Patient and Public Involvement (PPI) report for proposed study: Listen and Learn

Context: Patient and Public Involvement (PPI) work was undertaken to engage relevant stakeholders (residents, family members, volunteers and staff) in order to incorporate their experiences and insights into our NIHR grant proposal, “Listen and learn”. The proposed research study aims to explore the use of resident feedback in care homes to embolden person-centred care. NIHR RDS formally funded PPI activity in the NW throughout the summer of 2016. Using similar methods, researchers from project teams across the UK also informally engaged with residents, care managers, volunteers and family members in their networks to provide perspectives from across the UK. This report focuses on the NW engagement but is reflective of the wider, informal engagements. Aims: The PPI activity was undertaken in order to learn from older people, their formal carers and families/relatives: 1. The relevance to them of the proposed research question 2. How best to attract, recruit and retain people as research participants 3. Identification of ethical issues and concerns 4. How best to support staff and volunteers during research 5. How best to communicate the difference (impact) our project makes People told us: 1.Volunteers are scarce, so need to scope availability. For volunteers, safeguarding and capacity to speak up about concerns deemed important. Settings will require bespoke engagement approaches. 2.Methods should be mixed, e.g. visual/diaries; non-verbal communication/diversity addressed, e.g. people with dementia need a skilled approach; sufficient time to develop rapport. 3.Impacts to focus on people, not only institutions; sufficient time needed to show impact. Dissemination should consider adjustments for people with disabilities to enable involvement. (Full report available via MMU e-repository

Salford postgraduate annual research conference (SPARC) 2012 proceedings

These proceedings bring together a selection of papers from the 2012 Salford Postgraduate Annual Research Conference (SPARC). They reflect the breadth and diversity of research interests showcased at the conference, at which over 130 researchers from Salford, the North West and other UK universities presented their work. 21 papers are collated here from the humanities, arts, social sciences, health, engineering, environment and life sciences, built environment and business

Characterisation of carbon nanotubes in the context of toxicity studies

Nanotechnology has the potential to revolutionise our futures, but has also prompted concerns about the possibility that nanomaterials may harm humans or the biosphere. The unique properties of nanoparticles, that give them novel size dependent functionalities, may also have the potential to cause harm. Discrepancies in existing human health and environmental studies have shown the importance of good quality, well-characterized reference nanomaterials for toxicological studies

DNA adducts in human urinary bladder and other tissues.

Tobacco smoking is associated with an increased risk of cancer in a number of organs, including bladder and lung. Tobacco smoke contains at least 50 known chemical carcinogens that exert their biological effects through their covalent binding to cellular DNA. Examining human DNA for the presence of altered nucleotides is a means of monitoring exposure to genotoxic chemicals. DNA isolated from 73 human bladder biopsies has been analyzed by 32P-postlabeling for the presence of aromatic/hydrophobic adducts. Butanol extraction of DNA digests resulted in up to a 3-fold greater recovery of adducts than nuclease P1 digestion. Among 16 nonsmokers, adduct levels were in the range 3.2-20.8/10(8) nucleotides (mean 9.7). Eight ex-smokers had values in the range 2.6-12.3 (mean 7.1). Thirteen smokers had adduct levels between 1.3 and 26.7 adducts/10(8) nucleotides (mean 9.5, not different from nonsmokers). Six cigar smokers had higher levels of adducts (mean 12.1, range 7.3-15.0), but pipe smokers did not (five samples, mean 8.6, range 2.9-12.7). A further 8 samples from nonsmokers and 17 from smokers were examined in more detail. Although most of the DNA binding appears not to be smoking related, the levels of one adduct were found to be on average 2-fold higher in smokers (p < 0.005, one-tailed t test). Studies on tissues of the respiratory tract demonstrate a correlation between DNA adduct levels and exposure to tobacco smoke. Evidence to date on the influence of smoking on adducts in peripheral blood cells is equivocal; some studies demonstrate a significant effect, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS

A tectonic-rules-based mantle reference frame since 1 billion years ago – implications for supercontinent cycles and plate–mantle system evolution

Understanding the long-term evolution of Earth's plate–mantle system is reliant on absolute plate motion models in a mantle reference frame, but such models are both difficult to construct and controversial. We present a tectonic-rules-based optimization approach to construct a plate motion model in a mantle reference frame covering the last billion years and use it as a constraint for mantle flow models. Our plate motion model results in net lithospheric rotation consistently below 0.25∘ Myr−1, in agreement with mantle flow models, while trench motions are confined to a relatively narrow range of −2 to +2 cm yr−1 since 320 Ma, during Pangea stability and dispersal. In contrast, the period from 600 to 320 Ma, nicknamed the “zippy tricentenary” here, displays twice the trench motion scatter compared to more recent times, reflecting a predominance of short and highly mobile subduction zones. Our model supports an orthoversion evolution from Rodinia to Pangea with Pangea offset approximately 90∘ eastwards relative to Rodinia – this is the opposite sense of motion compared to a previous orthoversion hypothesis based on paleomagnetic data. In our coupled plate–mantle model a broad network of basal mantle ridges forms between 1000 and 600 Ma, reflecting widely distributed subduction zones. Between 600 and 500 Ma a short-lived degree-2 basal mantle structure forms in response to a band of subduction zones confined to low latitudes, generating extensive antipodal lower mantle upwellings centred at the poles. Subsequently, the northern basal structure migrates southward and evolves into a Pacific-centred upwelling, while the southern structure is dissected by subducting slabs, disintegrating into a network of ridges between 500 and 400 Ma. From 400 to 200 Ma, a stable Pacific-centred degree-1 convective planform emerges. It lacks an antipodal counterpart due to the closure of the Iapetus and Rheic oceans between Laurussia and Gondwana as well as due to coeval subduction between Baltica and Laurentia and around Siberia, populating the mantle with slabs until 320 Ma when Pangea is assembled. A basal degree-2 structure forms subsequent to Pangea breakup, after the influence of previously subducted slabs in the African hemisphere on the lowermost mantle structure has faded away. This succession of mantle states is distinct from previously proposed mantle convection models. We show that the history of plume-related volcanism is consistent with deep plumes associated with evolving basal mantle structures. This Solid Earth Evolution Model for the last 1000 million years (SEEM1000) forms the foundation for a multitude of spatio-temporal data analysis approaches

Structural Changes of the Paraflagellar Rod during Flagellar Beating in Trypanosoma cruzi

, the agent of Chagas disease, is a protozoan member of the Kinetoplastidae family characterized for the presence of specific and unique structures that are involved in different cell activities. One of them is the paraflagellar rod (PFR), a complex array of filaments connected to the flagellar axoneme. Although the function played by the PFR is not well established, it has been shown that silencing of the synthesis of its major proteins by either knockout of RNAi impairs and/or modifies the flagellar motility.Here, we present results obtained by atomic force microscopy (AFM) and transmission electron microscopy (TEM) of replicas of quick-frozen, freeze-fractured, deep-etched and rotary-replicated cells to obtain detailed information of the PFR structures in regions of the flagellum in straight and in bent state. The images obtained show that the PFR is not a fixed and static structure. The pattern of organization of the PFR filament network differs between regions of the flagellum in a straight state and those in a bent state. Measurements of the distances between the PFR filaments and the filaments that connect the PFR to the axoneme as well as of the angles between the intercrossed filaments supported this idea.Graphic computation based on the information obtained allowed the proposal of an animated model for the PFR structure during flagellar beating and provided a new way of observing PFR filaments during flagellar beating

Plasma levels of alpha1-antichymotrypsin and secretory leukocyte proteinase inhibitor in healthy and chronic obstructive pulmonary disease (COPD) subjects with and without severe α1-antitrypsin deficiency

BACKGROUND: Individuals with severe Z α1-antitrypsin (AAT) deficiency have a considerably increased risk of developing chronic obstructive lung disease (COPD). It has been hypothesized that compensatory increases in levels of other protease inhibitors mitigate the effects of this AAT deficiency. We analysed plasma levels of AAT, α1-antichymotrypsin (ACT) and secretory leukocyte protease inhibitor (SLPI) in healthy (asymptomatic) and COPD subjects with and without AAT deficiency. METHODS: Studied groups included: 71 asymptomatic AAT-deficient subjects (ZZ, n = 48 and SZ, n = 23, age 31 ± 0.5) identified during Swedish neonatal screening for AAT deficiency between 1972 and 1974; age-matched controls (MM, n = 57, age 30.7 ± 0.6); older asymptomatic ZZ (n = 10); healthy MM (n = 20, age 53 ± 9.6); and COPD patients (ZZ, n = 10, age 47.4 ± 11 and MM, n = 10, age 59.4 ± 6.7). Plasma levels of SLPI, AAT and ACT were analysed using ELISA and immunoelectrophoresis. RESULTS: No significant difference was found in plasma ACT and SLPI levels between the healthy MM and the ZZ or SZ subjects in the studied groups. Independent of the genetic variant, subjects with COPD (n = 19) had elevated plasma levels of SLPI and ACT relative to controls (n = 153) (49.5 ± 7.2 vs 40.7 ± 9.1 ng/ml, p < 0.001 and 0.52 ± 0.19 vs 0.40 ± 0.1 mg/ml, p < 0.05, respectively). CONCLUSION: Our findings show that plasma levels of ACT and SLPI are not elevated in subjects with genetic AAT deficiency compared MM controls and do not appear to compensate for the deficiency of plasma AAT

Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers

<p>Abstract</p> <p>Background</p> <p>The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?</p> <p>Methods</p> <p>Using microarray analysis, with TaqMan RT-PCR confirmation, we assessed oxidant-related gene expression in small airway epithelium and alveolar macrophages from the same healthy nonsmoker and smoker individuals.</p> <p>Results</p> <p>Of 155 genes surveyed, 87 (56%) were expressed in both cell populations in nonsmokers, with higher expression in alveolar macrophages (43%) compared to airway epithelium (24%). In smokers, there were 15 genes (10%) up-regulated and 7 genes (5%) down-regulated in airway epithelium, but only 3 (2%) up-regulated and 2 (1%) down-regulated in alveolar macrophages. Pathway analysis of airway epithelium showed oxidant pathways dominated, but in alveolar macrophages immune pathways dominated.</p> <p>Conclusion</p> <p>Thus, the response of different cell-types with an identical genome exposed to the same stress of smoking is different; responses of alveolar macrophages are more subdued than those of airway epithelium. These findings are consistent with the observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to smoking.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: NCT00224185 and NCT00224198</p

TbUNC119 and Its Binding Protein Complex Are Essential for Propagation, Motility, and Morphogenesis of Trypanosoma brucei Procyclic Form Cells

Flagellum-mediated motility of Trypanosoma brucei is considered to be essential for the parasite to complete stage development in the tsetse fly vector, while the mechanism by which flagellum-mediated motility is controlled are not fully understood. We thus compared T. brucei whole gene products (amino acid sequence) with Caenorhabditis elegans UNC (uncoordinated) proteins, in order to find uncharacterized motility-related T. brucei genes. Through in silico analysis, we found 88 gene products which were highly similar to C. elegans UNC proteins and categorized them as TbCEUN (T. brucei gene products which have high similarity to C. elegans UNC proteins). Approximately two thirds of the 88 TbCEUN gene products were kinesin-related molecules. A gene product highly similar to C. elegans UNC119 protein was designated as TbUNC119. RNAi-mediated depletion of TbUNC119 showed no apparent phenotype. However, knock-down analysis of both TbUNC119 and its binding protein (TbUNC119BP) which was found by yeast two-hybrid analysis showed characteristic phenotypes, including reduced motility, morphological change (extended cell shape), and cellular apoptosis. Based on the observed phenotypes, possible function of the TbUNC119 and TbUNC119BP is discussed

Translating Marine Animal Tracking Data into Conservation Policy and Management

There have been efforts around the globe to track individuals of many marine species and assess their movements and distribution with the putative goal of supporting their conservation and management. Determining whether, and how, tracking data have been successfully applied to address real-world conservation issues is however difficult. Here, we compile a broad range of case studies from diverse marine taxa to show how tracking data have helped inform conservation policy and management, including reductions in fisheries bycatch and vessel strikes, and the design and administration of marine protected areas and important habitats. Using these examples, we highlight pathways through which the past and future investment in collecting animal tracking data might be better used to achieve tangible conservation benefits