Citations

Building on diamond characteristics such as hardness, chemical inertness and low electron emission threshold voltage, the current microscopic, spectroscopic and voltammetric investigations are directed towards improving the properties of electrode coating materials for their future use in clinical studies of deep brain stimulation via fast-scan cyclic voltammetry (FSCV). In this study we combine the capabilities of confocal Raman mapping in providing detailed and accurate analysis of local distributions of material constituents in a series of boron-doped polycrystalline diamond films grown by chemical vapor deposition, with information from the more conventional techniques of scanning electron microscopy (SEM) and infrared absorption spectroscopy. Although SEM images show a uniform distribution of film crystallites, they have the limitation of being unable to differentiate the distribution of boron in the diamond. Values of 1018–1021 atoms/cm3 of boron content have been estimated from the absorption coefficient of the 1290 cm−1 infrared absorption band and from the 500 cm−1 Raman vibration. The observed accumulation of boron atoms and carbon sp2 impurities at the grain boundaries suggests that very high doping levels do not necessarily contribute to improvement of the material’s conductivity, corroborating with voltammetric data. FSCV results also indicate an enhanced stability of analyte detection.

Background Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P <0.0001), more likely to be white (92% versus 89%, P =0.005), more likely to have private insurance (33% versus 25%, P <0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P <0.0001). They had more new‐onset atrial fibrillation (8.8% versus 4.1%, P <0.0001), lower CHADS 2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P <0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P <0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P =0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P <0.0001). Conclusions Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL : Clinicaltrials.gov. Unique identifier: NCT 01165710.

Abstract A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76–0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75–0.95; P = 0.006). Considering a multiple-testing–corrected significance threshold of P &lt; 2.5 × 10−5, only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79–0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852–61. ©2013 AACR.

ABSTRACTGenes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene‐environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P‐values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.

Abstract Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P &lt; 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P &lt; 10−4) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P &lt; 10−8. Results from the second analytic approach were consistent with those from the first (P &gt; 10−10). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.

AbstractBackgroundWe examined the course of cutaneous T‐cell lymphoma (CTCL), which has been associated with chronic lymphocytic leukemia (CLL) in patients withCLL.Materials and methodsA search was conducted of the master diagnosis index at our institution to identify patients with bothCLLandCTCLfrom 1980 to 2010. A retrospective chart review was then conducted.ResultsOf the 14 patients withCTCLandCLL, eight had mycosis fungoides (MF; two with patch stage, two with plaque stage, two with tumor stage, and two with erythrodermic stage), four had Sézary syndrome, one had natural killer cell lymphoma involving the skin, and one had peripheral T‐cell lymphoma involving the skin. Eight had concurrent diagnoses, five received aCLLdiagnosis first, and one received aCTCLdiagnosis first. Ten patients were deceased at the time of data abstraction due to unknown causes (n = 4), lymphoma (n = 2), pneumonia (n = 2),MF(n = 1), or respiratory failure (n = 1). Of the nine patients with concurrent or priorCTCL, seven were deceased, with a median time to death of 10.2 months (range, 6–89 months). Of the five patients withCLLprior toCTCL, three were deceased at 18, 27, and 47 months, respectively, after theCTCLdiagnosis. The median survival for the two groups was 12 and 47 months, respectively.ConclusionsPatients withCTCLconcurrent with or prior toCLLhave a worse overall survival than patients withCLLin whomCTCLlater develops. Larger studies are needed.