Tensor Products, Positive Linear Operators, and Delay-Differential Equations

We develop the theory of compound functional differential equations, which are tensor and exterior products of linear functional differential equations. Of particular interest is the equation $\dot x(t)=-\alpha(t)x(t)-\beta(t)x(t-1)$ with a single delay, where the delay coefficient is of one sign, say $\delta\beta(t)\ge 0$ with $\delta\in{-1,1}$. Positivity properties are studied, with the result that if $(-1)^k=\delta$ then the $k$-fold exterior product of the above system generates a linear process which is positive with respect to a certain cone in the phase space. Additionally, if the coefficients $\alpha(t)$ and $\beta(t)$ are periodic of the same period, and $\beta(t)$ satisfies a uniform sign condition, then there is an infinite set of Floquet multipliers which are complete with respect to an associated lap number. Finally, the concept of $u_0$-positivity of the exterior product is investigated when $\beta(t)$ satisfies a uniform sign condition.Comment: 84 page

A Metric Inequality for the Thompson and Hilbert Geometries

There are two natural metrics defined on an arbitrary convex cone: Thompson's part metric and Hilbert's projective metric. For both, we establish an inequality giving information about how far the metric is from being non-positively curved.Comment: 15 pages, 0 figures. To appear in J. Inequalities Pure Appl. Mat

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Globalization, educational targeting and stable inequalities : a comparative analysis of Argentina, Brazil and Chile

This article analyzes educational targeting in Argentina, Brazil and Chile from a sociological point of view. In essence, it presents the 'logic of induction' as an ideal type. This pedagogic discourse is the vehicle of an educational anti-poverty strategy that expects to induce clearly targeted groups to improve on their own. The analysis explores the influence of the global educational agenda, the empirical connection between this discourse and the mechanism of emulation as well as the territorialization of educational inequality. Emulation plays the main role inasmuch as the logic of induction eventually leads the target groups to compare their adverse situation with more privileged groups, what legitimizes the current structures of categorical inequality (Tilly 1998). Finally, a brief statistical summary reports that the trends of educational inequality have remained stable as far as urban- rural ratios (in Brazil and Chile) and regional disparities (in the three countries) are concerned

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352