Phylogenetic and phenotypic divergence of an insular radiation of birds

Evolutionary divergence of lineages is one of the key mechanisms underpinning large scale patterns in biogeography and biodiversity. Island systems have been highly influential in shaping theories of evolutionary diversification and here I use the insular Zosteropidae of the south west Pacific to investigate the roles of ecology and biogeography in promoting evolutionary divergence. Initially I build a phylogenetic tree of the study group and use it to reveal the pattern of colonisation and diversification. My results suggest a complex history of dispersal with the observed pattern most likely a result of repeated bouts of colonisation and extinction. I then use the new phylogeny to quantify the diversification rates of the Zosteropidae. I find a very high rate of lineage divergence and suggest the most likely explanation relates to extensive niche availability in the south west Pacific. I also find evidence for an overall slowdown in diversification combined with repeated bursts of accelerated speciation, consistent with a model of taxon cycles. I do not find evidence for sympatric speciation, however. Finally I combine morphological and phylogenetic data to investigate the mode of evolution, evidence for character displacement and influence of biogeography on trait evolution. I find little support for the traditional theory of character displacement in sympatric species. I do, however, find some support for biogeographic theories. Taken together my results do not support traditional theories on the ecological and biogeographical basis of divergence, even in those cases where Zosterops have been used as exemplars. This appears to be because those theories assume rather simple patterns of colonisation and a static ecological system. Instead, my results suggest that evolutionary diversification is dominated by recurrent waves of colonisation and extinction, which, viewed at any particular moment, tend to obscure any underlying ecological rules

Fluid-structure interaction simulation of the brachial artery undergoing flow-mediated dilation

Flow-mediated dilation (FMD) permits a non-invasive clinical assessment of endothelial dysfunction, a key indication of early atherosclerosis and cardiovascular diseases. This has significant implications with paediatric patients. FMD necessitates the measurement of brachial artery dilation from transient hyperaemia following a period of temporary ischemic occlusion. In addition to arterial diameter changes, the wall shear stress, blood pressure, and wall stiffness vary transiently in FMD, making it a complex fluid-structure interaction (FSI) problem. This work seeks to model the haemodynamic mechanisms associated with FMD utilising the open- source OpenFOAM-extend library1. Prior studies have demonstrated the suitability of this library for cardiovascular simulations2. Two FSI solvers, based on strong and weak coupling, were implemented for comparison. Both solvers utilise a partitioned approach, where the fluid and structure are solved separately and the information in each domain is exchanged at the FSI interface for each timestep. This is achieved using a dynamic mesh solver based on a discretisation of Laplace’s equation. The fluid flow solution is based on the finite volume method (FVM) and the displacement of the solid domain is solved by a Lagrangian FVM solver. The artery wall was modelled as a straight tube with physiological values for the internal diameter, density, wall thickness, Young’s modulus, and Poisson’s ratio3. A Newtonian incompressible fluid was assumed with physiological density and viscosity4. The inlet velocity for the fluid domain is specified from an in-vivo hyperaemic condition5. The simulation results demonstrate an important variation in the diameter of the arterial vessel during FMD, while haemodynamic wall shear stress and pressure values are also ascertained. These preliminary results are useful for comparing the implementation of strong and weak FSI solvers and for correlating arterial wall displacement with the prescribed in-vivo inlet velocity. Future work will focus on FMD in idealised and patient-specific bifurcation models where ischemic occlusion will be prescribed for the distal branching arteries

Multi-parameter computational model of flow mediated dilation with fluid-structure interaction coupled with lumped parameter approaches

Flow-mediated dilation (FMD) is a valuable non-invasive clinical assessment of endothelial dysfunction, a key indicator of atherosclerosis. The progression of atherosclerosis from paediatric ages can lead to the manifestation of cardiovascular diseases (CVDs) in later life. Hence, early lesion detection in younger years using FMD will heavily support timely disease assessment and treatment. In FMD, the diameter of the brachial artery is measured ultrasonically before, during, and after the inflation of a cuff applied to the lower arm of a subject. The cuff is placed distal to the ultrasound probe to capture predominantly endothelium-dependent vasodilation [1].The process induces a period of reactive hyperaemia, causing the brachial artery to vasodilate, due to an increase in shear stress that results in release of nitric oxide. The brachial artery ‘speak dilation is used for calculating the percentage difference between peak and baseline diameter (FMD percentage).Modelling FMD computationally offers a non-invasive assessment of vascular health and haemodynamic parameters

An improved process for the fabrication and surface treatment of custom-made titanium cranioplasty implants informed by surface analysis

