Iron isotope tracing of mantle heterogeneity within the source regions of oceanic basalts

Mineralogical variations in the Earth's mantle and the relative proportions of peridotitic versus enriched and potentially crustally-derived pyroxenitic domains within the mantle have important implications for mantle dynamics, magma generation, and the recycling of surface material back into the mantle. Here we present iron (Fe) stable isotope data (δ57Fe, deviation in 57Fe/54Fe from the IRMM-014 standard in parts per thousand) for peridotite and garnet–pyroxenite xenoliths from Oahu, Hawaii and explore Fe isotopes as tracer of both peridotitic and pyroxenitic components in the source regions of oceanic basalts. The pyroxenites have δ57Fe values that are heavy (0.10 to 0.27‰) relative to values for mid-ocean ridge and ocean island basalts (MORB; OIB; View the MathML sourceδFe57∼0.16‰) and the primitive mantle (PM; View the MathML sourceδFe57∼0.04‰). Pyroxenite δ57Fe values are positively correlated with bulk pyroxenite titanium and heavy rare earth element (REE) abundances, which can be interpreted in terms of stable isotope fractionation during magmatic differentiation and pyroxene cumulate formation. In contrast, the peridotites have light δ57Fe values (−0.34 to 0.14‰) that correlate negatively with degree of melt depletion and radiogenic hafnium isotopes, with the most depleted samples possessing the most radiogenic Hf isotope compositions and lightest δ57Fe values. While these correlations are broadly consistent with a scenario of Fe isotope fractionation during partial melting, where isotopically heavy Fe is extracted into the melt phase, leaving behind low-δ57Fe peridotite residues, the extent of isotopic variation is far greater than predicted by partial melting models. One possibility is derivation of the samples from a heterogeneous source containing both light-δ57Fe (relative to PM) and heavy-δ57Fe components. While pyroxenite is a viable explanation for the heavy-δ57Fe component, the origin of the depleted light-δ57Fe component is more difficult to explain, as melting models predict that even large (>30%) degrees of melt extraction do not generate strongly fractionated residues. Multiple phases of melt extraction or other processes, such as metasomatism, melt percolation or the assimilation of xenocrystic olivine with light δ57Fe values may need to be invoked to explain these light δ57Fe values; a caveat to this is that these processes must either preserve, or generate correlations between δ57Fe and Hf isotopes. Published variations in δ57Fe in mantle melting products, such as MORB and OIB, are also greater than predicted by melting models assuming derivation from δ57Fe-homogeneous mantle. For example, OIB from the Society and Cook-Austral islands, which have radiogenic Pb and Sr isotope compositions indicative of recycled components such as subduction modified, low-Pb oceanic crust and terrigenous sediments have heavy mean δ57Fe values (∼0.21‰∼0.21‰) significantly distinct to those of other OIB and MORB, which could explained by the presence of heavy-δ57Fe pyroxenite cumulate or pyroxenitic melt components, whereas large degree partial melts, such as komatiites and boninites, display light Fe-isotopic compositions which may reflect sampling of refractory, light-δ57Fe mantle components. Iron stable isotopes may therefore provide a powerful new means of fingerprinting mineralogical variations within the Earth's mantle and identifying the mineralogy of depleted and enriched components within the source regions of volcanic rocks

Readability, presentation and quality of allergy-related patient information leaflets: a cross sectional and longitudinal study

Objective: Patient information leaflets (PILs) are widely used to reinforce or illustrate health information and to complement verbal consultation. The objectives of the study were to assess the readability and presentation of PILs published by Allergy UK, and to conduct a longitudinal assessment to evaluate the impact of leaflet amendment and revision on readability. Methods: Readability of Allergy UK leaflets available in 2013 was assessed using Simple Measure of Gobbledegook (SMOG) and Flesch-Kincaid Reading Grade Formula. Leaflet presentation was evaluated using the Clear Print Guidelines of the Royal National Institute of Blind People (RNIB) and the Patient Information Appraisal System developed by the British Medical Association (BMA). Changes in the leaflets’ readability scores over five years were investigated. Results: 108 leaflets, covering a wide range of allergic conditions and treatment options, were assessed. The leaflets had average SMOG and Flesch-Kincaid scores of 13.9 (range 11-18, SD 1.2) and 10.9 (range 5-17, SD 2.1) respectively. All leaflets met the RNIB Clear Print guidelines, with the exception of font size which was universally inadequate. The leaflets scored on average 10 (median 10, range 7-15) out of a maximum of 27 on the BMA checklist. The overall average SMOG score of 31 leaflets available in both 2008 and 2013 had not changed significantly. The process of leaflet revision resulted in 1% change in readability scores overall, with a predominantly upward trend with six leaflets increasing their readability score by >10% and only three decreasing by >10%. Conclusion: Allergy-related patient information leaflets are well presented but have readability levels that are higher than those recommended for health information. Involving service users in the process of leaflet design, together with systematic pre-publication screening of readability would enhance the accessibility and comprehensibility of written information for people with allergy and their careers

Team gender diversity : the effects of gender, type of team and organisational context.

