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Abstract Space weather has the potential to impact ground-based technologies on Earth, affecting many systems including railway signalling. This study uses a recently developed model to analyse the impact of geomagnetically induced currents on railway signalling systems in the United Kingdom during the March 1989 and October 2003 geomagnetic storms. The March 1989 storm is also scaled to estimate a 1-in-100 year and a 1-in-200 year extreme storm. Both the Glasgow to Edinburgh line, and the Preston to Lancaster section of the West Coast Main Line are modelled. No “right side” failures (when unoccupied sections appear occupied) are suggested to have occurred during either storm, and the total number of potential “wrong side” failures (when occupied sections appear clear) is low. However, the modelling indicates “right side” and “wrong side” failures are possible on both routes during the 1-in-100 year and 1-in-200 year extreme storms, with the Glasgow to Edinburgh line showing more total misoperations than the Preston to Lancaster section of the West Coast Main Line. A 1-in-100 year or 1-in-200 year extreme storm would result in misoperations over an extended period of time, with most occurring over a duration of 2–3 h either side of the peak of the storm.

Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and the elderly, severe disease of the lower respiratory tract (LRT) often occurs and can develop into chronic airway disease. A better understanding of how an acute RSV infection transitions to a LRT chronic inflammatory disease is critically important to improve patient care and long-term health outcomes. To model acute and chronic phases of the disease, we infected wild-type C57BL/6 and toll-like receptor 7 knockout (TLR7 KO) mice with RSV and temporally assessed nasal, airway and lung inflammation for up to 42 days post-infection. We show that TLR7 reduced viral titers in the URT during acute infection but promoted pronounced pathogenic and chronic airway inflammation and hyperreactivity in the LRT. This study defines a hitherto unappreciated molecular mechanism of lower respiratory pathogenesis to RSV, highlighting the potential of TLR7 modulation to constrain RSV pathology to the URT.

Abstract Background Increasing physical activity in older adults remains a key public health priority in countries with a high burden of non-communicable disease, yet current interventions have failed to substantially increase population uptake with UK data suggesting that only half of 65–74 year olds report meeting recommended levels. The aim of this study was to conduct a systematic and inductive qualitative synthesis of the large body of qualitative research describing what influences physical activity at this age, and older adults’ experiences of physical activity. Methods A qualitative meta-ethnography was chosen as the study design as this inductive approach can provide novel insights and generate new theory about physical activity and ageing. Papers were identified by searching electronic databases and key citations. Peer-reviewed primary qualitative studies and systematic reviews were included if they met the following inclusion criteria: community-dwelling participants aged 60 years or older or in the retirement transition period; reporting on leisure-time physical activity; utilising a rigorous qualitative methodology. A line of argument approach was employed to generate a theory about how older adults think and feel about physical activity. Results Thirty-nine papers met the inclusion criteria and were synthesised. The emergent theory suggested transition to older age can challenge people’s sense of self and their role in life. Physical activity can help in regaining feelings of purpose, of being needed in collective group activity, and by creating habitual routine and structure to the day. In overcoming real and perceived barriers, and by taking up or sustaining physical activities, older adults can further build self-esteem all of which contributes to a fulfilling older age. Conclusion Current failures to increase population levels of physical activity in older adults may be explained by an approach overly focused on the health benefits of activity. Insights from this study suggest we need to reframe our approach to consider the wider set of goals and aspirations which are of greater personal importance to older adults, and future interventions should focus on how physical activity can contribute to life satisfaction, sense of purpose, and sense of role fulfilment in older age. Trial registration Registered prospectively on PROSPERO on 29th March 2013: CRD42013003796.