Cranioplasty implants are routinely fabricated from commercially pure titanium plates by maxillofacial prosthetists. The differing fabrication protocols adopted by prosthetists working at different hospital sites gives rise to considerable variations in surface topography and composition of cranioplasty implants, with residues from the fabrication processes having been found to become incorporated into the surface of the implant. There is a growing recognition among maxillofacial prosthetists of the need to standardise these protocols to ensure quality and consistency of practice within the profession. In an effort to identify and eliminate the source of the inclusions associated with one such fabrication protocol, the present study examined the surfaces of samples subjected to each of the manufacturing steps involved. Surface and elemental analysis techniques identified the main constituent of the surface inclusions to be silicon from the glass beads used to texture the surface of the implant during fabrication. Subsequent analysis of samples prepared according to a revised protocol resulted in a more homogeneous titanium dioxide surface as evidenced by the reduction in area occupied by surface inclusions (from 8.51% ± 2.60% to 0.93% ± 0.62%). These findings may inform the development of improved protocols for the fabrication of titanium cranioplasty plates

Stable isotopes reveal the importance of seabirds and marine foods in the diet of St Kilda field mice

Introduced mammals have devastated island nesting seabird populations worldwide. Declines in breeding seabirds on St Kilda, UK, have been linked to climate change and predation from great skuas Stercorarius skuas, but the introduced St Kilda field mouse Apodemus sylvaticus hirtensis may also play a role by feeding on adults, chicks or eggs. Here, we use stable isotopes in St Kilda mouse blood and potential dietary items to investigate their foraging ecology, specifically focussing on the importance of seabirds and marine foods in their diet. Mice were seasonally sampled at three sites on Hirta, St Kilda over three consecutive years (2010–2012). The δ13C and δ15N ratios were used in analyses, including isotope niche and dietary source mixing models, to examine foraging behaviour among locations and between seabird breeding seasons. Mice sampled in Carn Mor – where the majority of the island’s seabirds nest - had consistently higher δ13C than other locations throughout the year, with δ15N also being significantly higher for all but one comparison. The isotopic niche width (SEAs) of Carn Mor mice in each season were distinct from the other locations, and became smaller during the seabird breeding season. Dietary mixing models revealed that seabirds made up a large proportion of the diet for mice from Carn Mor, particularly during the seabird breeding season. In conclusion, our work reveals that seabird-derived foods are likely to form a significant part of the diet of St Kilda mice populations located in and around breeding colonies. It is unclear however, whether this is from scavenging or predation of seabirds, or through their discarded food items. Given that mice have had significant effects on seabird populations elsewhere, it is important to carry out further work to determine whether mice are a significant cause of seabird mortality in this island ecosystem

Learning to prescribe - pharmacists' experiences of supplementary prescribing training in England

Background: The introduction of non-medical prescribing for professions such as pharmacy and nursing in recent years offers additional responsibilities and opportunities but attendant training issues. In the UK and in contrast to some international models, becoming a non-medical prescriber involves the completion of an accredited training course offered by many higher education institutions, where the skills and knowledge necessary for prescribing are learnt. Aims: to explore pharmacists' perceptions and experiences of learning to prescribe on supplementary prescribing (SP) courses, particularly in relation to inter-professional learning, course content and subsequent use of prescribing in practice. Methods: A postal questionnaire survey was sent to all 808 SP registered pharmacists in England in April 2007, exploring demographic, training, prescribing, safety culture and general perceptions of SP. Results: After one follow-up, 411 (51%) of pharmacists responded. 82% agreed SP training was useful, 58% agreed courses provided appropriate knowledge and 62% agreed that the necessary prescribing skills were gained. Clinical examination, consultation skills training and practical experience with doctors were valued highly; pharmacology training and some aspects of course delivery were criticised. Mixed views on inter-professional learning were reported – insights into other professions being valued but knowledge and skills differences considered problematic. 67% believed SP and recent independent prescribing (IP) should be taught together, with more diagnostic training wanted; few pharmacists trained in IP, but many were training or intending to train. There was no association between pharmacists' attitudes towards prescribing training and when they undertook training between 2004 and 2007 but earlier cohorts were more likely to be using supplementary prescribing in practice. Conclusion: Pharmacists appeared to value their SP training and suggested improvements that could inform future courses. The benefits of inter-professional learning, however, may conflict with providing professionspecific training. SP training may be perceived to be an instrumental 'stepping stone' in pharmacists' professional project of gaining full IP status

