184 research outputs found

    Hillslope and groundwater contributions to streamflow in a Rocky Mountain watershed underlain by glacial till and fractured sedimentary bedrock

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    Permeable sedimentary bedrock overlain by glacial till leads to large storage capacities and complex subsurface flow pathways in the Canadian Rocky Mountain region. While some inferences on the storage and release of water can be drawn from conceptualizations of runoff generation (e.g., runoff thresholds and hydrologic connectivity) in physically similar watersheds, relatively little research has been conducted in snow-dominated watersheds with multilayered permeable substrates that are characteristic of the Canadian Rocky Mountains. Stream water and source water (rain, snowmelt, soil water, hillslope groundwater, till groundwater, and bedrock groundwater) were sampled in four sub-watersheds (Star West Lower, Star West Upper, Star East Lower, and Star East Upper) in Star Creek, SW Alberta, to characterize the spatial and temporal variation in source water contributions to streamflow in upper and lower reaches of this watershed. Principal component analysis was used to determine the relative dominance and timing of source water contributions to streamflow over the 2014 and 2015 hydrologic seasons. An initial displacement of water stored in the hillslope over winter (reacted water rather than unreacted snowmelt and rainfall) occurred at the onset of snowmelt before stream discharge responded significantly. This was followed by a dilution effect as snowmelt saturated the landscape, recharged groundwater, and connected the hillslopes to the stream. Fall baseflows were dominated by either riparian water or hillslope groundwater in Star West. Conversely, in Star East, the composition of stream water was similar to hillslope water in August but plotted outside the boundary of the measured sources in September and October. The chemical composition of groundwater seeps followed the same temporal trend as stream water, but the consistently cold temperatures of the seeps suggested deep groundwater was likely the source of this late fall streamflow. Temperature and chemical signatures of groundwater seeps also suggest highly complex subsurface flow pathways. The insights gained from this research help improve our understanding of the processes by which water is stored and released from watersheds with multilayered subsurface structures

    DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets

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    <p>Abstract</p> <p>Background</p> <p>The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52) and their <it>in vitro </it>models (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3) by methylation-specific polymerase chain reaction (MSP). Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features.</p> <p>Results</p> <p>Eight out of the 13 genes were hypermethylated among the ovarian carcinomas, and altogether 40 of 52 tumours were methylated in one or more genes. Promoter hypermethylation of <it>HOXA9</it>, <it>RASSF1A</it>, <it>APC</it>, <it>CDH13</it>, <it>HOXB5</it>, <it>SCGB3A1 (HIN-1)</it>, <it>CRABP1</it>, and <it>MLH1 </it>was found in 51% (26/51), 49% (23/47), 24% (12/51), 20% (10/51), 12% (6/52), 10% (5/52), 4% (2/48), and 2% (1/51) of the carcinomas, respectively, whereas <it>ADAMTS1</it>, <it>MGMT</it>, <it>NR3C1</it>, <it>p14</it><sup><it>ARF</it></sup>, and <it>p16</it><sup><it>INK</it>4<it>a </it></sup>were unmethylated in all samples. The methylation frequencies of <it>HOXA9 </it>and <it>SCGB3A1 </it>were higher among relatively early-stage carcinomas (FIGO I-II) than among carcinomas of later stages (FIGO III-IV; <it>P </it>= 0.002, <it>P </it>= 0.020, respectively). The majority of the early-stage carcinomas were of the endometrioid histotype. Additionally, <it>HOXA9 </it>hypermethylation was more common in tumours from patients older than 60 years of age (15/21) than among those of younger age (11/30; <it>P </it>= 0.023). Finally, there was a significant difference in <it>HOXA9 </it>methylation frequency among the histological types (<it>P </it>= 0.007).</p> <p>Conclusion</p> <p>DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis and <it>HOXA9</it>, <it>HOXB5</it>, <it>SCGB3A1</it>, and <it>CRABP1 </it>are identified as novel hypermethylated target genes in this tumour type.</p

    Adolescent substance use and educational attainment: an integrative data analysis comparing cannabis and alcohol from three Australasian cohorts

