Computational convergence of the path integral for real dendritic morphologies

Neurons are characterised by a morphological structure unique amongst biological cells, the core of which is the dendritic tree. The vast number of dendritic geometries, combined with heterogeneous properties of the cell membrane, continue to challenge scientists in predicting neuronal input-output relationships, even in the case of sub-threshold dendritic currents. The Green’s function obtained for a given dendritic geometry provides this functional relationship for passive or quasi-active dendrites and can be constructed by a sum-over-trips approach based on a path integral formalism. In this paper, we introduce a number of efficient algorithms for realisation of the sum-over-trips framework and investigate the convergence of these algorithms on different dendritic geometries. We demonstrate that the convergence of the trip sampling methods strongly depends on dendritic morphology as well as the biophysical properties of the cell membrane. For real morphologies, the number of trips to guarantee a small convergence error might become very large and strongly affect computational efficiency. As an alternative, we introduce a highly-efficient matrix method which can be applied to arbitrary branching structures

Spatial and stochastic epidemics : theory, simulation and control

It is now widely acknowledged that spatial structure and hence the spatial position of host populations plays a vital role in the spread of infection. In this work I investigate an ensemble of techniques for understanding the stochastic dynamics of spatial and discrete epidemic processes, with especial consideration given to SIR disease dynamics for the Levins-type metapopulation. I present a toolbox of techniques for the modeller of spatial epidemics. The highlight results are a novel form of moment closure derived directly from a stochastic differential representation of the epidemic, a stochastic simulation algorithm that asymptotically in system size greatly out-performs existing simulation methods for the spatial epidemic and finally a method for tackling optimal vaccination scheduling problems for controlling the spread of an invasive pathogen

Meshless methods for shear-deformable beams and plates based on mixed weak forms

Thin structural theories such as the shear-deformable Timoshenko beam and Reissner-Mindlin plate theories have seen wide use throughout engineering practice to simulate the response of structures with planar dimensions far larger than their thickness dimension. Meshless methods have been applied to construct numerical methods to solve the shear deformable theories. Similarly to the finite element method, meshless methods must be carefully designed to overcome the well-known shear-locking problem. Many successful treatments of shear-locking in the finite element literature are constructed through the application of a mixed weak form. In the mixed weak form the shear stresses are treated as an independent variational quantity in addition to the usual displacement variables. We introduce a novel hybrid meshless-finite element formulation for the Timoshenko beam problem that converges to the stable first-order/zero-order finite element method in the local limit when using maximum entropy meshless basis functions. The resulting formulation is free from the effects shear-locking. We then consider the Reissner-Mindlin plate problem. The shear stresses can be identified as a vector field belonging to the Sobelov space with square integrable rotation, suggesting the use of rotated Raviart-Thomas-Nedelec elements of lowest-order for discretising the shear stress field. This novel formulation is again free from the effects of shear-locking. Finally we consider the construction of a generalised displacement method where the shear stresses are eliminated prior to the solution of the final linear system of equations. We implement an existing technique in the literature for the Stokes problem called the nodal volume averaging technique. To ensure stability we split the shear energy between a part calculated using the displacement variables and the mixed variables resulting in a stabilised weak form. The method then satisfies the stability conditions resulting in a formulation that is free from the effects of shear-locking.Open Acces

Social media in construction: an exploratory case study.

Social media are considered as powerful tools to inuence people as well as businesses in a short time span. Therefore, systematic use of social media in a business environment can bring greater benets in no time. However, there are opposing views and criticisms around social media implementation within businesses. Nevertheless, many businesses are now active in social media platforms as means of marketing, recruiting people, improving brand image and so on. Yet, there are issues in implementing social media in a business environment as it involves devising proper guidelines and protocols for its usage and effective communication to the employees of the organisation. This becomes more complicated in the case of construction industry as it is fragmented and the industry is distinctly different compared to other industries. Therefore, this paper presents an exploratory study of a construction organisation in term of its social media implementation and use. It mainly focuses on the types of social media platforms used for personal, business and career development purposes; usage policy of the organisation; level of integration with business goals; signi- cance of social media on various branches of business and barriers in implementation

Rapid simulation of spatial epidemics : a spectral method

Spatial structure and hence the spatial position of host populations plays a vital role in the spread of infection. In the majority of situations, it is only possible to predict the spatial spread of infection using simulation models, which can be computationally demanding especially for large population sizes. Here we develop an approximation method that vastly reduces this computational burden. We assume that the transmission rates between individuals or sub-populations are determined by a spatial transmission kernel. This kernel is assumed to be isotropic, such that the transmission rate is simply a function of the distance between susceptible and infectious individuals; as such this provides the ideal mechanism for modelling localised transmission in a spatial environment. We show that the spatial force of infection acting on all susceptibles can be represented as a spatial convolution between the transmission kernel and a spatially extended ‘image’ of the infection state. This representation allows the rapid calculation of stochastic rates of infection using fast-Fourier transform (FFT) routines, which greatly improves the computational efficiency of spatial simulations. We demonstrate the efficiency and accuracy of this fast spectral rate recalculation (FSR) method with two examples: an idealised scenario simulating an SIR-type epidemic outbreak amongst N habitats distributed across a two-dimensional plane; the spread of infection between US cattle farms, illustrating that the FSR method makes continental-scale outbreak forecasting feasible with desktop processing power. The latter model demonstrates which areas of the US are at consistently high risk for cattle-infections, although predictions of epidemic size are highly dependent on assumptions about the tail of the transmission kernel

Evaluating the performance of tools used to call minority variants from whole genome short-read data.

Background: High-throughput whole genome sequencing facilitates investigation of minority virus sub-populations from virus positive samples. Minority variants are useful in understanding within and between host diversity, population dynamics and can potentially assist in elucidating person-person transmission pathways. Several minority variant callers have been developed to describe low frequency sub-populations from whole genome sequence data. These callers differ based on bioinformatics and statistical methods used to discriminate sequencing errors from low-frequency variants. Methods: We evaluated the diagnostic performance and concordance between published minority variant callers used in identifying minority variants from whole-genome sequence data from virus samples. We used the ART-Illumina read simulation tool to generate three artificial short-read datasets of varying coverage and error profiles from an RSV reference genome. The datasets were spiked with nucleotide variants at predetermined positions and frequencies. Variants were called using FreeBayes, LoFreq, Vardict, and VarScan2. The variant callers' agreement in identifying known variants was quantified using two measures; concordance accuracy and the inter-caller concordance. Results: The variant callers reported differences in identifying minority variants from the datasets. Concordance accuracy and inter-caller concordance were positively correlated with sample coverage. FreeBayes identified the majority of variants although it was characterised by variable sensitivity and precision in addition to a high false positive rate relative to the other minority variant callers and which varied with sample coverage. LoFreq was the most conservative caller. Conclusions: We conducted a performance and concordance evaluation of four minority variant calling tools used to identify and quantify low frequency variants. Inconsistency in the quality of sequenced samples impacts on sensitivity and accuracy of minority variant callers. Our study suggests that combining at least three tools when identifying minority variants is useful in filtering errors when calling low frequency variants

Problematic use of the Internet is a unidimensional quasi-trait with impulsive and compulsive subtypes

Abstract: Background: Problematic use of the Internet has been highlighted as needing further study by international bodies, including the European Union and American Psychiatric Association. Knowledge regarding the optimal classification of problematic use of the Internet, subtypes, and associations with clinical disorders has been hindered by reliance on measurement instruments characterized by limited psychometric properties and external validation. Methods: Non-treatment seeking individuals were recruited from the community of Stellenbosch, South Africa (N = 1661), and Chicago, United States of America (N = 827). Participants completed an online version of the Internet Addiction Test, a widely used measure of problematic use of the Internet consisting of 20-items, measured on a 5-point Likert-scale. The online questions also included demographic measures, time spent engaging in different online activities, and clinical scales. The psychometric properties of the Internet Addiction Test, and potential problematic use of the Internet subtypes, were characterized using factor analysis and latent class analysis. Results: Internet Addiction Test data were optimally conceptualized as unidimensional. Latent class analysis identified two groups: those essentially free from Internet use problems, and those with problematic use of the Internet situated along a unidimensional spectrum. Internet Addiction Test scores clearly differentiated these groups, but with different optimal cut-offs at each site. In the larger Stellenbosch dataset, there was evidence for two subtypes of problematic use of the Internet that differed in severity: a lower severity “impulsive” subtype (linked with attention-deficit hyperactivity disorder), and a higher severity “compulsive” subtype (linked with obsessive-compulsive personality traits). Conclusions: Problematic use of the Internet as measured by the Internet Addiction Test reflects a quasi-trait - a unipolar dimension in which most variance is restricted to a subset of people with problems regulating Internet use. There was no evidence for subtypes based on the type of online activities engaged in, which increased similarly with overall severity of Internet use problems. Measures of comorbid psychiatric symptoms, along with impulsivity, and compulsivity, appear valuable for differentiating clinical subtypes and could be included in the development of new instruments for assessing the presence and severity of Internet use problems