Improved Segmentation of the Intracranial and Ventricular Volumes in Populations with Cerebrovascular Lesions and Atrophy Using 3D CNNs

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N = 528 subjects for ICV, N = 501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with vascular cognitive impairment and high white matter hyperintensity burden. Two of the three test sets came from studies not used in the training dataset. We assessed our algorithms relative to four state-of-the-art ICV extraction methods (MONSTR, BET, Deep Extraction, FreeSurfer, DeepMedic), as well as two ventricular segmentation tools (FreeSurfer, DeepMedic). Our multi-contrast models outperformed other methods across many of the evaluation metrics, with average Dice coefficients of 0.98 and 0.96 for ICV and ventricular segmentation respectively. Both models were also the most time efficient, segmenting the structures in orders of magnitude faster than some of the other available methods. Our networks showed an increased accuracy with the use of a conditional random field (CRF) as a post-processing step. We further validated both segmentation models, highlighting their robustness to images with lower resolution and signal-to-noise ratio, compared to tested techniques. The pipeline and models are available at: https://icvmapp3r.readthedocs.io and https://ventmapp3r.readthedocs.io to enable further investigation of the roles of ICV and ventricles in relation to normal aging and neurodegeneration in large multi-site studies

Rasch analyses of the Quick Inventory of Depressive Symptomatology Self-Report in neurodegenerative and major depressive disorders

BackgroundSymptoms of depression are present in neurodegenerative disorders (ND). It is important that depression-related symptoms be adequately screened and monitored in persons living with ND. The Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) is a widely-used self-report measure to assess and monitor depressive severity across different patient populations. However, the measurement properties of the QIDS-SR have not been assessed in ND.AimTo use Rasch Measurement Theory to assess the measurement properties of the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) in ND and in comparison to major depressive disorder (MDD).MethodsDe-identified data from the Ontario Neurodegenerative Disease Research Initiative (NCT04104373) and Canadian Biomarker Integration Network in Depression (NCT01655706) were used in the analyses. Five hundred and twenty participants with ND (Alzheimer’s disease or mild cognitive impairment, amyotrophic lateral sclerosis, cerebrovascular disease, frontotemporal dementia and Parkinson’s disease) and 117 participants with major depressive disorder (MDD) were administered the QIDS-SR. Rasch Measurement Theory was used to assess measurement properties of the QIDS-SR, including unidimensionality and item-level fit, category ordering, item targeting, person separation index and reliability and differential item functioning.ResultsThe QIDS-SR fit well to the Rasch model in ND and MDD, including unidimensionality, satisfactory category ordering and goodness-of-fit. Item-person measures (Wright maps) showed gaps in item difficulties, suggesting poor precision for persons falling between those severity levels. Differences between mean person and item measures in the ND cohort logits suggest that QIDS-SR items target more severe depression than experienced by the ND cohort. Some items showed differential item functioning between cohorts.ConclusionThe present study supports the use of the QIDS-SR in MDD and suggest that the QIDS-SR can be also used to screen for depressive symptoms in persons with ND. However, gaps in item targeting were noted that suggests that the QIDS-SR cannot differentiate participants falling within certain severity levels. Future studies would benefit from examination in a more severely depressed ND cohort, including those with diagnosed clinical depression

Common Data Elements to Facilitate Sharing and Re-use of Participant-Level Data: Assessment of Psychiatric Comorbidity Across Brain Disorders

The Ontario Brain Institute\u27s “Brain-CODE” is a large-scale informatics platform designed to support the collection, storage and integration of diverse types of data across several brain disorders as a means to understand underlying causes of brain dysfunction and developing novel approaches to treatment. By providing access to aggregated datasets on participants with and without different brain disorders, Brain-CODE will facilitate analyses both within and across diseases and cover multiple brain disorders and a wide array of data, including clinical, neuroimaging, and molecular. To help achieve these goals, consensus methodology was used to identify a set of core demographic and clinical variables that should be routinely collected across all participating programs. Establishment of Common Data Elements within Brain-CODE is critical to enable a high degree of consistency in data collection across studies and thus optimize the ability of investigators to analyze pooled participant-level data within and across brain disorders. Results are also presented using selected common data elements pooled across three studies to better understand psychiatric comorbidity in neurological disease (Alzheimer\u27s disease/amnesic mild cognitive impairment, amyotrophic lateral sclerosis, cerebrovascular disease, frontotemporal dementia, and Parkinson\u27s disease)

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death : Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee

BACKGROUND: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. METHODS: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015). RESULTS: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. CONCLUSIONS: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials