Species-wide distribution of highly polymorphic minisatellite markers suggests past and present genetic exchanges among house mouse subspecies

Global analysis of four minisatellite loci in House Mouse reveals unexpected long-range gene flow between populations and subspecies

Unmet need, epistemic injustice and early death: how social policy for Autistic adults in England and Wales fails to slay Beveridge's Five Giants

Around 2% of people are Autistic, but to date the impact of being Autistic on social policy receipt has not yet been considered. We, a group of Autistic academics, consider epistemic injustice, where Autistic input is excluded from the policy making process, to be a core part of Autistic disablement. We consider the impact of this using a modern iteration of Beveridge’s Five Giants: health (disease), education (ignorance), employment (idleness), poverty (want), and housing (squalor). Starting with lack of access to diagnosis and healthcare for co-occurring conditions, we identify policies that fail to account for known Autistic needs in each policy area. These failures have a cumulative impact throughout the life course; lack of accommodations within education leads to less likelihood of securing accessible employment, and greater reliance on government financial support and housing assistance. Furthermore, this impact will be increased for Autistic people who are multiply marginalised due to intersectionality. We propose changes to the policy-making process to ensure that it reflects Autistic needs and realities, allowing for the emancipation of Autistic people. We theorise that if this were to happen, the Autistic suicide rate, which is nine times that of non-Autistic people, would decline

Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

Adapting the 3D-printed Openflexure microscope enables computational super-resolution imaging

We report on a 3D printed microscope, based on a design by the Openflexure project, that uses low cost components to perform fluorescence imaging. The system is sufficiently sensitive and mechanically stable to allow the use of the SuperResolution Radial Fluctuations algorithm to obtain images with resolution better than the diffraction limit. Due to the low-cost components, the entire system can be built for approximately $1200

Development of a framework for the co-production and prototyping of public health interventions

BACKGROUND: Existing guidance for developing public health interventions does not provide information for researchers about how to work with intervention providers to co-produce and prototype the content and delivery of new interventions prior to evaluation. The ASSIST + Frank study aimed to adapt an existing effective peer-led smoking prevention intervention (ASSIST), integrating new content from the UK drug education resource Talk to Frank ( www.talktofrank.com ) to co-produce two new school-based peer-led drug prevention interventions. A three-stage framework was tested to adapt and develop intervention content and delivery methods in collaboration with key stakeholders to facilitate implementation. METHODS: The three stages of the framework were: 1) Evidence review and stakeholder consultation; 2) Co-production; 3) Prototyping. During stage 1, six focus groups, 12 consultations, five interviews, and nine observations of intervention delivery were conducted with key stakeholders (e.g. Public Health Wales [PHW] ASSIST delivery team, teachers, school students, health professionals). During stage 2, an intervention development group consisting of members of the research team and the PHW ASSIST delivery team was established to adapt existing, and co-produce new, intervention activities. In stage 3, intervention training and content were iteratively prototyped using process data on fidelity and acceptability to key stakeholders. Stages 2 and 3 took the form of an action-research process involving a series of face-to-face meetings, email exchanges, observations, and training sessions. RESULTS: Utilising the three-stage framework, we co-produced and tested intervention content and delivery methods for the two interventions over a period of 18 months involving external partners. New and adapted intervention activities, as well as refinements in content, the format of delivery, timing and sequencing of activities, and training manuals resulted from this process. The involvement of intervention delivery staff, participants and teachers shaped the content and format of the interventions, as well as supporting rapid prototyping in context at the final stage. CONCLUSIONS: This three-stage framework extends current guidance on intervention development by providing step-by-step instructions for co-producing and prototyping an intervention's content and delivery processes prior to piloting and formal evaluation. This framework enhances existing guidance and could be transferred to co-produce and prototype other public health interventions. TRIAL REGISTRATION: ISRCTN14415936 , registered retrospectively on 05 November 2014

QoE Testbed Infrastructure and Services: Enriching the End User’s Experience

Quality of Experience (QoE) is the subjective judgment of the satisfaction an end user perceives from an application running over a given network topology and configuration. The information provided by end users regarding their QoE preferences, experience and feedback is invaluable in providing a service that meets with their mobile activity needs within various access networks. The PERIMETER project progresses the QoE thematic research area by taking end user-related QoE factors for end user-centric mobility experimentation, thus empowering them to always have a service in which their QoE is high. This paper will detail the components of the PERIMETER framework and the user centric scenario based process adopted to implement and develop such a framework. This paper provides an insight into the federated testbed infrastructure, testing methodology and tools, operating system and applications used in the project, thus demonstrating PERIMETER’s innovative advances within the QoE end user domain

Sonic bombardment, noise hypersensitivity and ethics: A response to Fodstad and colleagues: ‘Assessment and treatment of noise hypersensitivity in a teenager with autism Spectrum Disorder’.

