Mediation of the total effect of cystic fibrosis‐related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study

Abstract: Aim: To investigate whether the effect of cystic fibrosis‐related diabetes (CFRD) on the composite outcome of mortality or transplant could act through lung function, pulmonary exacerbations and/or nutritional status. Methods: A retrospective cohort of adult cystic fibrosis (CF) patients who had not been diagnosed with CFRD were identified from the UK Cystic Fibrosis Registry (n = 2750). Rate of death or transplant was compared between patients who did and did not develop CFRD (with insulin use) during follow‐up using Poisson regression, separately by sex. Causal mediation methods were used to investigate whether lung function, pulmonary exacerbations and nutritional status lie on the causal pathway between insulin‐treated CFRD and mortality/transplant. Results: At all ages, the mortality/transplant rate was higher in both men and women diagnosed with CFRD. Pulmonary exacerbations were the strongest mediator of the effect of CFRD on mortality/transplant, with an estimated 15% [95% CI: 7%, 28%] of the effect at 2 years post‐CFRD diagnosis attributed to exacerbations, growing to 24% [95% CI: 9%, 46%] at 4 years post‐diagnosis. Neither lung function nor nutritional status were found to be significant mediators of this effect. Estimates were similar but with wider confidence intervals in a cohort that additionally included people with CFRD but not using insulin. Conclusion: There is evidence that pulmonary exacerbations mediate the effect of CFRD on mortality but, as they are estimated to mediate less than one‐quarter of the total effect, the mechanism through which CFRD influences survival may involve other factors

Patterns of space use in sympatric marine colonial predators reveals scales of spatial partitioning

E.L.J. and D.J.F.R. were funded under Scottish Government grant MMSS001/01. D.J.F.R. was funded by the UK Department of Energy and Climate Change (DECC) as part of their Offshore Energy Strategic Environmental Assessment programme. S.S. was part-funded by the EU MYFISH project.Species distribution maps can provide important information to focus conservation efforts and enable spatial management of human activities. Two sympatric marine predators, grey seals Halichoerus grypus and harbour seals Phoca vitulina have overlapping ranges on land and at sea but contrasting population dynamics around Britain: whilst grey seals have generally increased, harbour seals have shown significant regional declines. We analysed two decades of at-sea movement data and terrestrial count data from these species to produce high resolution, broad-scale maps of distribution and associated uncertainty to inform conservation and management. Our results showed that grey seals use offshore areas connected to their haul-out sites by prominent corridors and harbour seals primarily stay within 50km of the coastline. Both species show fine-scale offshore spatial segregation off the east coast of Britain and broad-scale partitioning off western Scotland. These results illustrate that for broad-scale marine spatial planning, the conservation needs of harbour seals (primarily inshore, the exception being selected offshore usage areas) are different from those of grey seals (up to 100km offshore and corridors connecting these areas to haul-out sites). More generally, our results illustrate the importance of detailed knowledge of marine predator distributions to inform marine spatial planning; for instance, spatial prioritisation is not necessarily the most effective spatial planning strategy even when conserving species with similar taxonomy.Peer reviewe

Analytics in online and offline language learning environments: the role of learning design to understand student online engagement

Language education has a rich history of research and scholarship focusing on the effectiveness of learning activities and the impact these have on student behaviour and outcomes. One of the basic assumptions in foreign language pedagogy and CALL in particular is that learners want to be able to communicate effectively with native speakers of their chosen language. Combining principles of learning analytics and Big Data with learning design, this study used a student activity based taxonomy adopted by the Open University UK to inform module design. The learning designs of four introductory and intermediary language education modules and online engagement of 2111 learners were contrasted using weekly learning design data. In this study, we aimed to explore how learning design decisions made by language teachers influenced students’ engagement in the VLE. Using fixed effect models, our findings indicated that 55% of variance of weekly online engagement in these four modules was explained by the way language teachers designed weekly learning design activities. Our learning analytics study highlights the potential affordances for CALL researchers to use the power of learning design and big data to explore and understand the complexities and dynamics of language learning for students and teachers

Spatial Variation in Foraging Behaviour of a Marine Top Predator (Phoca vitulina) Determined by a Large-Scale Satellite Tagging Program

