Quantifying uncertainty in brain-predicted age using scalar-on-image quantile regression

Prediction of subject age from brain anatomical MRI has the potential to provide a sensitive summary of brain changes, indicative of different neurodegenerative diseases. However, existing studies typically neglect the uncertainty of these predictions. In this work we take into account this uncertainty by applying methods of functional data analysis. We propose a penalised func16 tional quantile regression model of age on brain structure with cognitively normal (CN) subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and use it to predict brain age in Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) subjects. Unlike the machine learning approaches available in the literature of brain age prediction, which provide only point predictions, the outcome of our model is a prediction interval for each subject

Genetic monitoring detects an overlooked cryptic species and reveals the diversity and distribution of three invasive Rattus congeners in South Africa

Background: South Africa's long and extensive trade activity has ensured ample opportunities for exotic species introduction. Whereas the rich biodiversity of endemic southern African fauna has been the focus of many studies, invasive vertebrates are generally overlooked despite potential impacts on biodiversity, health and agriculture. Genetic monitoring of commensal rodents in South Africa which uncovered the presence of Rattus tanezumi, a South-East Asian endemic not previously known to occur in Africa, provided the impetus for expanded studies on all invasive Rattus species present. Results: To this end, intensified sampling at 28 South African localities and at one site in Swaziland, identified 149 Rattus specimens. Cytochrome b gene sequencing revealed the presence of two R. tanezumi, seven R. rattus and five R. norvegicus haplotypes in south Africa. Phylogenetic results were consistent with a single, recent R. tanezumi introduction and indicated that R. norvegicus and R. rattus probably became established following at least two and three independent introductions, respectively. Intra- and inter-specific diversity was highest in informal human settlements, with all three species occurring at a single metropolitan township site. Rattus norvegicus and R. rattus each occurred sympatrically with R. tanezumi at one and five sites, respectively. Karyotyping of selected R. rattus and R. tanezumi individuals identified diploid numbers consistent with those reported previously for these cryptic species. Ordination of bioclimatic variables and MaxEnt ecological niche modelling confirmed that the bioclimatic niche occupied by R. tanezumi in south Africa was distinct from that occupied in its naturalised range in south-east Asia suggesting that factors other than climate may influence the distribution of this species. Conclusions: This study has highlighted the value of genetic typing for detecting cryptic invasive species, providing historical insights into introductions and for directing future sampling. The apparent ease with which a cryptic species can become established signals the need for broader implementation of genetic monitoring programmes. In addition to providing baseline data and potentially identifying high-risk introduction routes, the predictive power of ecological niche modelling is enhanced when species records are genetically verified

Differentiation of two South African otter species (Aonyx capensis and Lutra maculicollis) from spraint based on partial CytB primer sets

AbstractAccurate species identification based on visual cues can be challenging due to morphological similarities and the cryptic nature of certain species. Thus a more conclusive method of identification is required, namely DNA barcoding. This is the case regarding two South African otter species, Cape Clawless otter (Aonyx capensis) and the spotted necked otter (Lutra maculicollis). Due to the cryptic nature of these animals faecal samples, known as spraints, are the easiest way of confirming the presence of the animal in an area. In this study, we compared results obtained for universal and partial CytB primer sets on collected spraint and tissue control samples. Universal CytB primers revealed a low percentage of amplified otter species from faecal samples (species specific amplification success of 10.9%) whereas, the partial CytB primer set resulted in successful amplification of 45 out of 55 (82%) samples. We were thus able to positively differentiate between the two otter species using the partial CytB primer set developed in this study. The ability to accurately identify species using partial DNA will be beneficial in understanding numerous aspects of the behaviour and ecological importance of animals in their environment

