Optimal experimental design for joint reflection-transmission ultrasound breast imaging: From ray- to wave-based methods.

Ultrasound computed tomography (USCT) is an emerging modality to image the acoustic properties of the breast tissue for cancer diagnosis. With the need of improving the diagnostic accuracy of USCT, while maintaining the cost low, recent research is mainly focused on improving (1) the reconstruction methods and (2) the acquisition systems. D-optimal sequential experimental design (D-SOED) offers a method to integrate these aspects into a common systematic framework. The transducer configuration is optimized to minimize the uncertainties in the estimated model parameters, and to reduce the time to solution by identifying redundancies in the data. This work presents a formulation to jointly optimize the experiment for transmission and reflection data and, in particular, to estimate the speed of sound and reflectivity of the tissue using either ray-based or wave-based imaging methods. Uncertainties in the parameters can be quantified by extracting properties of the posterior covariance operator, which is analytically computed by linearizing the forward problem with respect to the prior knowledge about parameters. D-SOED is first introduced by an illustrative toy example, and then applied to real data. This shows that the time to solution can be substantially reduced, without altering the final image, by selecting the most informative measurements.

Triclinic polymorph of 4-[4-(4-formyl-phen-oxy)but-oxy]benzaldehyde.

The title compound, C18H18O4, is a triclinic polymorph of the previously reported monoclinic polymorph [Han & Zhen (2005 ▶). Acta Cryst. E61, o4358-o4359]. In the crystal of the triclinic polymorph, molecules are linked by two pairs of C-H⋯O hydrogen bonds, forming a two-dimensional network parallel to (102), and enclosing loops with graph set motifs of R2(2)(8) and R2(2)(6).

4-[5-(4-Formyl-phen-oxy)pent-oxy]benzaldehyde.

In the title compound, C(20)H(19)O(4), the benzene rings, linked via five methyl-ene C atoms, form a dihedral angle of 77.28 (6)°. In the crystal, mol-ecules are linked via pairs of weak C-H⋯O inter-actions [graph set R(2) (2)(6)] into dimers that are further connected by additional weak C-H⋯O interactions [graph sets R(2) (2)(14), R(2) (2)(26) and R(2) (2)(6)].

Semaphorin 3B and 3F single nucleotide polymorphisms are associated with prostate cancer risk and poor prognosis.

PURPOSE: SEMA3B and SEMA3F are 2 closely related genes lying 80 kb apart on chromosome 3 that have been shown to suppress tumor formation in vivo and in vitro. Each gene has a single nucleotide polymorphism that results in a nonsynonymous coding change, rs2071203 (SEMA3B) and rs1046956 (SEMA3F), as well as noncoding single nucleotide polymorphisms. MATERIALS AND METHODS: We performed a case-control study of 789 prostate cancer cases and 907 controls from 3 races/ethnicities to determine possible associations of 10 variants with prostate cancer risk or prognosis. RESULTS: The risk of prostate cancer increased more than 2-fold in Hispanic men with TT alleles at rs2071203 in SEMA3B and with CC alleles for rs2072054 at the 5' end of SEMA3F (OR 2.13, 95% CI 1.12-4.04, p = 0.02 and OR 2.55, 95% CI 1.34-4.84, p = 0.0045, respectively). These 2 single nucleotide polymorphisms were also associated with a poor prognosis in Hispanic men (2.71 and 3.48-fold increased risk). A frequent G-C-G-G-A-T-C-C-T-G haplotype encompassing 10 SNPs was associated with an increased risk of prostate cancer and poor prognosis in Hispanic samples (OR 2.72, 95% CI 1.20-6.12, p = 0.016 and OR 3.32, 95% CI 1.21-9.10, p = 0.02). In nonHispanic white men the T-C-G-A-A-T-C-C haplotype was associated with a high Gleason score (OR 1.44, 95% CI 1.06-1.96, p = 0.021). CONCLUSIONS: These data indicate that polymorphisms in SEMA3B and SEMA3F are associated with prostate cancer risk and poor prognosis in Hispanic and nonHispanic white men.

VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-Hispanic White and Hispanic White men.

PURPOSE: Vitamin D and dihydrotestosterone pathways interact to promote the growth of prostatic tissue. The nuclear vitamin D receptor (VDR) moderates the actions of vitamin D. 5alpha-Reductase type II (SRD5A2) codes for the enzyme that converts testosterone to dihydrotestosterone in the prostate. This study tested the interactions of VDR (CDX2, FokI) and SRD5A2 (V89L, A49T) polymorphisms, and their associations with prostate cancer. EXPERIMENTAL DESIGN: This genetic association study included 932 non-Hispanic White (NHW) men and 414 Hispanic White (HW) men from South Texas. Cases had biopsy-confirmed cancer; controls had normal digital rectal exams and serum prostate-specific antigen levels of <2.5 ng/mL. RESULTS: Using logistic regression analyses to test associations with prostate cancer, only the V89L polymorphism (VV genotype compared with LL/LV) in HW men was statistically significant [odds ratios (OR), 0.64; 95% confidence intervals (95% CI), 0.41-0.99]. The interaction terms for FokI and V89L in NHW men and CDX2 and V89L in HW men in the logistic model were significant (P = 0.02 and 0.03, respectively). When stratified by V89L genotype, the FokI polymorphism (TT/TC versus CC) was significantly associated with prostate cancer in NHW men with the V89L VV genotype (FokI OR, 1.53; 95% CI, 1.06-2.23). The CDX2 polymorphism (GG versus AG/AA) was significantly associated with prostate cancer only in HW men with the V89L VV genotype (CDX2 OR, 3.16; 95% CI, 1.39-7.19; interaction term P = 0.02). CONCLUSION: Our results indicate that the SRD5A2 V89L VV genotype interacts with VDR FokI TT/CT genotypes in NHW men and VDR CDX2 GG genotypes in HW men to increase the risk for prostate cancer.

CYP1B1 variants are associated with prostate cancer in non-Hispanic and Hispanic Caucasians.

Cytochrome P450 1B1 (CYP1B1) is involved in the activation of many carcinogens and in the metabolism of steroid hormones. We compared allele, genotype and haplotype frequencies of six single-nucleotide polymorphisms (SNPs) within CYP1B1 among non-Hispanic Caucasians (496 cases and 498 controls) and Hispanic Caucasians (153 cases and 240 controls). In the Hispanic Caucasians, the GG genotype for rs1056836 decreased the risk for prostate cancer (PCa) when compared with the CC genotype [odds ratio (OR) = 0.31, P = 0.04, 95% confidence interval (CI) = 0.10-0.96]. Among non-Hispanic Caucasian men with more aggressive PCa, the prevalence of several SNPs (rs2567206, rs2551188, rs2617266, rs10012 and rs1056836) was significantly associated with the disease status. A common C-G-C-C-G-A haplotype for rs2567206-rs2551188-rs2617266-rs10012-rs1056836-rs1800440 showed an inverse association with PCa risk in Hispanic Caucasians (OR = 0.19, P = 0.04, 95% CI = 0.04-0.95) and with aggressive disease status (i.e. Gleason score >or=7) in non-Hispanic Caucasian cases (OR = 0.64, P = 0.008, 95% CI = 0.47-0.89). In the non-Hispanic Caucasian cases, a second major haplotype T-A-T-G-C-A was positively associated with the high-grade disease status (OR = 1.77, P = 0.002, 95% CI = 1.24-2.53). Our findings suggest that genetic polymorphisms in CYP1B1 may modify the risk for PCa and support the role of CYP1B1 as a candidate gene for PCa.

Association between an estrogen receptor alpha gene polymorphism and the risk of prostate cancer in black men.

PURPOSE: Studies suggest that SNPs within ESR1 may be associated with an increased risk of prostate cancer. We evaluated the association of the XbaI and PvuII ESR1 SNPs and prostate cancer risk in 3 different racial/ethnic populations. MATERIALS AND METHODS: A total of 1,603 volunteers from the SABOR study (285 black, 876 white and 442 Hispanic men) were genotyped to assess allelic frequencies of the ESR1 SNPs. Case-control analysis was performed on 598 prostate cancer cases and 1,098 controls (260 black men, 1,013 non-Hispanic white men and 423 Hispanic white men) to assess the association between these polymorphisms and prostate cancer risk. RESULTS: Allelic frequency was significantly different across ethnic/racial groups for both SNPs. Logistic regression analysis adjusted for age and stratified by race and ethnicity demonstrated an association between the AG genotype or presence of the G allele (GG or AG genotype) in the XbaI SNP and prostate cancer risk within black men (OR 2.25, 95% CI 1.07-4.70, p = 0.031; OR 2.14, 95% CI 1.05-4.35, p = 0.035, respectively). No association was observed among Hispanic and non-Hispanic white men for this SNP. Furthermore, there was no association between the PvuII SNP and prostate cancer risk across all groups. CONCLUSIONS: Our study demonstrates an association between the AG genotype, as well as presence of the G allele within the XbaI ESR1 SNP and prostate cancer risk among black men.

Androgen receptor length polymorphism associated with prostate cancer risk in Hispanic men.

PURPOSE: The transcriptional activation domain of the androgen receptor gene includes a CAG repeat length polymorphism. A smaller number of repeats is reported to increase the risk of prostate cancer. We investigated the association of CAG repeat length and the risk of prostate cancer in a case-control study of Hispanic men. MATERIALS AND METHODS: To estimate the magnitude of the association of repeat length with prostate cancer risk, samples from 82 white patients of Hispanic origin (Hispanic) with prostate cancer and 145 Hispanic controls were genotyped. To determine the allelic distribution of repeats by race/ethnicity we genotyped 132 black men, 163 white men of nonHispanic origin (white) and 175 Hispanic men with no family history of prostate cancer, and performed pairwise comparison. RESULTS: In the case-control study of Hispanic men with a repeat length of 18 or less versus greater than 18 we found an approximately 3-fold increased risk of prostate cancer (OR 2.7, 95% CI 1.21 to 6.01, t test p = 0.013, age adjusted OR 3.03, 95% CI 1.27 to 7.26). The distribution of alleles differed significantly by race/ethnicity. The mean prevalence of short CAG repeat alleles plus or minus SD was higher in black than in white men (19.8 +/- 3.2 versus 21.8 +/- 2.7, t test p <0.0001) and lower in Hispanic men than in other white men (22.7 +/- 3.3, t test p = 0.014). CONCLUSIONS: To our knowledge, our study represents the first case-control study of the androgen receptor gene in a Hispanic population and provides evidence of the increased prostate cancer risk associated with short CAG repeats. Our results suggest that short CAG repeats are associated with an increased prostate cancer risk in Hispanic men.