Guidelines for assessing pedestrian evacuation software applications

This paper serves to clearly identify and explain criteria to consider when evaluating the suitability of a pedestrian evacuation software application to assess the evacuation process of a building. Guidelines in the form of nine topic areas identify different modelling approaches adopted, as well as features / functionality provided by applications designed specifically for simulating the egress of pedestrians from inside a building. The paper concludes with a synopsis of these guidelines, identifying key questions (by topic area) to found an evaluation

A worldwide correlation of lactase persistence phenotype and genotypes

Background: The ability of adult humans to digest the milk sugar lactose - lactase persistence - is a dominant Mendelian trait that has been a subject of extensive genetic, medical and evolutionary research. Lactase persistence is common in people of European ancestry as well as some African, Middle Eastern and Southern Asian groups, but is rare or absent elsewhere in the world. The recent identification of independent nucleotide changes that are strongly associated with lactase persistence in different populations worldwide has led to the possibility of genetic tests for the trait. However, it is highly unlikely that all lactase persistence-associated variants are known. Using an extensive database of lactase persistence phenotype frequencies, together with information on how those data were collected and data on the frequencies of lactase persistence variants, we present a global summary of the extent to which current genetic knowledge can explain lactase persistence phenotype frequency. Results: We used surface interpolation of Old World lactase persistence genotype and phenotype frequency estimates obtained from all available literature and perform a comparison between predicted and observed trait frequencies in continuous space. By accommodating additional data on sample numbers and known false negative and false positive rates for the various lactase persistence phenotype tests (blood glucose and breath hydrogen), we also apply a Monte Carlo method to estimate the probability that known lactase persistence-associated allele frequencies can explain observed trait frequencies in different regions. Conclusion: Lactase persistence genotype data is currently insufficient to explain lactase persistence phenotype frequency in much of western and southern Africa, southeastern Europe, the Middle East and parts of central and southern Asia. We suggest that further studies of genetic variation in these regions should reveal additional nucleotide variants that are associated with lactase persistence

Consequences of Uncertainty in Global-Scale Land Cover Maps for Mapping Ecosystem Functions: An Analysis of Pollination Efficiency

Mapping ecosystem services (ESs) is an important tool for providing the quantitative information necessary for the optimal use and protection of ecosystems and biodiversity. A common mapping approach is to apply established empirical relationships to ecosystem property maps. Often, ecosystem properties that provide services to humanity are strongly related to the land use and land cover, where the spatial allocation of the land cover in the landscape is especially important. Land use and land cover maps are, therefore, essential for ES mapping. However, insight into the uncertainties in land cover maps and how these propagate into ES maps is lacking. To analyze the effects of these uncertainties, we mapped pollination efficiency as an example of an ecosystem function, using two continental-scale land cover maps and two global-scale land cover maps. We compared the outputs with maps based on a detailed national-scale map. The ecosystem properties and functions could be mapped using the GLOBCOVER map with a reasonable to good accuracy. In homogeneous landscapes, an even coarser resolution map would suffice. For mapping ESs that depend on the spatial allocation of land cover in the landscape, a classification of satellite images using fractional land cover or mosaic classes is an asset

Estimates of distance by claudicants and vascular surgeons are inherently unreliable

Claudication distance and maximum walking distance are both measures of disability. Estimates of the distances which a patient with intermittent claudication can walk are commonly used by vascular surgeons as surrogate measures of handicap. We studied how accurately distance was estimated by 70 patients with intermittent claudication, and by 100 British vascular surgeons.Patients and vascular surgeons estimated actual distances of 30 m and 34 m, respectively. Estimates were 46 m median (range 2.7–402 m) for claudicants, and 46 m median (range 15.2–186 m) for vascular surgeons, median over estimates of 52% and 34% respectively. Claudicants' errors can easily be eliminated by accurate and appropriate measurement of claudication and maximum walking distances but interpretation of the data by surgeons is dependent on their own ability to estimate distance. Flawed perceptions by patients and their surgeons of the disability of reduced walking distance illustrates the need for reliable measures of handicap on which to base therapeutic decisions in patients with intermittent claudication

