Diagnosis of multiple sclerosis: progress and challenges

The diagnosis of multiple sclerosis (MS) is based on typical neurological symptoms and signs along with evidence of dissemination of central nervous system (CNS) lesions in space and time. Magnetic resonance imaging (MRI) is often sufficient to confirm the diagnosis when characteristic lesions of MS accompany a typical clinical syndrome, but in some patients, further supportive information can be obtained from cerebrospinal fluid examination and neurophysiological testing. It is important to differentiate MS not only from other diseases in which demyelination is a feature e.g. neuromyelitis spectrum disorder (NMOSD) and acute disseminated encephalomyelitis (ADEM), but also non-demyelinating conditions such as chronic small vessel disease and other inflammatory, granulomatous, infective, metabolic and genetic causes that can mimic MS. Advances in MRI, serological and genetic tests have greatly helped in distinguishing MS from these conditions, but misdiagnosis can occur. In this review, we explore the progress and challenges in the diagnosis of MS with reference to diagnostic criteria, important differential diagnoses, current controversies and uncertainties, and future prospects

Geometric control of myogenic cell fate.

This work combines expertise in stem cell biology and bioengineering to define the system for geometric control of proliferation and differentiation of myogenic progenitor cells. We have created an artificial niche of myogenic progenitor cells, namely, modified extracellular matrix (ECM) substrates with spatially embedded growth or differentiation factors (GF, DF) that predictably direct muscle cell fate in a geometric pattern. Embedded GF and DF signal progenitor cells from specifically defined areas on the ECM successfully competed against culture media for myogenic cell fate determination at a clearly defined boundary. Differentiation of myoblasts into myotubes is induced in growth-promoting medium, myotube formation is delayed in differentiation-promoting medium, and myogenic cells, at different stages of proliferation and differentiation, can be induced to coexist adjacently in identical culture media. This method can be used to identify molecular interactions between cells in different stages of myogenic differentiation, which are likely to be important determinants of tissue repair. The designed ECM niches can be further developed into a vehicle for transplantation of myogenic progenitor cells maintaining their regenerative potential. Additionally, this work may also serve as a general model to engineer synthetic cellular niches to harness the regenerative potential of organ stem cells

Polynomial Interrupt Timed Automata

Interrupt Timed Automata (ITA) form a subclass of stopwatch automata where reachability and some variants of timed model checking are decidable even in presence of parameters. They are well suited to model and analyze real-time operating systems. Here we extend ITA with polynomial guards and updates, leading to the class of polynomial ITA (PolITA). We prove the decidability of the reachability and model checking of a timed version of CTL by an adaptation of the cylindrical decomposition method for the first-order theory of reals. Compared to previous approaches, our procedure handles parameters and clocks in a unified way. Moreover, we show that PolITA are incomparable with stopwatch automata. Finally additional features are introduced while preserving decidability

Mixture models for distance sampling detection functions

Funding: EPSRC DTGWe present a new class of models for the detection function in distance sampling surveys of wildlife populations, based on finite mixtures of simple parametric key functions such as the half-normal. The models share many of the features of the widely-used “key function plus series adjustment” (K+A) formulation: they are flexible, produce plausible shapes with a small number of parameters, allow incorporation of covariates in addition to distance and can be fitted using maximum likelihood. One important advantage over the K+A approach is that the mixtures are automatically monotonic non-increasing and non-negative, so constrained optimization is not required to ensure distance sampling assumptions are honoured. We compare the mixture formulation to the K+A approach using simulations to evaluate its applicability in a wide set of challenging situations. We also re-analyze four previously problematic real-world case studies. We find mixtures outperform K+A methods in many cases, particularly spiked line transect data (i.e., where detectability drops rapidly at small distances) and larger sample sizes. We recommend that current standard model selection methods for distance sampling detection functions are extended to include mixture models in the candidate set.Publisher PDFPeer reviewe

Subbarrel patterns in somatosensory cortical barrels can emerge from local dynamic instabilities

