Aiming higher : the Plymouth and Peninsula Tri-Level Model (PPM) for school/HE links : putting the university into school and community

"This report outlines an innovative, effective model of school/higher education (HE) liaison, the Plymouth & Peninsula Model (PPM). The PPM is of major national and international importance. The defining quality of PPM is that it is a genuine partnership, with parity of esteem between HEIs, schools and local authorities (LAs), supported by other major stakeholders. The PPM is based upon firm research evidence, is highly cost effective and could be rolled out nationally to cover geographically all primary and secondary schools and college grouped in consortia" - page iii

Acute parotitis due to MRSA causing Lemierre's syndrome.

We report a case of septic thrombophlebitis of the right internal jugular vein linked with right-sided acute parotitis caused by methicillin-resistant Staphylococcus aureus (MRSA) in a patient who had recently undergone a pylorus-preserving pancreaticoduodenectomy. Our case is unique because acute parotitis is a less-recognized cause of Lemierre's syndrome, never previously linked with MRSA infection in this context. We review the literature on diagnosis and management of Lemierre's syndrome caused by acute parotitis. Prompt diagnosis and aggressive antibiotics ensured a favourable outcome

Exploring the Expression of Cardiac Regulators in a Vertebrate Extremophile: The Cichlid Fish Oreochromis (Alcolapia) alcalica

Although it is widely accepted that the cellular and molecular mechanisms of vertebratecardiac development are evolutionarily conserved, this is on the basis of data from only a fewmodel organisms suited to laboratory studies. Here, we investigate gene expression during cardiacdevelopment in the extremophile, non-model fish species, Oreochromis (Alcolapia) alcalica. Wefirst characterise the early development of O. alcalica and observe extensive vascularisation across the yolk prior to hatching. We further investigate heart development by identifying andcloning O. alcalica orthologues of conserved cardiac transcription factors gata4, tbx5, and mef2cfor analysis by in situ hybridisation. Expression of these three key cardiac developmentalregulators also reveals other aspects of O. alcalica development, as these genes are expressed indeveloping blood, limb, eyes, and muscle, as well as the heart. Our data support the notion that O.alcalica is a direct-developing vertebrate that shares the highly conserved molecular regulation ofthe vertebrate body plan. However, the expression of gata4 in O. alcalica reveals interestingdifferences in the development of the circulatory system distinct from that of the well-studiedzebrafish. Understanding the development of O. alcalica embryos is an important step towardsproviding a model for future research into the adaptation to extreme conditions; this is particularlyrelevant given that anthropogenic-driven climate change will likely result in more freshwaterorganisms being exposed to less favourable conditions

Diagnosing the accretion flow in ultraluminous X-ray sources using soft X-ray atomic features

The lack of unambiguous detections of atomic features in the X-ray spectra of ultraluminous X-ray sources (ULXs) has proven a hindrance in diagnosing the nature of the accretion flow. The possible association of spectral residuals at soft energies with atomic features seen in absorption and/or emission and potentially broadened by velocity dispersion could therefore hold the key to understanding much about these enigmatic sources. Here we show for the first time that such residuals are seen in several sources and appear extremely similar in shape, implying a common origin. Via simple arguments we assert that emission from extreme colliding winds, absorption in a shell of material associated with the ULX nebula and thermal plasma emission associated with star formation are all highly unlikely to provide an origin. Whilst CCD spectra lack the energy resolution necessary to directly determine the nature of the features (i.e. formed of a complex of narrow lines or intrinsically broad lines), studying the evolution of the residuals with underlying spectral shape allows for an important, indirect test for their origin. The ULX NGC 1313 X-1 provides the best opportunity to perform such a test due to the dynamic range in spectral hardness provided by archival observations. We show through highly simplified spectral modelling that the strength of the features (in either absorption or emission) appears to anticorrelate with spectral hardness, which would rule out an origin via reflection of a primary continuum and instead supports a picture of atomic transitions in a wind or nearby material associated with such an outflow

Protocol of a feasibility randomised controlled trial of Empowered Conversations: training family carers to enhance their relationships and communication with people living with dementia. [version 1; peer review: 3 approved]

Background: Communication difficulties can cause frustration, low mood, and stress for people living with dementia and their carer. Carers should be offered training on adapting their communication skills. However, it is not common for skills-based education to examine emotional aspects of care and the effect of dementia on relationships. The Empowered Conversations (EC) training course was developed in response to a gap in service provision and has been adapted to a virtual format (Zoom). It addresses the specific psychological, relationship, and communication needs of informal and family dementia carers. The primary aim of the study is to investigate the feasibility of conducting a multi-centre randomised controlled evaluation trial of EC.  Secondary aims include exploring the acceptability of delivering the intervention online and examining the optimum way of establishing cost-effectiveness. Methods: The feasibility trial uses a pragmatic data-collector blind parallel two-group RCT design with two arms (EC intervention plus treatment as usual, and treatment as usual waitlist control). There will be a 2:1 allocation in favour of the EC-training intervention arm. 75 participants will complete baseline outcome measures exploring their role as a carer, including their physical and mental health, attitudes to caring, quality of life, and use of health and social care services. These will be repeated after six-months. Participants allocated to the treatment group who complete the course will be invited to participate in a qualitative interview discussing their experience of EC. Discussion: The study will investigate recruitment pathways (including facilitators and barriers to recruitment), estimate retention levels and response rates to questionnaires, obtain additional evidence regarding proof of concept, and consider the most appropriate primary outcome measures and methods for evaluating cost-effectiveness. The results of the feasibility study will be used to inform the development of a multicentre randomised controlled trial in the United Kingdom. Registration: ISRCTN15261686 (02/03/2022

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

InterPro in 2017-beyond protein family and domain annotations

InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year