Abstract Background More people are living longer lives leading to a growth in the population of older adults, many of whom have comorbidities and low levels of physical function. Physical activity in later life can prevent or delay age-related disability. Identifying a cost-effective means of increasing physical activity in older adults therefore remains an important public health priority. Physical Activity Facilitation (PAF) is an intervention shown to increase physical activity in adults with depression. The PAF model was modified for a population of older adults at risk of disability. This study aimed to assess the feasibility of undertaking a definitive RCT of the PAF intervention in the target population. Methods A pilot randomised controlled trial (RCT) was delivered through primary care. Patients at risk of disability and who were not meeting recommended levels of physical activity were recruited through postal invitation and direct approach in the practice waiting room. Those meeting eligibility criteria were enrolled and randomised at a 2:1 ratio to the PAF intervention and control. Behaviour change techniques were used by facilitators with participants over the telephone and face-to-face for 6 months. Outcome measures including physical function, physical activity, depression, social support, and quality of life were collected at baseline and at 6 months. Results A high proportion of patients responded to the initial invitation (68%), yet many were ineligible due to high levels of self-reported physical activity and baseline physical function. Fifty-one participants were recruited to the trial, with an average age of 74 years (range 65–89), and there were high rates of adherence and retention to the study (94% follow-up at 6 months). The majority of outcome data collected from participants was complete; however, the validated scale used to measure self-reported physical activity was associated with high levels of missing data. Conclusions The findings of this pilot RCT suggest that it is feasible to deliver a definitive RCT of the PAF intervention in this population. Further work is required to improve the efficiency of recruitment and to minimise missing data from self-reported physical activity measures. Trial registration Current controlled trials ISRCTN80470273. Registered 25 October 2013.

Abstract Background Dating and relationship violence (DRV)—intimate partner violence during adolescence—encompasses physical, sexual and emotional abuse. DRV is associated with a range of adverse health outcomes including injuries, sexually transmitted infections, adolescent pregnancy and mental health issues. Experiencing DRV also predicts both victimisation and perpetration of partner violence in adulthood. Prevention targeting early adolescence is important because this is when dating behaviours begin, behavioural norms become established and DRV starts to manifest. Despite high rates of DRV victimisation in England, from 22 to 48% among girls and 12 to 27% among boys ages 14–17 who report intimate relationships, no RCTs of DRV prevention programmes have taken place in the UK. Informed by two school-based interventions that have shown promising results in RCTs in the USA—Safe Dates and Shifting Boundaries—Project Respect aims to optimise and pilot a DRV prevention programme for secondary schools in England. Methods Design: optimisation and pilot cluster RCT. Trial will include a process evaluation and assess the feasibility of conducting a phase III RCT with embedded economic evaluation. Cognitive interviewing will inform survey development. Participants: optimisation involves four schools and pilot RCT involves six (four intervention, two control). All are secondary schools in England. Baseline surveys conducted with students in years 8 and 9 (ages 12–14). Follow-up surveys conducted with the same cohort, 16 months post-baseline. Optimisation sessions to inform intervention and research methods will involve consultations with stakeholders, including young people. Intervention: school staff training, including guidance on reviewing school policies and addressing ‘hotspots’ for DRV and gender-based harassment; information for parents; informing students of a help-seeking app; and a classroom curriculum for students in years 9 and 10, including a student-led campaign. Primary outcome: the primary outcome of the pilot RCT will be whether progression to a phase III RCT is justified. Testing within the pilot will also determine which of two existing scales is optimal for assessing DRV victimisation and perpetration in a phase III RCT. Discussion This will be the first RCT of an intervention to prevent DRV in the UK. If findings indicate feasibility and acceptability, we will undertake planning for a phase III RCT of effectiveness. Trial registration ISRCTN, ISRCTN 65324176. Registered 8 June 2017.

The incapability to move the facial muscles is known as facial palsy, and it affects various abilities of the patient, for example, performing facial expressions. Recently, automatic approaches aiming to diagnose facial palsy using images and machine learning algorithms have emerged, focusing on providing an objective evaluation of the paralysis severity. This research proposes an approach to analyze and assess the lesion severity as a classification problem with three levels: healthy, slight, and strong palsy. The method explores the use of regional information, meaning that only certain areas of the face are of interest. Experiments carrying on multi-class classification tasks are performed using four different classifiers to validate a set of proposed hand-crafted features. After a set of experiments using this methodology on available image databases, great results are revealed (up to 95.61% of correct detection of palsy patients and 95.58% of correct assessment of the severity level). This perspective leads us to believe that the analysis of facial paralysis is possible with partial occlusions if face detection is accomplished and facial features are obtained adequately. The results also show that our methodology is suited to operate with other databases while attaining high performance, even though the image conditions are different and the participants do not perform equivalent facial expressions.

Humans express their emotions verbally and through actions, and hence emotions play a fundamental role in facial expressions and body gestures. Facial expression recognition is a popular topic in security, healthcare, entertainment, advertisement, education, and robotics. Detecting facial expressions via gesture recognition is a complex and challenging problem, especially in persons who suffer face impairments, such as patients with facial paralysis. Facial palsy or paralysis refers to the incapacity to move the facial muscles on one or both sides of the face. This work proposes a methodology based on neural networks and handcrafted features to recognize six gestures in patients with facial palsy. The proposed facial palsy gesture recognition system is designed and evaluated on a publicly available database with good results as a first attempt to perform this task in the medical field. We conclude that, to recognize facial gestures in patients with facial paralysis, the severity of the damage has to be considered because paralyzed organs exhibit different behavior than do healthy ones, and any recognition system must be capable of discerning these behaviors.

Background: ‘Dating and relationship violence’ is intimate partner violence during adolescence. Among dating adolescents in England, 66–75% of girls and 32–50% of boys report victimisation. Multicomponent school-based interventions might reduce dating and relationship violence. We optimised and piloted Project Respect, a new intervention in secondary schools in England, and study methods, to assess the value of a Phase III randomised controlled trial. Objectives: To optimise Project Respect and to then conduct a pilot randomised controlled trial in southern England, addressing whether or not progression to a Phase III trial is justified in terms of prespecified criteria. To assess which of two dating and relationship violence scales is optimal, to assess response rates and to consider any necessary refinements. Design: Optimisation activities aimed at intervention development and a pilot randomised controlled trial. Setting: Optimisation in four secondary schools across southern England, varying by region and local deprivation. A pilot cluster randomised controlled trial in six other such schools (four intervention schools and two control schools), varying by region, attainment and local deprivation. Participants: School students in years 8–10 at baseline and staff. Interventions: Schools were randomised to the intervention or control arm in a 2 : 1 ratio; intervention comprised staff training, mapping ‘hotspots’ in school for dating and relationship violence, modifying staff patrols, school policy review, informing parents and carers, an application supporting student help-seeking, and a classroom curriculum for students in years 9 and 10 (including student-led campaigns). Main outcome measures: Prespecified criteria for progression to Phase III of the trial, concerning acceptability, feasibility, fidelity and response rates. Primary health outcomes were assessed using the Safe Dates and short Conflicts in Adolescent Dating Relationships Inventory measures collected and analysed by individuals who were masked to allocation. Feasibility of economic analysis was assessed. Data sources: Baseline and follow-up student and staff surveys, interviews, observations and logbooks. Results: The intervention was optimised and approved by the Study Steering Committee. The student response rates in intervention and control groups were 1057 (84.8%) and 369 (76.6%) at baseline, and 1177 (76.8%) and 352 (83.4%) at follow-up, respectively. Safe Dates and the short Conflicts in Adolescent Dating Relationships Inventory had high levels of completion and reliability. At follow-up, prevalence of past-year dating and relationship violence victimisation was around 35% (Safe Dates scale and short Conflicts in Adolescent Dating Relationships Inventory). Staff response rates were very low. Training occurred in all four schools, with suboptimal fidelity. The curriculum was delivered with optimal fidelity in three schools. Other components were delivered inconsistently. Dating and relationship violence was addressed in control schools via violence prevention and responses, but not systematically. Intervention acceptability among students and staff was mixed. An economic evaluation would be feasible. Limitations: One school did not undertake baseline surveys. Staff survey response rates were low and completion of the logbook was patchy. Conclusions: Our findings suggest that progression to a Phase III trial of this intervention is not indicated because of limited fidelity and acceptability. Future work: High prevalence of dating and relationship violence highlights the ongoing need for effective intervention. Potential intervention refinements would include more external support for schools and enhanced curriculum materials. Any future randomised controlled trials could consider having a longer lead-in from randomisation to intervention commencement, using the short Conflicts in Adolescent Dating Relationships Inventory as the primary outcome and not relying on staff surveys. Trial registration: Current Controlled Trials ISRCTN65324176. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 8, No. 5. See the NIHR Journals Library website for further project information.

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 Super Resolution 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.

Particles of diamond in the 5–100 nm size range, known as nanodiamond (ND), have shown promise as robust fluorophores for optical imaging. We demonstrate here that, due to their photostability, they are not only suitable for two-photon imaging, but also allow significant resolution enhancement when combined with computational super-resolution techniques. We observe a resolution of 42.5 nm when processing two-photon images with the Super-Resolution Radial Fluctuations algorithm. We show manipulation of the point-spread function of the microscope using adaptive optics. This demonstrates how the photostability of ND can also be of use when characterizing adaptive optics technologies or testing the resilience of super-resolution or aberration correction algorithms.