Complex spatial patterning, common in the brain as well as in other biological systems, can emerge as a result of dynamic interactions that occur locally within developing structures. In the rodent somatosensory cortex, groups of neurons called "barrels" correspond to individual whiskers on the contralateral face. Barrels themselves often contain subbarrels organized into one of a few characteristic patterns. Here we demonstrate that similar patterns can be simulated by means of local growth-promoting and growth-retarding interactions within the circular domains of single barrels. The model correctly predicts that larger barrels contain more spatially complex subbarrel patterns, suggesting that the development of barrels and of the patterns within them may be understood in terms of some relatively simple dynamic processes. We also simulate the full nonlinear equations to demonstrate the predictive value of our linear analysis. Finally, we show that the pattern formation is robust with respect to the geometry of the barrel by simulating patterns on a realistically shaped barrel domain. This work shows how simple pattern forming mechanisms can explain neural wiring both qualitatively and quantitatively even in complex and irregular domains. © 2009 Ermentrout et al

Parks Canada’s adaptation framework and workshop approach: Lessons learned across a diverse series of adaptation workshops

In 2017, the Canadian Parks Council Climate Change Working Group, a team of federal, provincial, and territorial representatives, developed a Climate Change Adaptation Framework for Parks and Protected Areas, guiding practitioners through a simple, effective five-step adaptation process. This framework was adapted by Parks Canada into a two-day adaptation workshop approach, with 11 workshops subsequently held from September 2017 to May 2019 at Parks Canada sites in the Yukon, Quebec, Manitoba, Alberta, Nova Scotia, British Columbia, Newfoundland, and Ontario. Lessons learned from each workshop have been integrated into the approach, with the development of tools and guidance for each phase of the process, and a shareable, visual “placemat” that describes each step of the framework, acting as a map for those navigating the process

A rare presentation of atypical demyelination: tumefactive multiple sclerosis causing Gerstmann's syndrome

r. KS has been supported by a Higher Education Funding Council for England (HEFCE) Clinical Senior Lectureshi

Cloning and expression of activation induced cytidine deaminase from Bos taurus'

Activation induced cytidine deaminase is an enzyme crucial to somatic hypermutation and gene conversion, processes that are essential for the diversification of Ig V genes. The bovine Ig repertoire appears to be diversified by mechanisms that are significantly different to those that operate in humans and mice. This study set out to test the hypothesis that differences in the organization, coding sequence, expression or genomic location of the bovine AICDA gene enables the encoded enzyme to catalyse the unusual Ig diversification mechanism seen in cattle as well as conventional antigen-driven mutation. Characterization of bovine AICDA excluded the first two possibilities. AICDA expression was detected in lymphoid tissues from neonatal and older cattle, but AICDA cDNA could not be detected in muscle tissue. The pattern of gene expression did not therefore differ from that in other vertebrates. The AICDA cDNA was cloned and expressed successfully in Escherichia coli generating a phenotype consistent with the mutating action of this deaminase. Using a whole genome radiation hybrid panel, bovine AICDA was mapped to a region of bovine chromosome 5 syntenic with the location of human AICDA on chromosome 12. We conclude that the unusual nature of Ig diversification in cattle is unlikely to be attributable to the structure, sequence, activity or genomic location of bovine AICDA

Sequential Effects in Judgements of Attractiveness: The Influences of Face Race and Sex

In perceptual decision-making, a person’s response on a given trial is influenced by their response on the immediately preceding trial. This sequential effect was initially demonstrated in psychophysical tasks, but has now been found in more complex, real-world judgements. The similarity of the current and previous stimuli determines the nature of the effect, with more similar items producing assimilation in judgements, while less similarity can cause a contrast effect. Previous research found assimilation in ratings of facial attractiveness, and here, we investigated whether this effect is influenced by the social categories of the faces presented. Over three experiments, participants rated the attractiveness of own- (White) and other-race (Chinese) faces of both sexes that appeared successively. Through blocking trials by race (Experiment 1), sex (Experiment 2), or both dimensions (Experiment 3), we could examine how sequential judgements were altered by the salience of different social categories in face sequences. For sequences that varied in sex alone, own-race faces showed significantly less opposite-sex assimilation (male and female faces perceived as dissimilar), while other-race faces showed equal assimilation for opposite- and same-sex sequences (male and female faces were not differentiated). For sequences that varied in race alone, categorisation by race resulted in no opposite-race assimilation for either sex of face (White and Chinese faces perceived as dissimilar). For sequences that varied in both race and sex, same-category assimilation was significantly greater than opposite-category. Our results suggest that the race of a face represents a superordinate category relative to sex. These findings demonstrate the importance of social categories when considering sequential judgements of faces, and also highlight a novel approach for investigating how multiple social dimensions interact during decision-making