Sex-Related Differences in Violence Exposure, Neural Reactivity to Threat, and Mental Health

The prefrontal cortex (PFC), hippocampus, and amygdala play an important role in emotional health. However, adverse life events (e.g., violence exposure) affect the function of these brain regions, which may lead to disorders such as depression and anxiety. Depression and anxiety disproportionately affect women compared to men, and this disparity may reflect sex differences in the neural processes that underlie emotion expression and regulation. The present study investigated sex differences in the relationship between violence exposure and the neural processes that underlie emotion regulation. In the present study, 200 participants completed a Pavlovian fear conditioning procedure in which cued and non-cued threats (i.e., unconditioned stimuli) were presented during functional magnetic resonance imaging. Violence exposure was previously assessed at four separate time points when participants were 11-19 years of age. Significant threat type (cued versus non-cued) × sex and sex × violence exposure interactions were observed. Specifically, women and men differed in amygdala and parahippocampal gyrus reactivity to cued versus non-cued threat. Further, dorsolateral PFC (dlPFC) and inferior parietal lobule (IPL) reactivity to threat varied positively with violence exposure among women, but not men. Similarly, threat-elicited skin conductance responses varied positively with violence exposure among women. Finally, women reported greater depression and anxiety symptoms than men. These findings suggest that sex differences in threat-related brain and psychophysiological activity may have implications for mental health

The Journal of Microelectronic Research 2009

https://scholarworks.rit.edu/meec_archive/1017/thumbnail.jp

Telbivudine versus lamivudine in patients with chronic hepatitis B

BACKGROUND: Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B. METHODS: In this double-blind, phase 3 trial, 1370 patients with chronic hepatitis B were randomly assigned to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy end point was noninferiority of telbivudine to lamivudine for therapeutic response (i.e., a reduction in serum HBV DNA levels to fewer than 5 log 10 copies per milliliter, along with loss of hepatitis B e antigen [HBeAg] or normalization of alanine aminotransferase levels). Secondary efficacy measures included histologic response, changes in serum HBV DNA levels, and HBeAg responses. RESULTS: At week 52, a significantly higher proportion of HBeAg-positive patients receiving telbivudine than of those receiving lamivudine had a therapeutic response (75.3% vs. 67.0%, P = 0.005) or a histologic response (64.7% vs. 56.3%, P = 0.01); telbivudine also was not inferior to lamivudine for these end points in HBeAg-negative patients. In HBeAg-positive and HBeAg-negative patients, telbivudine was superior to lamivudine with respect to the mean reduction in the number of copies of HBV DNA from baseline, the proportion of patients with a reduction in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of resistance to the drug. Elevated creatine kinase levels were more common in patients who received telbivudine, whereas elevated alanine aminotransferase and aspartate aminotransferase levels were more common in those who received lamivudine. CONCLUSIONS: Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine. (ClinicalTrials.gov number, NCT00057265.) Copyright © 2007 Massachusetts Medical Society.published_or_final_versio

Significance of Facet Fluid Index in Anterior Cervical Degenerative Spondylolisthesis

STUDY DESIGN: Retrospective cohort study. PURPOSE: To correlate cervical facet fluid characteristics to radiographic spondylolisthesis, determine if facet fluid is associated with instability in cervical degenerative spondylolisthesis, and examine whether vertebral levels with certain facet fluid characteristics and spondylolisthesis are more likely to be operated on. OVERVIEW OF LITERATURE: The relationship between facet fluid and lumbar spondylolisthesis is well-documented; however, there is a paucity of literature investigating facet fluid in degenerative cervical spondylolisthesis. METHODS: Patients diagnosed with cervical degenerative spondylolisthesis were identified from a hospital\u27s medical records. Demographic and surgical characteristics were collected through a structured query language search and manual chart review. Radiographic measurements were made on preoperative MRIs for all vertebral levels diagnosed with spondylolisthesis and adjacent undiagnosed levels between C3 and C6. The facet fluid index was calculated by dividing the facet fluid measurement by the width of the facet. Bivariate analysis was conducted to compare facet characteristics based on radiographic spondylolisthesis and spondylolisthesis stability. RESULTS: We included 154 patients, for whom 149 levels were classified as having spondylolisthesis and 206 levels did not. The average facet fluid index was significantly higher in patients with spondylolisthesis (0.26±0.07 vs. 0.23±0.08, p CONCLUSIONS: Facet fluid index is associated with cervical spondylolisthesis and an increased facet size and fluid width are associated with unstable spondylolisthesis. While cervical spondylolisthesis continues to be an inconclusive finding, vertebral levels with spondylolisthesis, especially the unstable ones, were more likely to be included in the fusion procedure than those without spondylolisthesis

How 'dynasty' became a modern global concept : intellectual histories of sovereignty and property

The modern concept of ‘dynasty’ is a politically-motivated modern intellectual invention. For many advocates of a strong sovereign nation-state across the nineteenth and early twentieth century, in France, Germany, and Japan, the concept helped in visualizing the nation-state as a primordial entity sealed by the continuity of birth and blood, indeed by the perpetuity of sovereignty. Hegel’s references to ‘dynasty’, read with Marx’s critique, further show how ‘dynasty’ encoded the intersection of sovereignty and big property, indeed the coming into self-consciousness of their mutual identification-in-difference in the age of capitalism. Imaginaries about ‘dynasty’ also connected national sovereignty with patriarchal authority. European colonialism helped globalize the concept in the non-European world; British India offers an exemplar of ensuing debates. The globalization of the abstraction of ‘dynasty’ was ultimately bound to the globalization of capitalist-colonial infrastructures of production, circulation, violence, and exploitation. Simultaneously, colonized actors, like Indian peasant/‘tribal’ populations, brought to play alternate precolonial Indian-origin concepts of collective regality, expressed through terms like ‘rajavamshi’ and ‘Kshatriya’. These concepts nourished new forms of democracy in modern India. Global intellectual histories can thus expand political thought today by provincializing and deconstructing Eurocentric political vocabularies and by recuperating subaltern models of collective and polyarchic power.PostprintPeer reviewe

Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Background Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P Conclusion Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.Peer reviewe

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM)