High-resolution simulations of population-density change with an activity-based cellular automata land-use model

The MOLAND model is a cellular automata (CA) land-use change model that has often been applied to simulate urban growth. A more recent alternative model makes the simulations more multifunctional by also computing different activities (population and employment) for every cell. However, the equation to update population density in time in this activity-based CA model could not deal with high population growth rates in some existing urban centres. Therefore, we experimented with two alternative equations. A semi-automated calibration routine was used to compare errors of the different model versions at a continuous range of resolutions in two study areas: the Greater Dublin Region, Ireland, and Flanders and Brussels, Belgium. The two new population density equations turn out to solve the particular problem of fast changes in high-density neighbourhoods and generally improve regional errors in the Belgian application, but can unfortunately introduce larger errors in low-density areas or in the land-use simulations

A travel time-based variable grid approach for an activity-based cellular automata model

Urban growth and population growth are used in numerous models to determine their potential impacts on both the natural and the socio-economic systems. Cellular automata (CA) land-use models became popular for urban growth modelling since they predict spatial interactions between different land uses in an explicit and straightforward manner. A common deficiency of land-use models is that they only deal with abstract categories, while in reality, several activities are often hosted at one location (e.g. population, employment, agricultural yield, nature…). Recently, a multiple activity-based variable grid CA model was proposed to represent several urban activities (population and economic activities) within single model cells. The distance-decay influence rules of the model included both short- and long-distance interactions, but all distances between cells were simply Euclidean distances. The geometry of the real transportation system, as well as its interrelations with the evolving activities, were therefore not taken into account. To improve this particular model, we make the influence rules functions of time travelled on the transportation system. Specifically, the new algorithm computes and stores all travel times needed for the variable grid CA. This approach provides fast run times, and it has a higher resolution and more easily modified parameters than the alternative approach of coupling the activity-based CA model to an external transportation model. This paper presents results from one Euclidean scenario and four different transport network scenarios to show the effects on land-use and activity change in an application to Belgium. The approach can add value to urban scenario analysis and the development of transport- and activity-related spatial indicators, and constitutes a general improvement of the activity-based CA model

Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and FTD

OBJECTIVE: To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD). METHODS: Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing. RESULTS: We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype. CONCLUSIONS: A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early-onset dementia with prominent frontal lobe and motor symptoms

Grammar disruption in a patient with Neuro-Sweet syndrome

This paper for the first time reports detailed neurolinguistic findings in a patient with Neuro-Sweet syndrome. In this patient the presenting symptoms of central nervous system (CNS) involvement primarily consisted of a selective grammar deficit restricted to spontaneous speech. On MRI a left prefrontal ischemic stroke (superior part BA 6) and two small subcortical left parietal infarctions were found. Neurolinguistic analyses, however, did not reveal a profile consistent with any observations of agrammatism caused by structural damage to the language areas critically involved in grammatical processing. It is hypothesized that selectively distorted grammar might reflect disruption of the frontosubcortical network involved in language processing. Prefrontal neurobehavioral abnormalities associated with functional disruption of the inferior medial frontal regions as demonstrated by SPECT, additionally suggest that agrammatic symptoms may be linked to a higher-level cognitive disorder following encephalopathic CNS involvement

The ‘Exposed’ Population, Violent Crime in Public Space and the Night-time Economy in Manchester, United Kingdom

The daily rhythms of the city, the ebb and flow of people undertaking routines activities, inform the spatial and temporal patterning of crime. Being able to capture citizen mobility and delineate a crime-specific population denominator is a vital prerequisite of the endeavour to both explain and address crime. This paper introduces the concept of an exposed population-at-risk, defined as the mix of residents and non-residents who may play an active role as an offender, victim or guardian in a specific crime type, present in a spatial unit at a given time. This definition is deployed to determine the exposed population-at-risk for violent crime, associated with the night-time economy, in public spaces. Through integrating census data with mobile phone data and utilising fine-grained temporal and spatial violent crime data, the paper demonstrates the value of deploying an exposed (over an ambient) population-at-risk denominator to determine violent crime in public space hotspots on Saturday nights in Greater Manchester (UK). In doing so, the paper illuminates that as violent crime in public space rises, over the course of a Saturday evening, the exposed population-at-risk falls, implying a shifting propensity of the exposed population-at-risk to perform active roles as offenders, victims and/or guardians. The paper concludes with a discussion of the theoretical and policy relevance of these findings

Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability

Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal fring as culprits of neurodegeneration. In this study, we used paired-end short-read and direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family signifcantly linked to 7q36. We identifed and validated a chromosomal inversion of ca. 4 Mb, segregating on the disease haplotype and disrupting the coding sequence of dipeptidyl-peptidase 6 gene (DPP6). DPP6 resequencing identifed signifcantly more rare variants—nonsense, frameshift, and missense—in early-onset Alzheimer’s disease (EOAD, p value=0.03, OR=2.21 95% CI 1.05–4.82) and frontotemporal dementia (FTD, p=0.006, OR=2.59, 95% CI 1.28–5.49) patient cohorts. DPP6 is a type II transmembrane protein with a highly structured extracellular domain and is mainly expressed in brain, where it binds to the potassium channel Kv4.2 enhancing its expression, regulating its gating properties and controlling the dendritic excitability of hippocampal neurons. Using in vitro modeling, we showed that the missense variants found in patients destabilize DPP6 and reduce its membrane expression (p<0.001 and p<0.0001) leading to a loss of protein. Reduced DPP6 and/or Kv4.2 expression was also detected in brain tissue of missense variant carriers. Loss of DPP6 is known to caus