This commentary – provided by a group of Autistic researchers – reflects on a case study trialling a ‘modified Cognitive Behavioural Therapy intervention’ to address the ‘noise hypersensitivity’ and associated behaviours of an Autistic teenager, ‘Aaron’. We identify serious flaws in the evidence base behind the ‘therapy’: including failing to account for divergent Autistic sensory reactivity, aiming to remove ‘stimming’ behaviours and promoting masking. We challenge the lack of informed consent reported as given by either Aaron or a proxy and the absence of any reported ethical approval for this case study. We also strongly condemn the methods of sonic bombardment delivered upon Aaron under the guise of ‘therapy’. We conclude with three questions around the processes that led to the original article’s publication

Barriers and facilitators to use of digital health tools by healthcare practitioners and their patients, before and during the COVID-19 pandemic: a multimethods study

Objectives: To explore how healthcare practitioners (HCPs) made decisions about the implementation of digital health technologies (DHTs) in their clinical practice before and during the COVID-19 pandemic. Design: A multimethods study, comprising semistructured interviews conducted prior to the COVID-19 pandemic, supplemented with an online survey that was conducted during the pandemic with a different sample, to ensure the qualitative findings remained relevant within the rapidly changing healthcare context. Participants were recruited through HCP networks, snowballing and social media. Data were analysed thematically. Setting: Phone interviews and online survey. Participants: HCPs represented a range of professions from primary and secondary care across England, with varied socioeconomic deprivation. Results: 24 HCPs were interviewed, and 16 HCPs responded to the survey. In the interviews, HCPs described three levels where decisions were made, which determined who would have access to what DHTs: health organisation, HCP and patient levels. These decisions resulted in the unequal implementation of DHTs across health services, created barriers for HCPs using DHTs in their practice and influenced HCPs’ decisions on which patients to supply DHTs with. In the survey, HCPs described being provided support to overcome some of the barriers at the organisation and HCP level during the pandemic. However, they cited similar concerns to pre-pandemic about barriers patients faced using DHTs (eg, digital literacy). In the absence of centralised guidance on how to manage these barriers, health services made their own decisions about how to adapt their services for those who struggled with DHTs. Conclusions: Decision-making at the health organisation, HCP and patient levels influences inequalities in access to DHTs for HCPs and patients. The mobilisation of centralised information and resources during the pandemic can be viewed as good practice for reducing barriers to use of DHTs for HCPs. However, attention must also be paid to reducing barriers to accessing DHTs for patients

Public attitudes towards the use of novel technologies in their future healthcare: a UK survey

Background: Innovation in healthcare technologies can result in more convenient and effective treatment that is less costly, but a persistent challenge to widespread adoption in health and social care is end user acceptability. The purpose of this study was to capture UK public opinions and attitudes to novel healthcare technologies (NHTs), and to better understand the factors that contribute to acceptance and future use. Methods: An online survey was distributed to the UK public between April and May 2020. Respondents received brief information about four novel healthcare technologies (NHTs) in development: a laser-based tool for early diagnosis of osteoarthritis, a virtual reality tool to support diabetes self-management, a non-invasive continuous glucose monitor using microwave signals, a mobile app for patient reported monitoring of rheumatoid arthritis. They were queried on their general familiarity and attitudes to technology, and their willingness to accept each NHT in their future care. Responses were analysed using summary statistics and content analysis. Results: Knowledge about NHTs was diverse, with respondents being more aware about the health applications of mobile apps (66%), followed by laser-based technology (63.8%), microwave signalling (28%), and virtual reality (18.3%). Increasing age and the presence of a self-reported medical condition favoured acceptability for some NHTs, whereas self-reported understanding of how the NHT works resulted in elevated acceptance scores across all NHTs presented. Common contributors to hesitancy were safety and risks from use. Respondents wanted more information and evidence to help inform their decisions, ideally provided verbally by a general practitioner or health professional. Other concerns, such as privacy, were NHT-specific but equally important in decision-making. Conclusions: Early insight into the knowledge and preconceptions of the public about NHTs in development can assist their design and prospectively mitigate obstacles to acceptance and adoption