ABSTRACT
Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004Subject(s)
Chorioretinitis/genetics
, Genetic Predisposition to Disease/genetics
, Receptors, Purinergic P2/genetics
, Toxoplasmosis, Congenital/genetics
, Adult
, Brazil
, Child, Preschool
, Chorioretinitis/etiology
, Female
, Genome-Wide Association Study
, Haplotypes/genetics
, Humans
, Inheritance Patterns/genetics
, Linkage Disequilibrium
, Logistic Models
, Male
, North America
, Polymorphism, Single Nucleotide/genetics
, Receptors, Purinergic P2X7
, Toxoplasmosis, Congenital/complications
ABSTRACT
Displacement corrections for in-phantom measurements with ionisation chambers for the purpose of mammography are large and represent a major correction to consider for dose determinations. Experimental data on displacement corrections depend to a large degree on the model used to extrapolate to zero cavity radius. Calculations of displacement correction factors using a Monte Carlo code are presented for different cavity shapes, i.e. spherical, cylindrical and disc-like, in various phantom materials simulating the average breast and breast composing tissues. In addition, the influence of wall material and depth in-phantom are studied. Exponential extrapolation to zero cavity radius should be performed to obtain the dose in homogeneous phantoms. Displacement corrections for photons as used in mammography seem compatible with geometrical considerations made previously. A discrepancy is found between depth-dose data derived from calculations and those found in experiments.