The inability to move the muscles of the face on one or both sides is known as facial paralysis, which may affect the ability of the patient to speak, blink, swallow saliva, eat, or communicate through natural facial expressions. The well-being of the patient could also be negatively affected. Computer-based systems as a means to detect facial paralysis are important in the development of standardized tools for medical assessment, treatment, and monitoring; additionally, they are expected to provide user-friendly tools for patient monitoring at home. In this work, a methodology to detect facial paralysis in a face photograph is proposed. A system consisting of three modules—facial landmark extraction, facial measure computation, and facial paralysis classification—was designed. Our facial measures aim to identify asymmetry levels within the face elements using facial landmarks, and a binary classifier based on a multi-layer perceptron approach provides an output label. The Weka suite was selected to design the classifier and implement the learning algorithm. Tests on publicly available databases reveal outstanding classification results on images, showing that our methodology that was used to design a binary classifier can be expanded to other databases with great results, even if the participants do not execute similar facial expressions.

We developed a simple, cost-effective smartphone microscopy platform for use in educational and public engagement programs. We demonstrated its effectiveness, and potential for citizen science through a national imaging initiative, EnLightenment. The cost effectiveness of the instrument allowed for the program to deliver over 500 microscopes to more than 100 secondary schools throughout Scotland, targeting 1000’s of 12-14 year olds. Through careful, quantified, selection of a high power, low-cost objective lens, our smartphone microscope has an imaging resolution of microns, with a working distance of 3 mm. It is therefore capable of imaging single cells and sub-cellular features, and retains usability for young children. The microscopes were designed in kit form and provided an interdisciplinary educational tool. By providing full lesson plans and support material, we developed a framework to explore optical design, microscope performance, engineering challenges on construction and real-world applications in life sciences, biological imaging, marine biology, art, and technology. A national online imaging competition framed EnLightenment; with over 500 high quality images submitted of diverse content, spanning multiple disciplines. With examples of cellular and sub-cellular features clearly identifiable in some submissions, we show how young public can use these instruments for research-level imaging applications, and the potential of the instrument for citizen science programs.

We developed a simple, cost-effective smartphone microscopy platform for use in educational and public engagement programs. We demonstrated its effectiveness, and potential for citizen science through a national imaging initiative, EnLightenment. The cost effectiveness of the instrument allowed for the program to deliver over 500 microscopes to more than 100 secondary schools throughout Scotland, targeting 1000’s of 12-14 year olds. Through careful, quantified, selection of a high power, low-cost objective lens, our smartphone microscope has an imaging resolution of microns, with a working distance of 3 mm. It is therefore capable of imaging single cells and sub-cellular features, and retains usability for young children. The microscopes were designed in kit form and provided an interdisciplinary educational tool. By providing full lesson plans and support material, we developed a framework to explore optical design, microscope performance, engineering challenges on construction and real-world applications in life sciences, biological imaging, marine biology, art, and technology. A national online imaging competition framed EnLightenment; with over 500 high quality images submitted of diverse content, spanning multiple disciplines. With examples of cellular and sub-cellular features clearly identifiable in some submissions, we show how young public can use these instruments for research-level imaging applications, and the potential of the instrument for citizen science programs.

Cutaneous malignant melanoma is an aggressive and potentially lethal form of skin cancer, particularly in its advanced and therapy-resistant stages, and the need for novel therapeutics and prognostic tools is acute. Incidence of melanoma has steadily increased over the past few decades, with exposure to the genome-damaging effects of ultraviolet radiation (UVR) well-recognized as a primary cause. A number of genetically-engineered mouse models (GEMMs) have been created that exhibit high incidence of spontaneous and induced forms of melanoma, and a select subset recapitulates its progression to aggressive and metastatic forms. These GEMMs hold considerable promise for providing insights into advanced stages of melanoma, such as potential therapeutic targets and prognostic markers, and as in vivo systems for testing of novel therapies. In this review, we summarize how the HGF/SF transgenic mouse has been used to reveal metastasis-regulating activity of four different genes (CDK4R24C, survivin and NME1/NME2) in the context of UV-induced melanoma. We also discuss how these models can potentially yield new strategies for clinical management of melanoma in its most aggressive forms.