Human rhinovirus spatial-temporal epidemiology in rural coastal Kenya, 2015-2016, observed through outpatient surveillance

Background Human rhinovirus (HRV) is the predominant cause of upper respiratory tract infections, resulting in a significant public health burden. The virus circulates as many different types (~160), each generating strong homologous, but weak heterotypic, immunity. The influence of these features on transmission patterns of HRV in the community is understudied. Methods Nasopharyngeal swabs were collected from patients with symptoms of acute respiratory infection (ARI) at nine out-patient facilities across a Health and Demographic Surveillance System between December 2015 and November 2016. HRV was diagnosed by real-time RT-PCR, and the VP4/VP2 genomic region of the positive samples sequenced. Phylogenetic analysis was used to determine the HRV types. Classification models and G-test statistic were used to investigate HRV type spatial distribution. Demographic characteristics and clinical features of ARI were also compared. Results Of 5,744 NPS samples collected, HRV was detected in 1057 (18.4%), of which 817 (77.3%) were successfully sequenced. HRV species A, B and C were identified in 360 (44.1%), 67 (8.2%) and 390 (47.7%) samples, respectively. In total, 87 types were determined: 39, 10 and 38 occurred within species A, B and C, respectively. HRV types presented heterogeneous temporal patterns of persistence. Spatially, identical types occurred over a wide distance at similar times, but there was statistically significant evidence for clustering of types between health facilities in close proximity or linked by major road networks. Conclusion This study records a high prevalence of HRV in out-patient presentations exhibiting high type diversity. Patterns of occurrence suggest frequent and independent community invasion of different types. Temporal differences of persistence between types may reflect variation in type-specific population immunity. Spatial patterns suggest either rapid spread or multiple invasions of the same type, but evidence of similar types amongst close health facilities, or along road systems, indicate type partitioning structured by local spread

Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation

Objective: Colorectal cancer (CRC) is a major contributor to cancer mortality and morbidity. LIM kinase 2 (LIMK2) promotes tumour cell invasion and metastasis. The objectives of this study were to determine how LIMK2 expression is associated with CRC progression and patient outcome, and to use genetically modified Drosophila and mice to determine how LIMK2 deletion affects gastrointestinal stem cell regulation and tumour development.<p></p> Design: LIMK2 expression and activity were measured by immunostaining tumours from CRC-prone mice, human CRC cell lines and 650 human tumours. LIMK knockdown in Drosophila or Limk2 deletion in mice allowed for assessment of their contributions to gastrointestinal stem cell homeostasis and tumour development.<p></p> Results: LIMK2 expression was reduced in intestinal tumours of cancer-prone mice, as well as in human CRC cell lines and tumours. Reduced LIMK2 expression and substrate phosphorylation were associated with shorter patient survival. Genetic analysis in Drosophila midgut and intestinal epithelial cells isolated from genetically modified mice revealed a conserved role for LIMK2 in constraining gastrointestinal stem cell proliferation. Limk2 deletion increased colon tumour size in a colitis-associated colorectal mouse cancer model.<p></p> Conclusions: This study revealed that LIMK2 expression and activity progressively decrease with advancing stage, and supports the hypothesis that there is selective pressure for reduced LIMK2 expression in CRC to relieve negative constraints imposed upon gastrointestinal stem cells.<p></p&gt