The harbour seal (Phoca vitulina) is a widespread marine predator in Northern Hemisphere waters. British populations have been subject to rapid declines in recent years. Food supply or inter-specific competition may be implicated but basic ecological data are lacking and there are few studies of harbour seal foraging distribution and habits. In this study, satellite tagging conducted at the major seal haul outs around the British Isles showed both that seal movements were highly variable among individuals and that foraging strategy appears to be specialized within particular regions. We investigated whether these apparent differences could be explained by individual level factors: by modelling measures of trip duration and distance travelled as a function of size, sex and body condition. However, these were not found to be good predictors of foraging trip duration or distance, which instead was best predicted by tagging region, time of year and inter-trip duration. Therefore, we propose that local habitat conditions and the constraints they impose are the major determinants of foraging movements. Specifically the distance to profitable feeding grounds from suitable haul-out locations may dictate foraging strategy and behaviour. Accounting for proximity to productive foraging resources is likely to be an important component of understanding population processes. Despite more extensive offshore movements than expected, there was also marked fidelity to the local haul-out region with limited connectivity between study regions. These empirical observations of regional exchange at short time scales demonstrates the value of large scale electronic tagging programs for robust characterization of at-sea foraging behaviour at a wide spatial scale

Relationship of trip distance and duration by sex for each region.

<p>Plots of distance travelled per trip against trip duration shown for each region. Pink circles show data from female seals and blue circles show males. Lines are LOESS smoothers (span = 1) which were added to highlight trends. Apparent is the large degree of variability within region particularly for relatively long trip durations. Note that the horizontal axis varies among plots, also highlighting the differences in the range of trips among regions.</p

Tag deployment distribution and longevity.

<p>Individual tag deployments by site. The length of each line shows the duration of deployment for an individual seal.</p

Difference in trip duration, distance and maximum depth by sex.

<p>Box-plot representation of distributions of trip-duration, distance-travelled-per-trip and maximum dive depth within a trip between the sexes. Considerable overlap is displayed between the sexes. While in some populations male seals consistently appeared to travel further, sex did not turn out to be a good predictor of trip-duration or distance travelled in general.</p

118 smoothed telemetry tracks and capture locations.

<p>Smoothed and interpolated tracks of all 118 seals, males in shades of blue, females in shades of red. Green circles show where animals were captured and the major divisions of the data into regions are shown as labelled boxes. ETOPO-2 bathymetry data (ETOPO-2USDC, 2006) in meters are shown.</p

Experimental observation of spin delocalisation onto the aryl-alkynyl ligand in the complexes [Mo(CCAr)(Ph2PCH2CH 2PPh2)(η-C7H7)]+ (Ar = C6H5, C6H4-4-F; C 7H7 = cycloheptatrienyl): An EPR and ENDOR investigation

The paramagnetic aryl-alkynyl complexes [Mo(CCAr)(dppe)(η-C7H7)]+ (dppe = Ph2PCH2CH2PPh2; Ar = C6H5, [1]+; C6D5, [2]+; C6H4-4-F, [3]+; C6H4-4-Me, [5]+) and [Mo(CCBut)(dppe)(η-C7H7)]+ [4]+, have been investigated in a combined EPR and ENDOR study. Direct experimental evidence for the delocalisation of unpaired spin density over the framework of an aryl-alkynyl ligand has been obtained. The X-band solution EPR spectrum of the 4-fluoro derivative, [3]+, exhibits resolved hyperfine coupling to the remote para position of the aryl group [aiso(19F) = 4.5 MHz, (1.6 G)] in addition to couplings attributable to 95/97Mo, 31P and 1H of the C7H7 ring. A full analysis of the 1H ENDOR spectra is restricted by the low g anisotropy of the system which prevents the use of orientation selection. However, inter-comparison of the 1H cw-ENDOR frozen solution spectra of [1]+, [2]+, [4]+ and [5]+, combined with spectral simulation informed by calculated values derived from DFT investigations, has facilitated estimation of the experimental aiso(1H) hyperfine couplings of [1]+ including the ortho, ±3.7 MHz (±1.3 G) and para, ±3.9 MHz (±1.4 G) positions of the C6H5 substituent of the aryl-alkynyl ligand