This thesis examines the effect of team gender diversity on team functioning. Whilst both theoretically and empirically there is considerable support for the proposition that gender diversity will affect team functioning, past research does not provide a coherent body of observed findings. Reviewing the literature does however suggest the possibility that the conflicting pattern of findings might be due to several contingency factors. This thesis therefore also explored the possibility of differential effects across gender, type of team and organisational context. Cross-sectional questionnaire based studies were conducted in three very different organisational contexts: a male dominated manufacturing industry, a female dominated health service, and a gender balanced local government housing department. Taken in combination the results of the three studies provided strong support for the proposition that gender diversity is associated with perceptions of team functioning. However, the relationship was not found to be straightforward. Firstly, a differential effect of team gender diversity on men and women was found. Secondly, it was shown that the effects of team gender diversity were greater within management than non-management teams. Finally, although gender diversity was found to affect perceptions of team functioning within all three studies, the nature and magnitude of the effects was found to be dependant upon the organisational context. Within gender skewed contexts (i.e. male dominated or female dominated contexts) a token representation of the minority was found to be particularly detrimental to perceptions of team functioning. However, once the proportion of women in the team exceeded tokenism, greater gender diversity was found to be beneficial to the team. In contrast, in the gender balanced context diversity per se was not found to effect team functioning, rather the presence of women in particular created better team functioning

Development and validation of a protocol to identify and recruit participants into a large scale study on liver fluke in cattle

Abstract Background Liver fluke infection caused by the parasite Fasciola hepatica is a major cause of production losses to the cattle industry in the UK. To investigate farm-level risk factors for fluke infection, a randomised method to recruit an appropriate number of herds from a defined geographical area into the study was required. The approach and hurdles that were encountered in designing and implementing this study are described. The county of Shropshire, England, was selected for the study because of the variation between farms in exposure to fluke infection observed in an earlier study. Results From a sampling list of 569 holdings in Shropshire randomly drawn from the RADAR cattle population dataset, 396 (69.6%) holdings were successfully contacted by telephone and asked if they would be interested in taking part in the study. Of 296 farmers who agreed to receive information packs by post, 195 (65.9%) agreed to take part in the study. Over the period October 2014 – April 2015 visits were made to 100 dairy and 95 non-dairy herds. During the farm visits 40 faecal samples +/− bulk-tank milk samples were collected and a questionnaire administered. Composite faecal samples were analysed for the presence of F. hepatica eggs by sedimentation and bulk tank milk samples were tested with an antibody ELISA for F. hepatica. Forty-five (49%) of non-dairy herds were positive for liver fluke infection as determined by the finding of one or more fluke eggs, while 36 (36%) dairy herds had fluke positive faecal samples and 41 (41%) dairy herds were positive for F. hepatica antibody. Eighty-seven (45.8%) farmers said that they monitored their cattle for liver fluke infection and 118 (62.1%) reported that they used flukicide drugs in their cattle. Conclusions Using a protocol of contacting farmers directly by telephone and subsequently sending information by post, 79% of the target sample size was successfully recruited into the study. A dataset of farm-specific information on possible risk factors for liver fluke infection and corresponding liver-fluke infection status was generated for the development of statistical models to identify risk factors for liver fluke infection at the farm-level

Promoting writing amongst peers: establishing a community of writing practice for early career academics

In the current research-focused climate, academics are facing increasing pressure to produce research outputs. This pressure can prove particularly daunting for early career (EC) academics, who are simultaneously attempting to master new teaching and administrative demands while establishing their own independent research trajectories. Previous reports suggest that academic writing retreats can be an effective way of increasing research outputs. Such retreats generally involve academics from a range of career stages and require expert facilitators. Through organising a series of structured writing events, this project aims to cultivate an enduring community of practice for academic writers. Reflecting on our EC retreat and subsequent writing days with academics from different career stages, we suggest that success hinged on three key factors: (1) A formal structure comprising bounded periods of intense writing, flanked by group reviewing and goal-setting; (2) Co-located writing with participants based in a shared space, away from their usual workstation and distractions; (3) Peer discussions involving participants at a similar career stage. Specifically we found that writing amongst ‘equals’ increased productivity and confidence amongst EC academics

Epidemiology of dengue in a high-income country: a case study in Queensland, Australia

