Neurodevelopmental brain reserve in behavioural variant Frontotemporal Dementia

Background: Behavioural variant Frontotemporal Dementia (bvFTD) is an early-onset dementia characterised by early anterior cingulate (AC) neuropathological insult. The AC exhibits high morphological heterogeneity, which may be classified according to the presence of a paracingulate sulcus (PCS), a tertiary sulcus that, when present, develops during the third gestational trimester and thereafter remains stable throughout life. Aim: This thesis examines the role of the PCS in bvFTD, focusing on its prevalence and disease-specific associations with age at onset (AAO), disease progression, and survival. Furthermore, it aims to explore the impact of PCS presence on cerebralstructural and functional connectivity. Results: Hemispheric PCS frequencies in both sporadic and genetic bvFTD were similar to those of healthy individuals. Presence of a right PCS was associated with a later AAO, an accelerated rate of disease progression and reduced survival following AAO in sporadic bvFTD. In genetic bvFTD, possession of a right PCS was associated with a later AAO in GRN but not C9orf72 or MAPT mutation carriers. In a sub-group of GRN mutation carriers accelerated early disease progression after AAO was observed in individuals possessing a right PCS. In healthy individuals, we identified an association between left PCS presence and altered structural and functional connectivity.Conclusion: Whilst PCS presence is not a risk factor for the development of bvFTD, this thesis provides evidence that right PCS presence modifies disease expression, progression, and survival in this disease. As such, within the reserve framework, right PCS presence represents the first proxy of brain reserve in frontotemporal dementia. These findings establish a novel association between intrauterine neurodevelopment and the expression of a neurodegenerative disease – an insight with potential implications for future clinical trials in bvFTD. Finally, this thesis describes a novel link between structure and function and provides a plausible explanation of how cognitive advantages associated with paracingulate sulcal presence may be mediated by a highly connected local functional network reliant on short association fibres

Sub-Sets of Cancer Stem Cells Differ Intrinsically in Their Patterns of Oxygen Metabolism

PMCID: PMC3640080This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Australian bat lyssavirus infection in two horses

In May 2013, the first cases of Australian bat lyssavirus infections in domestic animals were identified in Australia. Two horses (filly-H1 and gelding-H2) were infected with the Yellow-bellied sheathtail bat (YBST) variant of Australian bat lyssavirus (ABLV). The horses presented with neurological signs, pyrexia and progressing ataxia. Intra-cytoplasmic inclusion bodies (Negri bodies) were detected in some Purkinje neurons in haematoxylin and eosin (H&E) stained sections from the brain of one of the two infected horses (H2) by histological examination. A morphological diagnosis of sub-acute moderate non-suppurative, predominantly angiocentric, meningo-encephalomyelitis of viral aetiology was made. The presumptive diagnosis of ABLV infection was confirmed by the positive testing of the affected brain tissue from (H2) in a range of laboratory tests including fluorescent antibody test (FAT) and real-time PCR targeting the nucleocapsid (N) gene. Retrospective testing of the oral swab from (H1) in the real-time PCR also returned a positive result. The FAT and immunohistochemistry (IHC) revealed an abundance of ABLV antigen throughout the examined brain sections. ABLV was isolated from the brain (H2) and oral swab/saliva (H1) in the neuroblastoma cell line (MNA). Alignment of the genome sequence revealed a 97.7% identity with the YBST ABLV strain

Livestock Protection Tools for California Ranchers

Conflicts between livestock and predators are perhaps inevitable, especially on extensively managed rangelands This publication helps producers evaluate livestock lethal and non-lethal protection tools that may fit their site-specific needs

Rising to the challenges-Reflections on Future-oriented Technology Analysis

Drawing upon the presentations made at the fourth conference on Future-oriented Technology Analysis, this essay reflects on the implications of the current period of instability and discontinuity for the practice of FTA or foresight. In the past the demand environment for foresight on research and innovation policy favoured application to priority-setting and articulation of demand. New tendencies include a heightened search for breakthrough science and a focus on grand societal challenges. By their nature boundary-spanning, these make it less easy to locate FTA institutionally to achieve the necessary cross-cutting perspective. New institutions, methods and combinations of methods are noted. Dealing with disruptive transformations is seen as the key forward challenge for the practice of FTA. © 2012 Elsevier Inc