The expansion of high-quality, low-cost sequencing has created an enormous opportunity to understand how genetic variants alter cellular behaviour in disease. The high diversity of mutations observed has however drawn a spotlight onto the need for predictive modelling of mutational effects on phenotype from variants of uncertain significance. This is particularly important in the clinic due to the potential value in guiding clinical diagnosis and patient treatment. Recent computational modelling has highlighted the importance of mutation induced protein misfolding as a common mechanism for loss of protein or domain function, aided by developments in methods that make large computational screens tractable. Here we review recent applications of this approach to different genes, and how they have enabled and supported subsequent studies. We further discuss developments in the approach and the role for the approach in light of increasingly high throughput experimental approaches. [ABSTRACT FROM AUTHOR]

Adolescent dating and relationship violence is associated with health harms and is an important topic for sex education. School-based interventions addressing this have been effective in the USA, but schools in England confront pressures that might hinder implementation. We assessed the feasibility of, and contextual enablers/barriers to implementing Project Respect, a whole-school intervention. We conducted a pilot trial with process evaluation in six English secondary schools. Intervention comprised: training; policy-review; mapping and patrolling 'hotspots'; parent information; help-seeking app; and a curriculum (including student-led campaigns) targeting dating violence. Process evaluation included assessments of fidelity and interviews with the trainer and school staff. Schools delivered training and lessons partially or completely and made parent and app information available. Two schools conducted policy reviews; none patrolled hotspots or implemented campaigns. Implementation was strengthened where staff saw dating violence as a priority. Delivery was undermined where staff were insufficiently involved, lacked time for planning or struggled to timetable lessons, and where new school challenges undermined engagement. School-based health interventions must work to build staff buy-in and ensure they do not overburden schools. Dating and relationship violence might best be addressed in this context as a broader aspect of sex education.

Multichannel, infinite-conjugate optical systems easily allow implementation of multiple image paths and imaging modes into a single microscope. Traditional optical alignment methods which rely on additional hardware are not always simple to implement, particularly in compact open-source microscope designs. We present here an alignment algorithm and process to position the lenses and cameras in a microscope using only image magnification measurements. We show that the resulting positioning accuracy is comparable to the axial resolution of the microscope. Ray transfer matrix analysis is used to model the imaging paths when the optics are both correctly and incorrectly aligned. This is used to derive the corresponding image magnifications. We can then extract information about the lens positions using simple image-based measurements to determine whether there is misalignment of the objective lens to sample distance (working distance) and with what magnitude and direction the objective lens needs to be adjusted. Using the M4All open-source 3D printable microscope system in combination with the OpenFlexure microscope, we validate the alignment method and highlight its usability. We provide the model and an example implementation of the algorithm as an open-source Jupyter Notebook. This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'. [ABSTRACT FROM AUTHOR]

Abstract Background The pronounced changes in reproductive hormones, such as oestradiol and progesterone, that occur during the menopause transition can contribute to increased risk of eating disorder onset or exacerbate a pre-existing eating disorder. Despite this heightened risk, there is a lack of available education and support that takes into consideration the unique challenges of experiencing an eating disorder during the menopause transition. This research aimed to qualitatively explore the perspectives of people with a lived experience of an eating disorder during the menopause transition, and to co-design a support option that addressed their unmet needs. Methods A Double Diamond co-design process was followed involving four phases: discover, define, develop, and deliver. Seventeen women in Australia with a lived experience of an eating disorder during the menopause transition participated in online workshops across the four phases to identify their unmet health educational needs in experiencing an eating disorder during this transition, develop potential solutions and ultimately deliver a prototype solution in the final phase. All online workshops were recorded, transcribed verbatim and analysed using qualitative thematic analysis. The findings from the previous phase informed the next leading to the prototype creation. Results Qualitative thematic analysis identified six major themes across the four phases; lack of awareness of the intersection of menopause and eating disorders, lack of education, limited and stigmatising services, learning from lived experience, resource impact and resource development. Conclusions Findings from this study provided preliminary acceptability of a novel online resource to address the unmet educational needs of people experiencing an eating disorder during the menopause transition. Overall positive feedback on the potential for the resource to improve knowledge and empower treatment-seeking was provided by women with lived experience.