Biosynthetic studies on tropic acid and piliformic acid

This thesis is divided into two parts and covers biosynthetic studies on two secondary metabolites, tropic acid in Part I and piliformic acid, in Part II.(S)-Tropic acid is the acid moiety of the alkaloids hyoscyamine and scopolamine, which are produced by a number of plants of the Solanacae family. An intriguing rearrangement of the L-phenylalanine side chain gives rise to the isopropanoid (S)-tropic acid skeleton. The detailed nature of the rearrangement has however remained elusive despite continued interest over the years. In chapter two the identification of intermediates between L-phenylalanine and (S)-tropic acid is discussed, which has placed (R)-D-phenyllactic acid as an immediate precursor. The stereochemical features of the rearrangement are described in chapter 3 and finally in chapter 4 a mechanism for the rearrangement is proposed. This is based on information obtained from the incorporation of various isotopically labelled precursors to tropic acid into two of the minor alkaloids, 3a-2'-hydroxyacetoxytropane and 3a- phenylacetoxytropane. This work was carried out in collaboration with Dr Richard Robins at the AFRC Institute of Food Research in Norwich. Piliformic acid is elaborated by the slow growing fungus Poronia piliformis. The incorporation of a number of isotopically labelled substrates into piliformic acid has revealed a mixed biosynthetic origin, comprising C(_8) and C(_3) fragments. These have been shown to be of acetogenic and citric acid cycle origins respectively. The C(_8) fragment has been further demonstrated to be a degradation product of a longer chain fatty acid. The mode of coupling of the two fragments has been investigated and suggests the intermediacy of a novel a-carboxyoctanoate. A pathway for the assembly of piliformic acid, involving a 1,3-hydrogen shift, is proposed, consistent with the above findings. These results are the subject of chapter 6

The evolutionary genetics of lactase persistence in Africa and the Middle East.

Lactase, the enzyme responsible for milk digestion, is expressed in the small intestine of nearly all neonate mammals, and normally down-regulates following weaning. This is the ancestral state and in humans is described as lactase non-persistent. However, some people continue to have high expression of the enzyme for life due to a genetically inherited variation known as lactase persistence. A single nucleotide polymorphism, -13910*T was identified as the causal variation in Europeans due to a very tight association with phenotype and evidence of a functional effect in vitro. Subsequently, an apparent disparity was observed between -13910*T frequency and reported lactase persistence frequency in some African populations, raising doubts about the causal nature of the allele. Two possible explanations were proposed either -13910*T is not causal, but in Europeans is tightly linked to the true cause of lactase persistence, or, -13910*T is causal in Europeans, but the trait has evolved independently elsewhere. The primary aim of this thesis was to investigate the causes of lactase persistence in sub-Saharan Africa. The occurrence of only one -13910*T carrier out of 45 lactase persistent people from a cohort of phenotyped Sudanese individuals provided confirmation that the allele is not causal worldwide. Haplotype analysis of a 70kb region spanning the lactase gene in the phenotyped cohort and in non-European pastoralist groups provided no evidence for a shared origin with the European mutation. Resequencing of the -13910 locus led to the identification of a number of candidate SNPs -13915T>G, -13913T>C and -13907C>G, all located within 5bp of the original variant. Despite being clustered within the same OCT1 protein binding site as -13910*T, gel shift experiments revealed that the new alleles did not have a common effect on protein binding. However, -13915*G showed a significant association with lactase persistence. Resequencing of a second phenotyped cohort revealed the presence of many variant alleles at the locus, the occurrence of which is significantly higher in persistent individuals. Nearly every allele associates with an independent haplotype, providing strong evidence that multiple unrelated evolutionary events gave rise to lactase persistence. The frequency and distribution of all newly identified alleles was surveyed in more than 700 individuals from a total of 18 African and Middle Eastern populations, and gives a preliminary indication of the geographic origin of some alleles. The clustering of lactase persistence associated alleles within a single regulatory element implies that they are causal, and possible mechanisms and future approaches are discussed

Mapping ecosystem functions and services in Eastern Europe using global-scale data sets

To assess future interactions between the environment and human well-being, spatially explicit ecosystem service models are needed. Currently available models mainly focus on provisioning services and do not distinguish changes in the functioning of the ecosystem (Ecosystem Functions – ESFs) and human use of such functions (Ecosystem Services – ESSs). This limits the insight on the impact of global change on human well-being. We present a set of models for assessing ESFs and ESSs. We mapped a diverse set of provisioning, regulating and cultural services, focusing on services that depend on the landscape structure. Services were mapped using global-scale data sets. We evaluated the models for a sample area comprising Eastern Europe. ESFs are mainly available in natural areas, while hotspots of ESS supply are found in areas with heterogeneous land cover. Here, natural land cover where ESFs are available is mixed with areas where the ESSs are utilized. We conclude that spatial patterns of several ESFs and ESSs can be mapped at global scale using existing global-scale data sets. As land-cover change has different impacts on different aspects of the interaction between humans and the environment, it is essential to clearly distinguish between ESFs and ESSs in integrated assessment studies