Background: Australia is one of the few high-income countries where dengue transmission regularly occurs. Dengue is a major health threat in North Queensland (NQ), where the vector Aedes aegypti is present. Whether NQ should be considered as a dengue endemic or epidemic region is an ongoing debate. To help address this issue, we analysed the characteristics of locally-acquired (LA) and imported dengue cases in NQ through time and space. We describe the epidemiology of dengue in NQ from 1995 to 2011, to identify areas to target interventions. We also investigated the timeliness of notification and identified high-risk areas. Methods: Data sets of notified cases and viraemic arrivals from overseas were analysed. We developed a time series based on the LA cases and performed an analysis to capture the relationship between incidence rate and demographic factors. Spatial analysis was used to visualise incidence rates through space and time. Results: Between 1995 and 2011, 93.9% of reported dengue cases were LA, mainly in the 'Cairns and Hinterland' district; 49.7% were males, and the mean age was 38.0 years old. The sources of imported cases (6.1%) were Indonesia (24.6%), Papua New Guinea (23.2%), Thailand (13.4%), East Timor (8.9%) and the Philippines (6.7%), consistent with national data. Travellers importing dengue were predominantly in the age groups 30-34 and 45-49 years old, whereas the age range of patients who acquired dengue locally was larger. The number of LA cases correlated with the number of viraemic importations. Duration of viraemia of public health importance was positively correlated with the delay in notification. Dengue incidence varied over the year and was typically highest in summer and autumn. However, dengue activity has been reported in winter, and a number of outbreaks resulted in transmission year-round. Conclusions: This study emphasizes the importance of delay in notification and consequent duration of viraemia of public health importance for dengue outbreak duration. It also highlights the need for targeted vector control programmes and surveillance of travellers at airports as well as regularly affected local areas. Given the likely increase in dengue transmission with climate change, endemicity in NQ may become a very real possibility

Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions

Cutaneous Nod2 expression regulates the skin microbiome and wound healing in a murine model

The skin microbiome exists in dynamic equilibrium with the host but when the skin is compromised, bacteria can colonise the wound and impair wound healing. Thus the interplay between normal skin-microbial interactions versus pathogenic-microbial interactions in wound repair is important. Bacteria are recognised by innate host pattern recognition receptors (PRRs) and we previously demonstrated an important role for the PRR NOD2 (nucleotide-binding oligomerisation domains-containing protein 2) in skin wound repair. NOD2 is implicated in changes in the composition of the intestinal microbiota in Crohn’s disease but its role on skin microbiota is unknown. Nod2-deficient (Nod2-/-) mice had an inherently altered skin microbiome compared with wild-type (WT) controls. Furthermore, we found Nod2-/- skin microbiome dominated and caused impaired healing, revealed in cross-fostering experiments of WT with Nod2-/- pups which then acquired altered cutaneous bacteria and delayed healing. High-throughput sequencing and qPCR revealed a significant compositional shift, specifically in the genus Pseudomonas in Nod2-/- mice. To confirm whether Pseudomonas directly impairs wound healing, WT mice were infected with P. aeruginosa biofilms and akin to Nod2-/- mice, were found to exhibit a significant delay in wound repair. Collectively, these studies demonstrate the importance of the microbial communities in skin wound healing outcome

Therapeutic equivalence study of two formulations (innovator v. generic) of beclomethasone dipropionate in adult asthmatic patients

Objective. To study the therapeutic equivalence of two formulations (innovator v. generic) of beclomethasone dipropionate (BDP) 400 pg twice daily administered per metered dose inhaler (MDO, in adults with moderate to severe asthma.Methods. A double-blind randomised parallel-group trial was performed with a 2-week run-in and an 8-week treatment period. Thirty-six symptomatic adult asthmatics on a mean daily dose of 750 μg inhaled corticosteroids during run-in, a mean forced expiratory volume in 1 second (FEV1) of 70% predicted normal and a mean histamine concentration provoking a 20% reduction in FEV1 (histamine PC20 of 0.11 mg/l were randomised to one of the two treatment groups. Primary variables were morning peak expiratory flow (mPEF), FEV1 and histamine PC20- Secondary variables were β2-agonist use, symptom score and nocturnal awakening. The Schuirmann two one-sided tests procedure was used for the statistical analysis. Ninety-five per cent confidence intervals (CIs) were calculated for the differences in means.Results. The mean differences end of treatment to baseline for the two formulations (Becotide and Beclate) respectively were: mPEF 5.61/min (0 -16.4- 27.6) and -22.31/min (0 -35.6 - -9); FEV 1 -2.90/0 (0 -11 - 5.2) and 0.2% (0 -4.8 -5.2); Histamine PC20-0.04 mg/ml (0 -0.15- 0.06) and 0.02 mg/ mi (0 -0.37 - 0.4). Changes in clinical variables were not conclusive. The mean differences with CIs for Primary variables were contained within the limits set for equivalence. The sample size was sufficient to differentiate the groups for mPEF, but this was not of clinical significance.Conclusion. After 8 weeks of treatment the two formulations of BDP, delivered by MDI through a large-volume spacer, were therapeutically equivalent in moderate-to-severe asthmatic adults