Spatial Economics: Density, Potential, and Flow

Location theory has traditionally considered space as a two-dimensional Euclidean continuum. It has resorted to geometric constructions and emphasized geometric and geographic intuition. More recently, the emergence of linear and mathematical programming methods in regional analysis has favored an abstract indexing of locations. The matrix of spatial relationships has become the matrix of point-pairs. But the intuitive notions of two-dimensional space have been lost in the process. The purpose of this book is to reintroduce the two-dimensional continuum as the natural spatial setting of economic activities and to exploit the idea for all its worth. Economic interaction between agents are viewed as flows, of commodities or persons. These flows are generated by production and consumption activities, which represent the sources and sinks of a flow field. The direction of flow is oriented by principles of cost minimization and/or of profit or utility maximization. In this way neoclassical economics is wedded to the hydrodynamics of flow fields

Effekten av olika koncentrationer av Rotstop R och Rotstop S och ofullständig täckning av Rotstop S på sporinfektioner av rotticka på granstubbar

The effectiveness of treatment with two Phlebiopsis gigantea based preparations (Rotstop® and RotstopS) in different concentrations against the root and butt rot causing fungus Heterobasidion annosum s.l. on Norway spruce (Picea abies) thinning stumps in southern Sweden was compared. The trees were cut on three sites during the summer 2004 and 285 stumps were treated manually with 100% cover with two different amounts of spores in solution corresponding to approximately 5×106 spores/l and 10×106 spores/l. 31 stumps received mechanical part cover with the highest spore concentrations of Phlebiopsis gigantea, i.e. approximately 20×106 spores/l. Mechanical treatment was assessed for satisfactory treatment effect. Three months later, samples were collected and analyzed. There was a significant reduction in frequency and relative areas of Heterobasidion spp. infections on stumps with manual application of control agents compared to untreated stumps. On average 10 to 23% of stumps subjected to manual treatments were infected compared to 52% for the untreated stumps. However, none of the concentration solutions of Rotstop® and RotstopS differed from the others in reduction of Heterobasidion spp. infections. Mechanical treatment failed to control the Heterobasidion spp. infections, but there was a tendency for the 85.1-95.0% cover class to provide better result than the others. Thus, despite of the incomplete control of the pathogen, stump treatment with different concentrations of Phlebiopsis gigantea oidia in suspensions provided equal effects at the present spore loads of Heterobasidion spp.Effektiviteten av behandling med två pergamentsvampsbaserade (Phlebiopsis gigantea) lösningar (Rotstop® och RotstopS) i olika koncentrationer mot sporinfektioner av rotticka (Heterobasidion spp.) på gallringsstubbar av gran (Picea abies) i södra Sverige jämfördes. Träd avverkades på tre olika lokaler under sommaren 2004 och sammanlagt 285 stubbar behandlades manuellt med en hundraprocentig täckning i två olika koncentrationer motsvarande ungefär 5×106 sporer/l respektive 10×106 sporer/l lösning. 31 stubbar på en av lokalerna behandlades maskinellt med en ofullständig täckning men med den högsta koncentrationen av pergamentsvamp (RotstopS), ca 20×106 sporer/l lösning. Effekten av den mekaniska behandlingens partiella täckning jämfördes med den manuella fullständiga. Tre månader efter behandlingen samlades prover in för analys med avseende på förekomsten av rotticka. Alla manuella behandlingar gav en signifikant reducering av frekvensen av och relativa arean av rottickeinfektioner jämfört med obehandlade stubbar. I genomsnitt var 10 till 23 % av de manuellt behandlade stubbarna infekterade jämfört med 52 % av de obehandlade. Ingen av de manuella applikationerna skiljde sig dock från varandra. Den mekaniska behandlingen gav inte ett tillfredsställande resultat men det fanns en tendens till att täckningsgradsklass 85,1- 95,0 % fungerade bättre än de andra. Således, trots att ingen behandling gav en 100 % -ig minskning av antalet rottickeinfektioner, verkar olika koncentrationer av Rotstop® och RotstopS ge ett likvärdigt resultat under de förhållanden i sportryck som rådde vid behandlingen

Nash Equilibria in Discrete Routing Games with Convex Latency Functions

In a discrete routing game, each of n selfish users employs a mixed strategy to ship her (unsplittable) traffic over m parallel links. The (expected) latency on a link is determined by an arbitrary non-decreasing, non-constant and convex latency function φ. In a Nash equilibrium, each user alone is minimizing her (Expected) Individual Cost, which is the (expected) latency on the link she chooses. To evaluate Nash equilibria, we formulate Social Cost as the sum of the users ’ (Expected) Individual Costs. The Price of Anarchy is the worst-case ratio of Social Cost for a Nash equilibrium over the least possible Social Cost. A Nash equilibrium is pure if each user deterministically chooses a single link; a Nash equilibrium is fully mixed if each user chooses each link with non-zero probability. We obtain: For the case of identical users, the Social Cost of any Nash equilibrium is no more than the Social Cost of the fully mixed Nash equilibrium, which may exist only uniquely. Moreover, instances admitting a fully mixed Nash equilibrium enjoy an efficient characterization. For the case of identical users, we derive two upper bounds on the Price of Anarchy: For the case of identical links with a monomial latency function φ(x) = x d, the Price of Anarchy is the Bell number of order d + 1. For pure Nash equilibria, a generic upper bound from the Wardrop model can be transfered to discrete routing games. For polynomial latency functions with non-negative coefficients and degree d, this yields an upper bound of d + 1. For th

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results:Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95 confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion:Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. © 2014 Cancer Research UK

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.

IMPORTANCE: The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits

PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1

Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.Peer reviewe

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

Fine-Scale Mapping of the 5q11.2 Breast Cancer Locus Reveals at Least Three Independent Risk Variants Regulating MAP3K1

Peer reviewe