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    Background: The relative contributions of cannabis and alcohol use to educational outcomes are unclear. We examined the extent to which adolescent cannabis or alcohol use predicts educational attainment in emerging adulthood. Methods: Participant-level data were integrated from three longitudinal studies from Australia and New Zealand (Australian Temperament Project, Christchurch Health and Development Study, and Victorian Adolescent Health Cohort Study). The number of participants varied by analysis (N = 2179–3678) and were assessed on multiple occasions between ages 13 and 25. We described the association between frequency of cannabis or alcohol use prior to age 17 and high school non-completion, university non-enrolment, and degree non-attainment by age 25. Two other measures of alcohol use in adolescence were also examined. Results: After covariate adjustment using a propensity score approach, adolescent cannabis use (weekly+) was associated with 1½ to two-fold increases in the odds of high school non-completion (OR = 1.60, 95% CI = 1.09–2.35), university non-enrolment (OR = 1.51, 95% CI = 1.06–2.13), and degree non-attainment (OR = 1.96, 95% CI = 1.36–2.81). In contrast, adjusted associations for all measures of adolescent alcohol use were inconsistent and weaker. Attributable risk estimates indicated adolescent cannabis use accounted for a greater proportion of the overall rate of non-progression with formal education than adolescent alcohol use. Conclusions: Findings are important to the debate about the relative harms of cannabis and alcohol use. Adolescent cannabis use is a better marker of lower educational attainment than adolescent alcohol use and identifies an important target population for preventive intervention

    Adverse adult consequences of different alcohol use patterns in adolescence: An integrative analysis of data to age 30 years from four Australasian cohorts

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    BACKGROUND AND AIMS: Studies have linked adolescent alcohol use with adverse consequences in adulthood; yet it is unclear how strong the associations are and to what extent they may be due to confounding. Our aim was to estimate the strength of association between different patterns of adolescent drinking and longer-term psychosocial harms taking into account individual, family, and peer factors. DESIGN: Participant-level data were integrated from four long running longitudinal studies: Australian Temperament Project; Christchurch Health and Development Study; Mater Hospital and University of Queensland Study of Pregnancy; Victorian Adolescent Health Cohort Study. SETTING: Australia and New Zealand. PARTICIPANTS: Participants were assessed on multiple occasions between ages 13 and 30 years (from 1991-2012). Number of participants varied (up to N=9453) by analysis. MEASUREMENTS: Three patterns of alcohol use (frequent, heavy episodic, and problem drinking) were assessed prior to age 17. Thirty outcomes were assessed to age 30 spanning substance use and related problems, antisocial behavior, sexual risk-taking, accidents, socioeconomic functioning, mental health, and partner relationships. FINDINGS: After covariate adjustment, weekly drinking prior to age 17 was associated with a two to three-fold increase in the odds of binge drinking (OR: 2.14; 95%CI: 1.57-2.90), drink driving (OR: 2.78; 95%CI: 1.84-4.19), alcohol-related problems (OR: 3.04; 95%CI: 1.90-4.84), and alcohol dependence (OR: 3.30; 95%CI: 1.69-6.47) in adulthood. Frequency of drinking accounted for a greater proportion of the rate of most adverse outcomes than the other measures of alcohol use. Associations between frequent, heavy episodic, and problem drinking in adolescence and most non-alcohol outcomes were largely explained by shared risk factors for adolescent alcohol use and poor psychosocial functioning. CONCLUSIONS: Frequency of adolescent drinking predicts substance use problems in adulthood as much as, and possibly more than, heavy episodic and problem drinking independent of individual, family and peer predictors of those outcomes

    A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

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    Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2–8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA

    PARP-1 Val762Ala Polymorphism Is Associated with Risk of Cervical Carcinoma

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    PARP-1 is a nuclear enzyme that plays an important role in DNA repair, recombination, proliferation and the genome stability. The PARP-1 Val762Ala polymorphism has been associated with increased risk of developing cancers of the prostate, esophagus and lung. The aim of this study was to determine whether the PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma. MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with cervical carcinoma, 480 women with CIN and 800 controls. The genotyping method was confirmed by the DNA sequencing analysis. The PARP-1 Val762Ala polymorphism was not associated with the risk of CIN. However, women carrying the PARP-1 Ala762Ala genotype were significantly susceptible to cervical carcinoma (OR: 2.70, 95% CI: 1.47–3.70), and the similar results were also found in squamous cell carcinoma (OR: 2.56, 95% CI: 1.47–3.70). In HPV positive population, the PARP-1 Ala762Ala genotype was also associated with increased risk of cervical carcinoma (OR: 5.56, 95% CI: 2.08–14.3). Our results indicate that the PARP-1 Ala762Ala genotype increases the risk of cervical carcinoma

