-lived tracers, such as Rb-82- chloride (Rb-82), requires accuracy to be maintained over a wide range of isotope activities and scanner count-rates. We propose new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. Methods: 1100-3000 MBq of Rb-82 or N-13-ammonia was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was performed over 5 half-lives on 9 different 3D PET-CT systems and 1 3D/twodimensional (2D) PET-only system. Dynamic images (28x15s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with <10% bias, from which corresponding dead-time, count-rates and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-tomyocardium activity ratio. Image quality was assessed via the coefficient of variation measuring non-uniformity of the left ventricle (LV) myocardium activity distribution. Results: Maximum recommended injected activity/body-weight, peak dead-time correction factor, count-rates and residual scatter bias for accurate cardiac MBF imaging were: 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence count-rates, and 2-10% on the investigated scanners. Non-uniformity of the myocardial activity distribution varied from 3-16%. Conclusion: Accurate dynamic imaging is possible on the 10 3D-PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit

The Dopamine Allosteric Agent, PAOPA, Demonstrates Therapeutic Potential in the Phencyclidine NMDA Pre-clinical Rat Model of Schizophrenia

PAOPA, a potent analog of prolyl-leucyl-glycinamide, has shown therapeutic potential at the preclinical stage for dopaminergic related illnesses, including animal models of schizophrenia, Parkinson’s disease and haloperidol-induced extrapyramidal movement disorders. PAOPA’s unique allosteric mechanism and dopamine D2 receptor specificity provide a unique composition of properties for the development of potential therapeutics for neuropsychiatric illnesses. We sought to investigate PAOPA’s therapeutic prospects across the spectrum of schizophrenia-like symptoms represented in the established phencyclidine-induced rat model of schizophrenia, (5 mg/kg PCP twice daily for 7 days, followed by 7 days of drug withdrawal). PAOPA was assessed for its effect on brain metabolic activity and across a battery of behavioral tests including, hyperlocomotion, social withdrawal, sensorimotor gating, and novel object recognition. PAOPA showed therapeutic efficacy in behavioral paradigms representing the negative (social withdrawal) and cognitive-like (novel object recognition) symptoms of schizophrenia. Interestingly, some behavioral indices associated with the positive symptoms of schizophrenia that were ameliorated in PAOPA’s prior examination in the amphetamine-sensitized model of schizophrenia were not ameliorated in the PCP model; suggesting that the deficits induced by amphetamine and PCP—while phenotypically similar—are mechanistically different and that PAOPA’s effects are restricted to certain mechanisms and systems. These studies provide insight on the potential use of PAOPA for the safe and effective treatment of schizophrenia