Multidisciplinary team (MDT) meetings are assumed to produce better decisions and are extensively used to manage chronic disease in the National Health Service (NHS). However, evidence for their effectiveness is mixed. Our objective was to investigate determinants of MDT effectiveness by examining factors influencing the implementation of MDT treatment plans. This is a proxy measure of effectiveness, because it lies on the pathway to improvements in health, and reflects team decision making which has taken account of clinical and non-clinical information. Additionally, this measure can be compared across MDTs for different conditions.

Increasingly, women elect breast reconstruction after mastectomy. However, their expectations of surgery are often not met, and dissatisfaction with outcome and ongoing psychosocial concerns and distress are common. We developed a patient-centered intervention, PEGASUS:(Patients' Expectations and Goals: Assisting Shared Understanding of Surgery) which supports shared decision making by helping women clarify their own, individual goals about reconstruction so that they can discuss these with their surgeon. Our acceptability/feasibility work has shown it is well received by patients and health professionals alike. We now need to establish whether PEGASUS improves patients' experiences of breast reconstruction decision making and outcomes. The purpose of this study is, therefore, to examine the effectiveness of PEGASUS, an intervention designed to support shared decision making about breast reconstruction.

Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care.

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.

The anterior temporal lobe (ATL) is considered a crucial area for the representation of transmodal concepts. Recent evidence suggests that specific regions within the ATL support the representation of individual object concepts, as shown by studies combining multivariate analysis methods and explicit measures of semantic knowledge. This research looks to further our understanding by probing conceptual representations at a spatially and temporally resolved neural scale. Representational similarity analysis was applied to human intracranial recordings from anatomically defined lateral to medial ATL sub-regions. Neural similarity patterns were tested against semantic similarity measures, where semantic similarity was defined by a hybrid corpus-based and feature-based approach. Analyses show that the perirhinal cortex, in the medial ATL, significantly related to semantic effects around 200 to 400 ms, and were greater than more lateral ATL regions. Further, semantic effects were present in low frequency (theta and alpha) oscillatory phase signals. These results provide converging support that more medial regions of the ATL support the representation of basic-level visual object concepts within the first 400 ms, and provide a bridge between prior fMRI and MEG work by offering detailed evidence for the presence of conceptual representations within the ATL.

Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF.

Visual object recognition has been traditionally conceptualised as a predominantly feedforward process through the ventral visual pathway. While feedforward artificial neural networks (ANNs) can achieve human-level classification on some image-labelling tasks, it's unclear whether computational models of vision alone can accurately capture the evolving spatiotemporal neural dynamics. Here, we probe these dynamics using a combination of representational similarity and connectivity analyses of fMRI and MEG data recorded during the recognition of familiar, unambiguous objects. Modelling the visual and semantic properties of our stimuli using an artificial neural network as well as a semantic feature model, we find that unique aspects of the neural architecture and connectivity dynamics relate to visual and semantic object properties. Critically, we show that recurrent processing between the anterior and posterior ventral temporal cortex relates to higher-level visual properties prior to semantic object properties, in addition to semantic-related feedback from the frontal lobe to the ventral temporal lobe between 250 and 500 ms after stimulus onset. These results demonstrate the distinct contributions made by semantic object properties in explaining neural activity and connectivity, highlighting it as a core part of object recognition not fully accounted for by current biologically inspired neural networks.

Chronic airway infection contributes to the underlying pathogenesis of non-cystic fibrosis bronchiectasis (NCFBr). In contrast to other chronic airway infections, associated with COPD and CF bronchiectasis, where polymicrobial communities have been implicated in lung damage due to the vicious circle of recurrent bacterial infections and inflammation, there is sparse information on the composition of bacterial communities in NCFBr. Seventy consecutive patients were recruited from an outpatient adult NCFBr clinic. Bacterial communities in sputum samples were analysed by culture and pyrosequencing approaches. Bacterial sequences were analysed using partial least square discrimination analyses to investigate trends in community composition and identify those taxa that contribute most to community variation.

Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age <18 years; and 3) patients who are unable or unwilling to provide informed consent. The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications. The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials.

To characterise Pseudomonas aeruginosa populations during chronic lung infections of non-cystic fibrosis bronchiectasis patients, we used whole-genome sequencing to 1) assess the diversity of P. aeruginosa and the prevalence of multilineage infections; 2) seek evidence for cross-infection or common source acquisition; and 3) characterise P. aeruginosa adaptations.189 isolates, obtained from the sputa of 91 patients attending 16 adult bronchiectasis centres in the UK, were whole-genome sequenced.Bronchiectasis isolates were representative of the wider P. aeruginosa population. Of 24 patients from whom multiple isolates were examined, there were seven examples of multilineage infections, probably arising from multiple infection events. The number of nucleotide variants between genomes of isolates from different patients was in some cases similar to the variations observed between isolates from individual patients, implying the possible occurrence of cross-infection or common source acquisition.Our data indicate that during infections of bronchiectasis patients, P. aeruginosa populations adapt by accumulating loss-of-function mutations, leading to changes in phenotypes including different modes of iron acquisition and variations in biofilm-associated polysaccharides. The within-population diversification suggests that larger scale longitudinal surveillance studies will be required to capture cross-infection or common source acquisition events at an early stage.

To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics.

Background: The environments that we live in impact on our ability to recognise objects, with recognition being facilitated when objects appear in expected locations (congruent) compared to unexpected locations (incongruent). However, these findings are based on experiments where the object is isolated from its environment. Moreover, it is not clear which components of the recognition process are impacted by the environment. In this experiment, we seek to examine the impact real world environments have on object recognition. Specifically, we will use mobile electroencephalography (mEEG) and augmented reality (AR) to investigate how the visual and semantic processing aspects of object recognition are changed by the environment. Methods: We will use AR to place congruent and incongruent virtual objects around indoor and outdoor environments. During the experiment a total of 34 participants will walk around the environments and find these objects while we record their eye movements and neural signals. We will perform two primary analyses. First, we will analyse the event-related potential (ERP) data using paired samples t-tests in the N300/400 time windows in an attempt to replicate congruency effects on the N300/400. Second, we will use representational similarity analysis (RSA) and computational models of vision and semantics to determine how visual and semantic processes are changed by congruency. Conclusions: Based on previous literature, we hypothesise that scene-object congruence would facilitate object recognition. For ERPs, we predict a congruency effect in the N300/N400, and for RSA we predict that higher level visual and semantic information will be represented earlier for congruent scenes than incongruent scenes. By collecting mEEG data while participants are exploring a real-world environment, we will be able to determine the impact of a natural context on object recognition, and the different processing stages of object recognition.

Recent work in cognitive and systems neuroscience has suggested that the hippocampus might support planning, imagination, and navigation by forming cognitive maps that capture the abstract structure of physical spaces, tasks, and situations. Navigation involves disambiguating similar contexts, and the planning and execution of a sequence of decisions to reach a goal. Here, we examine hippocampal activity patterns in humans during a goal-directed navigation task to investigate how contextual and goal information are incorporated in the construction and execution of navigational plans. During planning, hippocampal pattern similarity is enhanced across routes that share a context and a goal. During navigation, we observe prospective activation in the hippocampus that reflects the retrieval of pattern information related to a key-decision point. These results suggest that, rather than simply representing overlapping associations or state transitions, hippocampal activity patterns are shaped by context and goals.

The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes.

Many theoretical models suggest that neural oscillations play a role in learning or retrieval of temporal sequences, but the extent to which oscillations support sequence representation remains unclear. To address this question, we used scalp electroencephalography (EEG) to examine oscillatory activity over learning of different object sequences. Participants made semantic decisions on each object as they were presented in a continuous stream. For three "Consistent" sequences, the order of the objects was always fixed. Activity during Consistent sequences was compared to "Random" sequences that consisted of the same objects presented in a different order on each repetition. Over the course of learning, participants made faster semantic decisions to objects in Consistent, as compared to objects in Random sequences. Thus, participants were able to use sequence knowledge to predict upcoming items in Consistent sequences. EEG analyses revealed decreased oscillatory power in the theta (4-7 Hz) band at frontal sites following decisions about objects in Consistent sequences, as compared with objects in Random sequences. The theta power difference between Consistent and Random only emerged in the second half of the task, as participants were more effectively able to predict items in Consistent sequences. Moreover, we found increases in parieto-occipital alpha (10-13 Hz) and beta (14-28 Hz) power during the pre-response period for objects in Consistent sequences, relative to objects in Random sequences. Linear mixed effects modeling revealed that single trial theta oscillations were related to reaction time for future objects in a sequence, whereas beta and alpha oscillations were only predictive of reaction time on the current trial. These results indicate that theta and alpha/beta activity preferentially relate to future and current events, respectively. More generally our findings highlight the importance of band-specific neural oscillations in the learning of temporal order information.

Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis (CF) patients and causes a wide range of infections among other susceptible populations. Its inherent resistance to many antimicrobials also makes it difficult to treat infections with this pathogen. Recent evidence has highlighted the diversity of this species, yet despite this, the majority of studies on virulence and pathogenesis focus on a small number of strains. There is a pressing need for a P. aeruginosa reference panel to harmonize and coordinate the collective efforts of the P. aeruginosa research community. We have collated a panel of 43 P. aeruginosa strains that reflects the organism's diversity. In addition to the commonly studied clones, this panel includes transmissible strains, sequential CF isolates, strains with specific virulence characteristics, and strains that represent serotype, genotype or geographic diversity. This focussed panel of P. aeruginosa isolates will help accelerate and consolidate the discovery of virulence determinants, improve our understanding of the pathogenesis of infections caused by this pathogen, and provide the community with a valuable resource for the testing of novel therapeutic agents.

Anxiety and depression are common co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Serious implications can result from psychological difficulties in COPD including reduced survival, lower quality of life, and reduced physical and social functioning, increased use of health care resources and are associated with unhealthy behaviours such as smoking. Cognitive behavioural therapy (CBT) is a psychological intervention which is recommended for the treatment of many mental health problems including anxiety and depression. Unfortunately access to trained CBT therapists is limited. The aim of this study is to test the hypothesis that CBT delivered by respiratory nurses is effective in the COPD population. In this paper the design of the Newcastle Chronic Obstructive Pulmonary Disease Cognitive Behavioural Therapy Study (Newcastle COPD CBT Care Study) is described.

To respond appropriately to objects, we must process visual inputs rapidly and assign them meaning. This involves highly dynamic, interactive neural processes through which information accumulates and cognitive operations are resolved across multiple time scales. However, there is currently no model of object recognition which provides an integrated account of how visual and semantic information emerge over time; therefore, it remains unknown how and when semantic representations are evoked from visual inputs. Here, we test whether a model of individual objects--based on combining the HMax computational model of vision with semantic-feature information--can account for and predict time-varying neural activity recorded with magnetoencephalography. We show that combining HMax and semantic properties provides a better account of neural object representations compared with the HMax alone, both through model fit and classification performance. Our results show that modeling and classifying individual objects is significantly improved by adding semantic-feature information beyond ∼200 ms. These results provide important insights into the functional properties of visual processing across time.

Good practice guidelines recommend that women who undergo mastectomy are offered reconstructive surgery. However, many who choose this option report a degree of decisional regret and dissatisfaction because their pre-surgical expectations were not met. This paper reports an acceptability study of a new intervention (PEGASUS) that aims to support shared decision-making by eliciting women's pre-surgical expectations and setting patient-centred goals. Eighteen women contemplating breast reconstruction completed the PEGASUS intervention. Semi-structured interviews were conducted with 12 women and 3 health professionals to explore their experiences of using PEGASUS. Interview transcripts were subjected to a thematic analysis, and a content analysis was conducted on 79 goals that the 18 women identified. Feedback was extremely positive--women found that completing PEGASUS alongside a discussion with a specially trained health professional helped them prepare for the surgical consultation and increased their trust in their surgeon. Staff reported that PEGASUS facilitated patient-centred discussions and informed the decisions made about potential surgery. This preliminary study suggests that this novel intervention is acceptable to patients and health professionals alike. Further work is needed to evaluate its efficacy and then its effectiveness with a larger sample of women, and its potential use with other patient groups.

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis. Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study. 60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g(-1) (range -9.78-5.02 log10 CFU·g(-1))) compared with placebo (-0.27 log10 CFU·g(-1) (range -7.96-5.25 log10 CFU·g(-1))); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low. Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.