Modelling the penumbra in computed tomography

Background: In computed tomography (CT), the spot geometry is one of the main sources of error in CT images. Since X-rays do not arise from a point source, artefacts are produced. In particular there is a penumbra effect, leading to poorly defined edges within a reconstructed volume. Penumbra models can be simulated given a fixed spot geometry and the known experimental setup. Objective: This paper proposes to use a penumbra model, derived from Beer’s law, both to confirm spot geometry from penumbra data, and to quantify blurring in the image. Methods: Two models for the spot geometry are considered; one consists of a single Gaussian spot, the other is a mixture model consisting of a Gaussian spot together with a larger uniform spot. Results: The model consisting of a single Gaussian spot has a poor fit at the boundary. The mixture model (which adds a larger uniform spot) exhibits a much improved fit. The parameters corresponding to the uniform spot are similar across all powers, and further experiments suggest that the uniform spot produces only soft X-rays of relatively low-energy. Conclusions: Thus, the precision of radiographs can be estimated from the penumbra effect in the image. The use of a thin copper filter reduces the size of the effective penumbra

Microglial Activation Correlates with Disease Progression and Upper Motor Neuron Clinical Symptoms in Amyotrophic Lateral Sclerosis

We evaluated clinicopathological correlates of upper motor neuron (UMN) damage in amyotrophic lateral sclerosis (ALS), and analyzed if the presence of the C9ORF72 repeat expansion was associated with alterations in microglial inflammatory activity.Microglial pathology was assessed by IHC with 2 different antibodies (CD68, Iba1), myelin loss by Kluver-Barrera staining and myelin basic protein (MBP) IHC, and axonal loss by neurofilament protein (TA51) IHC, performed on 59 autopsy cases of ALS including 9 cases with C9ORF72 repeat expansion.Microglial pathology as depicted by CD68 and Iba1 was significantly more extensive in the corticospinal tract (CST) of ALS cases with a rapid progression of disease. Cases with C9ORF72 repeat expansion showed more extensive microglial pathology in the medulla and motor cortex which persisted after adjusting for disease duration in a logistic regression model. Higher scores on the clinical UMN scale correlated with increasing microglial pathology in the cervical CST. TDP-43 pathology was more extensive in the motor cortex of cases with rapid progression of disease.This study demonstrates that microglial pathology in the CST of ALS correlates with disease progression and is linked to severity of UMN deficits

TDP-43 in the hypoglossal nucleus identifies amyotrophic lateral sclerosis in behavioral variant frontotemporal dementia

The hypoglossal nucleus was recently identified as a key brain region in which the presence of TDP-43 pathology could accurately discriminate TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis (ALS). The objective of the present study was to assess the hypoglossal nucleus in behavioral variant frontotemporal dementia (bvFTD), and determine whether TDP-43 in this region is associated with clinical ALS. Twenty-nine cases with neuropathological FTLD-TDP and clinical bvFTD that had not been previously assessed for hypoglossal TDP-43 pathology were included in this study. Of these 29 cases, 41% (n = 12) had a dual diagnosis of bvFTD-ALS at presentation, all 100% (n = 12) of which demonstrated hypoglossal TDP-43 pathology. Of the 59% (n = 17) cohort that presented with pure bvFTD, 35% (n = 6) were identified with hypoglossal TDP-43 pathology. Review of the case files of all pure bvFTD cases revealed evidence of possible or probable ALS in 5 of the 6 hypoglossal-positive cases (83%) towards the end of disease, and this was absent from all cases without such pathology. In conclusion, the present study validates grading the presence of TDP-43 in the hypoglossal nucleus for the pathological identification of bvFTD cases with clinical ALS, and extends this to include the identification of cases with possible ALS at end-stage

Experiencing transnationalism at home:open borders and the everyday narratives of non-migrants

The normative migration rights literature has engaged with the situated experience of migration to a very limited extent, with particularly little attention paid to non-migrants living in receiving localities. This article argues that exploring the non-elite narratives of non-migrants provides valuable insights for normative theorising about migration rights. The discussion is illustrated with a description of research undertaken within rural migration-receiving communities in England, which shows how the narratives of non-migrants shape the experience of migration at a micro-level. This article discusses the implications of this research for normative theory in order to demonstrate the value of this methodological approach