The streptococcal collagen-like protein-1 (Scl1) is a multifunctional adhesin in extracellular matrix interactions, biofilm formation, and host colonization by group A Streptococcus

Group A Streptococcus (GAS) is responsible for over 100 million skin infections annually that may lead to invasive episodes and autoimmune sequelaes. Wounds and unapparent skin infringements are susceptible to the introduction of GAS and serve as a portal of entry. The nutritional nature of a wound and the accessibility to exposed host cell surfaces and extracellular matrix components create a model milieu for successful host colonization and potential biofilm formation. The initiation of biofilm is often mediated by bacterial surface adhesins and has been shown to interfere with wound healing by blocking critical host cellular interactions. However, the underlying molecular mechanisms supporting this impediment of wound healing are not completely understood. Here, we characterize the GAS surface adhesin, streptococcal collagen-like protein-1 (Scl1), and its interaction with extracellular matrix components and contribution to GAS biofilm formation. Scl1 has been detected in all GAS strains and extends from the GAS surface as a homotrimeric protein composed of a collagen-like domain, structurally similar to mammalian collagen, and an adjacent amino-terminal non-collagenous variable domain. The current work (i) identifies that the Scl1 variable domain binds to extracellular matrix proteins, cellular fibronectin and laminin and contributes to GAS adherence and internalization (ii) demonstrates that the Scl1 protein is an important determinant of GAS biofilm formation on untreated and ECM-deposited surfaces, and (iii) characterizes a novel molecular mechanism by which GAS utilizes the Scl1 protein to specifically target the EDA-containing variant of cellular fibronectin predominantly expressed at the site of injured tissue in order to secure host colonization and biofilm formation. In total, these studies further demonstrate the importance of the Scl1 protein in GAS pathogenesis

A UML profile to support requirements engineering with KAOS

One of the most important approaches to requirements engineering of the last ten years is the KAOS model. The authors introduce a profile that allows the KAOS model to be represented in the UML. The paper includes an informal presentation of the profile together with a full account of the new stereotypes and tags. They also outline an integration of requirements models with lower level design models in the UML, leading to a uniform and comprehensive specification document. A UML profile can increase the usefulness of KAOS. A method can be truly successful only if a large number of professionals are sufficiently convinced of its potential to use it in industrial cases. Use of the UML to support requirements engineering with KAOS may help achieve this end

Eligibility screening older research participants using remote cognitive assessment—experiences and reflections from a primary care randomised controlled trial

Background The COVID-19 pandemic forced many research teams to adjust the way they conduct studies, including moving to remote delivery of some or all of their recruitment and data collection processes. The Montreal Cognitive Assessment (MoCA) is widely used in research and is available in multiple formats for different groups and assessment settings. Here, we reflect on our experiences of administering the MoCA Blind/Telephone as part of the initial telephone eligibility check for participation in a randomised controlled trial with community-dwelling older people with frailty. Main body In response to COVID-19, a number of changes were made to the trial’s screening and recruitment procedures, to minimise the amount of time the researchers would spend in the participants’ homes when recruitment began in May 2021. One of the changes was for the researchers to conduct a cognitive assessment for eligibility during an initial telephone call, rather than during the subsequent home visit for consent and baseline data collection. We found that in comparison with conducting the assessment in-person, telephone administration caused uncertainty for the researchers about whether participants were struggling to answer questions due to cognition or hearing impairment. Some participants experienced practical difficulties when combining holding a telephone and completing one of the assessment items. It was hard for the researchers to judge the emotional impact that undertaking the assessment was having on the older people on the telephone, without visual warning signs of fatigue or mood. We discuss the potential impact of these issues on trial recruitment and participant engagement, and the feasibility of videoconferencing as an alternative method of conducting the MoCA. Conclusion The MoCA is a useful tool when cognitive impairment is part of screening and data collection and it is helpful to have the option to use the test remotely. However, as we have found, telephone testing is not always straightforward. Researchers should weigh up the pros and cons for each individual study, especially those involving older adults. If choosing remote methods, consider the practicality of using videoconferencing and think about the possible impact of telephone assessment on the relationship with the (potential) research participants. Trial registration Personalised care planning for older people with frailty ISRCTN16123291 28/08/2020

Multidisciplinary team decision-making in cancer and the absent patient: a qualitative study

Objective To critically examine the process of multidisciplinary team (MDT) decision-making with a particular focus on patient involvement. Design Ethnographic study using direct non-participant observation of 35 MDT meetings and 37 MDT clinics, informal interviews and formal, semistructured interviews with 20 patients and 9 MDT staff members. Setting Three head and neck cancer centres in the north of England. Participants Patients with a diagnosis of new or recurrent head and neck cancer and staff members who attend the head and neck cancer MDT. Results Individual members of the MDT often have a clear view of which treatment they consider to be ‘best’ in any clinical situation. When disagreement occurs, the MDT has to manage how it presents this difference of opinion to the patient. First, this is because the MDT members recognise that the clinician selected to present the treatment choice to the patient may ‘frame’ their description of the treatment options to fit their own view of best. Second, many MDT members feel that any disagreement and difference of opinion in the MDT meeting should be concealed from the patient. This leads to much of the work of decision-making occurring in the MDT meeting, thus excluding the patient. MDT members seek to counteract this by introducing increasing amounts of information about the patient into the MDT meeting, thus creating an ‘evidential patient’. Often, only highly selected or very limited information of this type can be available or known and it can easily be selectively reported in order to steer the discussion in a particular direction

The cost of community research—recruiting community-dwelling participants to a feasibility primary care cluster randomised controlled trial

Background To support a robust evidence base for the organisation and provision of community-delivered health services for older people, clinical trials need to be designed to account for community-based participant recruitment. There is currently little reported information available on the time and cost of recruiting community-dwelling older people, which makes the completion of cost attribution documentation problematic when applying for research funding. Main body We aimed to establish the amount of researcher time it takes to recruit community-dwelling older people to a feasibility primary care cluster randomised controlled trial, including collecting baseline data. The trial was part of a programme of work investigating an intervention to improve the quality of life for older people with frailty. Two researchers conducting home visits to recruit and collect baseline data from participants recorded the time spent on travelling to and from the visit, at the visit itself and any associated administration. The median total researcher activity time per visit was 148 min. We discuss the various elements of recruitment and data collection activity and the factors that impacted the length of time taken, including location, individuals’ capacity and cognition, hearing and visual impairment and the desire for social contact. Conclusion Studies cannot reach their recruitment targets if they are unrealistically planned and resourced. We recommend that trials recruiting older people in the community allocate two and a half hours of researcher time per person, on average, for consent, baseline data collection, travel and administration. We acknowledge that a variety of different factors will mean that researcher activity will vary between different community-based trials. Our findings give a good starting point for timing calculations, and evidence on which to base the justification of research activity costings. Trial registration Personalised care planning for older people with frailty ISRCTN12363970. 08/11/2018

Estimating the incidence, prevalence and true cost of asthma in the UK: secondary analysis of national stand-alone and linked databases in England, Northern Ireland, Scotland and Wales-a study protocol.

INTRODUCTION: Asthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care. METHODS AND ANALYSIS: Secondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates. ETHICS AND DISSEMINATION: Approvals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map

State-to-State Rotational Rate Constants for CO+He: Infrared Double Resonance Measurements and Simulation of the Data Using the SAPT Theoretical Potential Energy Surface

An extensive data set of 54 time-resolved pump-probe measurements was used to examine CO+He rotational energy transfer within the CO v=2 rotational manifold. Rotational levels in the range Ji=2-9 were excited and collisional energy transfer of population to the levels Jf=1-10 was monitored. The resulting data set was analyzed by fitting to numerical solutions of the master equation. State-to-state rate constant matrices were generated using fitting law functions and ab initio theoretical calculations that employed the SAPT potential energy surface of Heijmen et al. [J. Chem. Phys. 107, 9921 (1997)]. Fitting laws based on the modified exponential gap (MEG), statistical power exponential gap (SPEG), and energy corrected sudden with exponential power (ECS-EP) models all yielded acceptable simulations of the kinetic data, as did the theoretical rate constants. However, the latter were unique in their ability to reproduce both our kinetic data and the pressure broadening coefficients for CO+He. These results provide an impressive demonstration of the quality of the symmetry adapted perturbation theory (SAPT) potential energy surface

Isolation of Metrosideros (`Ohi`a) Taxa on O`ahu Increases with Elevation and Extreme Environments

Species radiations should be facilitated by short generation times and limited dispersal among discontinuous populations. Hawaii’s hyper-diverse, landscape-dominant tree, Metrosideros, is unique among the islands’ radiations for its massive populations that occur continuously over space and time within islands, its exceptional capacity for gene flow by both pollen and seed, and its extended life span (ca. \u3e650 years). Metrosideros shows the greatest phenotypic and microsatellite DNA diversity on O`ahu, where taxa occur in tight sympatry or parapatry in mesic and montane wet forest on 2 volcanoes. We document the nonrandom distributions of 12 taxa (including unnamed morphotypes) along elevation gradients, measure phenotypes of ~6-year-old common-garden plants of 8 taxa to verify heritability of phenotypes, and examine genotypes of 476 wild adults at 9 microsatellite loci to compare the strengths of isolation across taxa, volcanoes, and distance. All 8 taxa retained their diagnostic phenotypes in the common garden. Populations were isolated by taxon to a range of degrees (pairwise FST between taxa: 0.004–0.267), and there was no pattern of isolation by distance or by elevation; however, significant isolation between volcanoes was observed within monotypic species, suggesting limited gene flow between volcanoes. Among the infraspecific taxa of Metrosideros polymorpha, genetic diversity and isolation significantly decreased and increased, respectively, with elevation. Overall, 5 of the 6 most isolated taxa were associated with highest elevations or otherwise extreme environments. These findings suggest a principal role for selection in the origin and maintenance of the exceptional diversity that occurs within continuous Metrosideros stands on O`ahu