    Identification of aberrant forms of alkaline sphingomyelinase (NPP7) associated with human liver tumorigenesis

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    Alkaline sphingomyelinase (alk-SMase) is expressed in the intestine and human liver. It may inhibit colonic tumorigenesis, and loss of function mutations have been identified in human colon cancer. The present study investigates its expression in human liver cancer. In HepG2 liver cancer cells, RT–PCR identified three transcripts with 1.4, 1.2 and 0.4 kb, respectively. The 1.4 kb form is the wild-type cDNA with five translated exons, the 1.2 kb product lacks exon 4 and the 0.4 kb form is a combination of exons 1 and 5. Genomic sequence showed that these aberrant transcripts were products of alternative splicing. Transient expression of the 1.2 kb form showed no alk-SMase activity. In HepG2 cells, the alk-SMase activity is low in monolayer condition and increased with cell polarisation. Coexistence of 1.4 and 1.2 kb forms was also identified in one hepatoma biopsy. GenBank search identified a cDNA clone from human liver tumour, which codes a protein containing full length of alk-SMase plus a 73-amino-acid tag at the N terminus. The aberrant form was translated by an alternative starting codon upstream of the wild-type mRNA. Expression study showed that linking the tag markedly reduced the enzyme activity. We also analysed human liver biopsy samples and found relatively low alk-SMase activity in diseases with increased risk of liver tumorigenesis. In conclusion, expression of alk-SMase is changed in hepatic tumorigenesis, resulting in loss or marked reduction of the enzyme function

    Assessing Perceived Risk and STI Prevention Behavior: A National Population-Based Study with Special Reference to HPV

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    Aim: This thesis aims to provide a multidimensional assessment of infection risks and to evaluate strategies for HPV prevention including vaccination with quadrivalent HPVvaccines, dose-level vaccine effectiveness and condom use in high STI risk situations. Methods: Multiple population-based registers and questionnaire responses provided data for this thesis. Various multivariable and univariate regression models were fit. Findings: Overall, quadrivalent HPV-vaccination was highly effective against genital warts (GW) also referred to as condyloma, which is the first HPV disease endpoint possible to measure. However, effectiveness was contingent upon young age-at-first vaccination, with effectiveness declining steadily the older the age-at-first vaccination. Among women above 20 years of age there was low to immeasurable effectiveness and suggestive evidence vaccinations in this age group tended to reach women at high GW risk. There were marked socioeconomic disparities in the opportunistic (on-demand with co-pay) vaccination strategy evaluated, with women and girls who have parents with the highest education level compared to the lowest having a 15 times greater likelihood to be vaccinated (Study III). Once vaccination was initiated, however, high parental education level was unrelated to vaccination completion. Maximum protection against GW was found among girls vaccinated under the age of 17 who had received three doses of the vaccine. No differences in effectiveness were found for girls who received twodoses between ages 10-16 with that of those who received three-doses between ages 17- 19 (Study IV). GW affects more men than women in Sweden as of 2010 with 453 per 100 000 men and 365 per 100 000 women treated. A decline between 25-30% was seen between 2006 and 2010 among women in the age groups with the highest vaccination coverage. No decline was found amongst men and their GW incidence has steadily increased between 2006 and 2010 (Study II). Reported condom use in high risk situations was low among both men and women, with 41% of men and 34% of women reporting always/almost always condom use with temporary partners. STI risk perception was also low, with approximately 10% of sexually active respondents considering themselves at large risk of contracting an STI. There was no association between men’s condom use and their STI risk perception but there was an association for women (Study I). Conclusions: Results suggest that males bear a substantial burden of HPV-related condyloma where incidence has dropped among women. When planning HPVvaccination among females, efforts should target girls under age 14 for maximum effectiveness. Quadrivalent HPV-vaccination offers most protection against condyloma at three doses. Gross social inequity was found with opportunistic HPV-vaccination. There were large gender differences in factors associated with condom use in high risk situations and STI risk perceptions
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