Addressing the speed-accuracy simulation trade-off for adaptive spiking neurons

The adaptive leaky integrate-and-fire (ALIF) model is fundamental within computational neuroscience and has been instrumental in studying our brains in silico. Due to the sequential nature of simulating these neural models, a commonly faced issue is the speed-accuracy trade-off: either accurately simulate a neuron using a small discretisation time-step (DT), which is slow, or more quickly simulate a neuron using a larger DT and incur a loss in simulation accuracy. Here we provide a solution to this dilemma, by algorithmically reinterpreting the ALIF model, reducing the sequential simulation complexity and permitting a more efficient parallelisation on GPUs. We computationally validate our implementation to obtain over a 50× training speedup using small DTs on synthetic benchmarks. We also obtained a comparable performance to the standard ALIF implementation on different supervised classification tasks - yet in a fraction of the training time. Lastly, we showcase how our model makes it possible to quickly and accurately fit real electrophysiological recordings of cortical neurons, where very fine sub-millisecond DTs are crucial for capturing exact spike timing

Detection of human papillomavirus in laryngeal squamous cell carcinoma: systematic review and meta-analysis

Background: Recent studies have reported a human papillomavirus (HPV) prevalence of 20% to 30% in laryngeal squamous cell carcinoma (LSCC), although clinical data on HPV involvement remain largely inconsistent, ascribed by some to differences in HPV detection methods or in geographic origin of the studies. Objective To perform a systematic review and formal meta-analysis of the literature reporting on HPV detection in LSCC. Methods Literature was searched from January 1964 until March 2015. The effect size was calculated as event rates (95% confidence interval [CI]), with homogeneity testing using Cochran's Q and I2 statistics. Meta-regression was used to test the impact of study-level covariates (HPV detection method, geographic origin) on effect size. Potential publication bias was estimated using funnel plot symmetry. Results One hundred seventy nine studies were eligible, comprising a sample size of 7,347 LSCCs from different geographic regions. Altogether, 1,830 (25%) cases tested HPV-positive considering all methods, with effect size of 0.269 (95% CI: 0.242 to 0.297; random-effects model). In meta-analysis stratified by the 1) HPV detection technique and 2) geographic study origin, the between-study heterogeneity was significant only for geographic origin (P = .0001). In meta-regression, the HPV detection method (P = .876) or geographic origin (P = .234) were not significant study-level covariates. Some evidence for publication bias was found only for studies from North America and those using non–polymerase chain reaction methods, with a marginal effect on adjusted point estimates for both. Conclusions Variability in HPV detection rates in LSCC is explained by geographic origin of study but not by HPV detection method. However, they were not significant study-level covariates in formal meta-regression

Addressing the speed-accuracy simulation trade-off for adaptive spiking neurons

The adaptive leaky integrate-and-fire (ALIF) model is fundamental within computational neuroscience and has been instrumental in studying our brains $\textit{in silico}$. Due to the sequential nature of simulating these neural models, a commonly faced issue is the speed-accuracy trade-off: either accurately simulate a neuron using a small discretisation time-step (DT), which is slow, or more quickly simulate a neuron using a larger DT and incur a loss in simulation accuracy. Here we provide a solution to this dilemma, by algorithmically reinterpreting the ALIF model, reducing the sequential simulation complexity and permitting a more efficient parallelisation on GPUs. We computationally validate our implementation to obtain over a $50\times$ training speedup using small DTs on synthetic benchmarks. We also obtained a comparable performance to the standard ALIF implementation on different supervised classification tasks - yet in a fraction of the training time. Lastly, we showcase how our model makes it possible to quickly and accurately fit real electrophysiological recordings of cortical neurons, where very fine sub-millisecond DTs are crucial for capturing exact spike timing.Comment: 15 pages, 5 figure

Connected clusters: landscaping study

This study presents evidence from five dynamic, city region-based climate innovation clusters. Here businesses, academics, communities and government work together to deliver low-carbon innovation. We believe this concentration of resources, expertise and initiative is our best chance of meeting the Paris climate targets while also reaping social and economic benefits that come with the development and delivery of cleantech solutions. Climate-KIC’s ConnectedClusters project is an alliance of five city regions – Birmingham, Edinburgh, Frankfurt, London and Valencia – committed to sharing, replicating and scaling what works in developing innovation ecosystems for delivering effective climate action. Between now and 2020, the project will work hard to accelerate and enable transformation of the places we live into clean, prosperous and thriving cities and regions by developing new collaborative approaches to technology, procurement, investment and training. ConnectedClusters will help inform a transition away from product and technology innovation in isolation, towards a systemic, regionally-embedded approach to climate innovation. Paris shows that for our continued prosperity, transformation on a scale never witnessed before is imperative. Only by working together can we achieve that change

Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector

The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the MAJORANA Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure