Hmga2 is dispensable for pancreatic cancer development, metastasis, and therapy resistance.

Expression of the chromatin-associated protein HMGA2 correlates with progression, metastasis and therapy resistance in pancreatic ductal adenocarcinoma (PDAC). Hmga2 has also been identified as a marker of a transient subpopulation of PDAC cells that has increased metastatic ability. Here, we characterize the requirement for Hmga2 during growth, dissemination, and metastasis of PDAC in vivo using conditional inactivation of Hmga2 in well-established autochthonous mouse models of PDAC. Overall survival, primary tumour burden, presence of disseminated tumour cells in the peritoneal cavity or circulating tumour cells in the blood, and presence and number of metastases were not significantly different between mice with Hmga2-wildtype or Hmga2-deficient tumours. Treatment of mice with Hmga2-wildtype and Hmga2-deficient tumours with gemcitabine did not uncover a significant impact of Hmga2-deficiency on gemcitabine sensitivity. Hmga1 and Hmga2 overlap in their expression in both human and murine PDAC, however knockdown of Hmga1 in Hmga2-deficient cancer cells also did not decrease metastatic ability. Thus, Hmga2 remains a prognostic marker which identifies a metastatic cancer cell state in primary PDAC, however Hmga2 has limited if any direct functional impact on PDAC progression and therapy resistance

Psychosocial Stress and Cervical Neoplasia Risk

OBJECTIVE: We assessed the association between psychosocial stress and preinvasive cervical neoplasia development controlling for HR-HPV infection. METHODS: This case-control study enrolled low-income women receiving family planning services at health department clinics. There were 59 cases with biopsy confirmed HSIL and 163 with low-grade SIL and 160 controls with normal cervical cytology. A modified SLE scale was used to measure stressful events and the perceived impact of the event in the prior 5 years. Unconditional logistic regression was used to assess SIL risk and stressful events scores and by subscales. RESULTS: After adjusting for age, HR-HPV infection, and lifetime number of sex partners, the SLE count score was associated with an increased risk of SIL among white women (aOR = 1.20; 95% CI = 1.04, 1.38) yet not among African American women (aOR = 1.02; 95% CI = 0.87, 1.19). The relationship stress subscale (divorce, infidelity, an increase in the number of arguments, and psychological and physical partner violence) was the only one of four subscales (loss, violence, and financial stress) associated with SIL, again, only among white women (aOR = 1.54; 95% CI = 1.21, 1.96). CONCLUSIONS: These data suggest that psychosocial stress may play a role in SIL development. Future studies are needed to confirm these findings, to explore racial difference in reporting stress, and to explore the mechanism through which psychosocial stress may affect cervical neoplasia risk

Honeybee linguistics—a comparative analysis of the waggle dance among species of Apis

All honeybees use the waggle dance to recruit nestmates. Studies on the dance precision of Apis mellifera have shown that the dance is often imprecise. Two hypotheses have been put forward aimed at explaining this imprecision. The first argues that imprecision in the context of foraging is adaptive as it ensures that the dance advertises the same patch size irrespective of distance. The second argues that the bees are constrained in their ability to be more precise, especially when the source is nearby. Recent studies have found support for the latter hypothesis but not for the “tuned-error” hypothesis, as the adaptive hypothesis became known. Here we investigate intra-dance variation among Apis species. We analyse the dance precision of A. florea, A. dorsata, and A. mellifera in the context of foraging and swarming. A. mellifera performs forage dances in the dark, using gravity as point of reference, and in the light when dancing for nest sites, using the sun as point of reference. Both A. dorsata and A. florea are open-nesting species; they do not use a different point of reference depending on context. A. florea differs from both A. mellifera and A. dorsata in that it dances on a horizontal surface and does not use gravity but instead “points” directly toward the goal when indicating direction. Previous work on A. mellifera has suggested that differences in dance orientation and point of reference can affect dance precision. We find that all three species improve dance precision with increasing waggle phase duration, irrespective of differences in dance orientation, and point of reference. When dancing for sources nearby, dances are highly variable. When the distance increases, dance precision converges. The exception is dances performed by A. mellifera on swarms. Here, dance precision decreases as the distance increases. We also show that the size of the patch advertised increases with increasing distance, contrary to what is predicted under the tuned-error hypothesis

Is the incidence of invasive vulvar cancer increasing in the United States?

OBJECTIVE: To document incidence rates of vulvar cancer, specifically invasive vulvar cancer, from 1973 to 2004 in the United States. METHODS: Nine US cancer registries from the Surveillance, Epidemiology, and End Results (SEER) databases were used to identify women aged 15-84 years, who were first diagnosed with vulvar cancer during 1973-2004. Age-adjusted incidence rates and annual percentage changes were calculated for different time periods, stage of the disease, age, race, and geographic area. RESULTS: During 1973-2004, the incidence of in situ vulvar tumors increased by an average of 3.5% per year (95% CI: 2.9%, 4.1%), while the incidence of invasive tumors increased 1.0% per year (95% CI: 0.6%, 1.4%). An increasing incidence was observed for localized and regional invasive tumors. To at least some degree, the rise of incidence rates of incidence tumors was evident in every age category, race, and geographic region. CONCLUSIONS: Incidence rates of invasive vulvar cancer have increased in the United States during the last three decades. The reasons for this increase are unknown

Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk

Variation in human major histocompatibility genes may influence the risk of squamous cell cervical cancer (SCC) by altering the efficiency of the T-cell–mediated immune response to human papillomavirus (HPV) antigens. We used high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are codominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at >5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% confidence interval, 3.0–33.3). Among the six combinations that conferred a decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3–0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T-cell responses are both important cofactors with HPV in cervical cancer etiology and indicate that co-occurring HLA alleles across loci seem to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies

Cervical and Vulvar Cancer Risk in Relation to the Joint Effects of Cigarette Smoking and Genetic Variation in Interleukin 2.

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1790-9)

Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study

Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and Umeå, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of Umeå University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD

Effectiveness of an Intervention to Increase Construction Workers' Use of Hearing Protection

In this project we tested the effectiveness of a theory-based intervention (video, pamphlets, and guided practice session) to increase the use of hearing protection devices (HPDs) among Midwestern construction workers and a national group of plumber/pipefitter trainers. Posttest measures were collected 10--12 months following this intervention. Pender's Health Promotion Model (1987) provided the conceptual basis for development of the training program. A total of 837 highnoise- exposed workers were included in the analysis: 652 regional Midwestern construction workers and 185 national plumber/pipefitter trainers. Effectiveness of the intervention was determined through the sequence of analyses recommended by Braver and Braver (1988) for the Solomon Four-Group Design. Analysis of variance and covariance of postintervention use and intention to use HPDs and a meta-analytic test were done. These analyses indicated that the intervention significantly increased use of HPDs but had no effect on intention to use HPDs in the future. Pretesting had no effect on use. Actual or potential applications of this research include guidance in the development of successful theorybased interventions to increase use of HPDs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68025/2/10.1518_001872099779610969.pd