Pedestrian demand modelling of large cities: an applied example from London

This paper introduces a methodology for the development of city wide pedestrian demand models and shows its application to London. The approach used for modelling is Multiple Regression Analysis of independent variables against the dependent variable of observed pedestrian flows. The test samples were from manual observation studies of average total pedestrian flow per hour on 237 sample sites. The model will provide predicted flow values for all 7,526 street segments in the 25 square kilometres of Central London. It has been independently validated by Transport for London and is being tested against further observation data. The longer term aim is to extend the model to the entire greater London area and to incorporate additional policy levers for use as a transport planning and evaluation tool

New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review.

The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments 'on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice

Mapping and Characterizing Subtidal Oyster Reefs Using Acoustic Techniques, Underwater Videography and Quadrat Counts

Populations of the eastern oyster Crassostrea virginica have been in long-term decline in most areas. A major hindrance to effective oyster management has been lack of a methodology for accurately and economically obtaining data on their distribution and abundance patterns. Here, we describe early results from studies aimed at development of a mapping and monitoring protocol involving acoustic techniques, underwater videography, and destructive sampling (excavated quadrats). Two subtidal reefs in Great Bay, New Hampshire, were mapped with side-scan sonar and with videography by systematically imaging multiple sampling cells in a grid covering the same areas. A single deployment was made in each cell, and a 5-10-s recording was made of a 0.25-m2 area; the location of each image was determined using a differential global position system. A still image was produced for each of the cells and all (n = 40 or 44) were combined into a single photomontage overlaid onto a geo-referenced base map for each reef using Arc View geographic information system. Quadrat (0.25 m2 ) samples were excavated from 9 or 10 of the imaged areas on each reef, and all live oysters were counted and measured. Intercomparisons of the acoustic, video, and quadrat data suggest: (1) acoustic techniques and systematic videography can readily delimit the boundaries of oyster reefs; (2) systematic videography can yield quantitative data on shell densities and information on reef structure; and (3) some combination of acoustics, systematic videography, and destructive sampling can provide spatially detailed information on oyster reef characteristics

Mathematical modelling of ethanol metabolism in normal subjects and chronic alcohol misusers

The time course of ethanol disappearance from the blood has been examined in normal males and females and in alcohol misusers. Blood alcohol estimations were made over a period of 3 hr, following an oral dose of ethanol (0.8 g/kg body weight) administered in the form of whisky. Attempts were made to fit the data to zero order, first order and mixed zero + first order kinetics. In the majority (75%) of normal females the blood ethanol concentration was still increasing at 30 min. This was only seen in 50% of normal males and in 50% of non-dependent alcohol misusers, but not in dependent alcohol misusers. In all of the normal females the disappearance of ethanol could be adequately described by zero order kinetics. However, in the normal male group only 20% could be described by zero order kinetics, 10% fitted first order kinetics and the remainder required a mixed model of zero + first order. The rate constant for the zero order component of the control male group was identical to zero order rate constant obtained for the female control group. In the female alcohol misuser group, 40% of the curves could not be described by zero order kinetics and fitted best to a mixed model. The zero order component of the entire group was significantly increased (by 35%) compared to that obtained for the female control group. In the male dependent and non-dependent alcohol misuser groups, all blood alcohol concentration curves fitted best to mixed zero and first order kinetics. However, no significant differences were noted in the values of the kinetic parameters when compared with the male control group. It is suggested that the zero order component of the blood alcohol concentration curves is due to the action of liver alcohol dehydrogenase and the first order component represents redistribution to the tissues. The presence or absence of a first order component is attributed to differences in absorption rates from the gut

A mathematical modelling study of an athlete's sprint time when towing a weighted sled

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s12283-013-0114-2.This study used a mathematical model to examine the effects of the sled, the running surface, and the athlete on sprint time when towing a weighted sled. Simulations showed that ratio scaling is an appropriate method of normalising the weight of the sled for athletes of different body size. The relationship between sprint time and the weight of the sled was almost linear, as long as the sled was not excessively heavy. The athlete’s sprint time and rate of increase in sprint time were greater on running surfaces with a greater coefficient of friction, and on any given running surface an athlete with a greater power-to-weight ratio had a lower rate of increase in sprint time. The angle of the tow cord did not have a substantial effect on an athlete’s sprint time. This greater understanding should help coaches set the training intensity experienced by an athlete when performing a sled-towing exercise

Estimation of linkage disequilibrium in a sample of the United Kingdom dairy cattle population using unphased genotypes

The association between genetic marker alleles was estimated for two regions of the bovine genome from a random sample of 50 young dairy bulls born in the United Kingdom between 1988 and 1995. Microsatellite marker genotypes were obtained for six markers on chromosome 2 and seven markers on chromosome 6, spanning 38 and 20 cM, respectively. Two different methods, which do not require family information, were used to estimate population haplotype frequencies. Haplotype frequencies were estimated for pairs of loci using the expectation-maximization algorithm and for all linked loci using a Bayesian approach via a Markov chain-Monte Carlo algorithm. Significant (P = 0.0007) linkage disequilibrium was detected between pairs of loci in syntenic groups (that is, loci in the same linkage group), extending to about 10 cM. No significant linkage disequilibrium was detected between markers in nonsyntenic regions. Given the observed level of linkage disequilibrium, mapping methods based on population-wide association might provide a better resolution than traditional quantitative trait loci mapping methods in the U.K. dairy cattle population and may reduce the required sample sizes of the experiments

Dental treatment and risk of variant CJD - a case control study

Abstract Objective: Knowledge of risk factors for variant CJD (vCJD) remains limited, but transmission of prion proteins via re-useable medical devices, including dental instruments, or enhanced susceptibility following trauma to the oral cavity is a concern. This study aimed to identify whether previous dental treatment is a risk factor for development of vCJD. Design: Case control study Methods: Risk factor questionnaires completed by interview with relatives of 130 vCJD patients and with relatives of 66 community and 53 hospital controls were examined by a dental surgeon. Responses regarding dental treatments were analysed. Results: We did not find a statistically significant excess of risk of vCJD associated with dental treatments with the exception of extractions in an unmatched analysis of vCJD cases with community controls (p=0.02). However, this result may be explained by multiple testing. Conclusions: This is the first published study to date to examine potential links between vCJD and dental treatment. There was no convincing evidence found of an increased risk of variant CJD associated with reported dental treatment. However, the power of the study is restricted by the number of vCJD cases to date and does not preclude the possibility that some cases have resulted from secondary transmission via dental procedures. Due to the limitations of the data available, more detailed analyses of dental records are required to fully exclude the possibility of transmission via dental treatment

Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

Background: There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon. Methods: Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth. Results: Neither genetic measure was associated with season or month of birth within the UKBB sample. Conclusions: As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure

IDO1 is an Integral Mediator of Inflammatory Neovascularization.

The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6). In this study, we investigated how genetic loss of IDO1 affects neovascularization in mouse models of oxygen-induced retinopathy and lung metastasis. Neovascularization in both models was significantly reduced in mice lacking IDO1, was similarly reduced with loss of IL6, and was restored in both cases by concomitant loss of IFNγ. Likewise, the lack of IDO1 or IL6 resulted in reduced metastatic tumor burden and increased survival, which the concomitant loss of IFNγ abrogated. This insight into IDO1\u27s involvement in pro-tumorigenic inflammatory neovascularization may have important ramifications for IDO1 inhibitor development, not only in cancer where clinical trials are currently ongoing, but in other disease indications associated with neovascularization as well

Limaria hians (Mollusca : Limacea): a neglected reef-forming keystone species

1. A key component of physical habitat along braided river systems is the exposed riverine sediment within the active zone. The relatively unmanaged, gravel-bed Fiume Tagliamento, Italy, provides the focus for exploring two ecologically important properties of exposed riverine sediments: their within-patch and between-patch variability in calibre. 2. To characterize between-patch variation in exposed riverine sediments, replicate (within-patch) samples were obtained from three geomorphologically distinct locations along 130 km of the river: bar heads along the margin of the low-flow channel, the heads of major bars across the exposed surface of the active zone, and floodplain surfaces. A photographic technique enabled rapid and consistent field sampling of the coarse sediments at bar heads along the low-flow channel margin and on major bars across the dry bed. 3. A downstream decrease in particle size and an increase in within-patch heterogeneity in sediment size were observed within bar head sediments along the margin of the low-flow channel. Comparisons between major bar and low-flow channel samples revealed greatest within-patch variability in individual sediment size indices (D50, A- and B-axes of the larger particles) at headwater sites, greatest between-patch variability in the three measured indices in the central reaches, and lowest between-patch variability at downstream sites. However, there was a distinct increase in the overall heterogeneity in particle size, which was sustained across all patches, in a downstream direction. 4. There was a clear downstream decrease in the size of floodplain sediments in the headwaters, but thereafter there was no distinct downstream trend in any of the calculated particle size indices. 5. The geomorphological controls on the observed patterns and the potential ecological significance of the patterns, particularly for plant establishment, are discussed in relation to the relative relief of the active zone, and the highly variable hydrological and climatic regime along the river