The proapoptotic Bcl-2 family member Bim plays a central role during the development of virus-induced hepatitis

The proapoptotic Bcl-2 homolog Bim was shown to control the apoptosis of both T cells and hepatocytes. This dual role of Bim might be particularly relevant for the development of viral hepatitis, in which both the sensitivity of hepatocytes to apoptosis stimuli and the persistence of cytotoxic T cells are essential factors for the outcome of the disease. The relevance of Bim in regulating survival of cytotoxic T cells or induction of hepatocyte death has only been investigated in separate systems, and their relative contributions to the pathogenesis of T cell-mediated hepatitis remain unclear. Using the highly dynamic model system of lymphocytic choriomeningitis virus-mediated hepatitis and bone marrow chimeras, we found that Bim has a dual role in the development of lymphocytic choriomeningitis virus-induced, T cell-mediated hepatitis. Although the absence of Bim in parenchymal cells led to markedly attenuated liver damage, loss of Bim in the lymphoid compartment moderately enhanced hepatitis. However, when both effects were combined in Bim(-/-) mice, the effect of Bim deficiency in the lymphoid compartment was overcompensated for by the reduced sensitivity of Bim(-/-) hepatocytes to T cell-induced apoptosis, resulting in the protection of Bim(-/-) mice from hepatitis.

Coping With a Family Member's Death: Parenting, Religiosity, and Parent-Child Communication

The present study had three major aims. First, this study was a basic descriptive exploration of the frequency and nature of parent-child communication about death. Second, this study conducted a quantitative analysis to identify predictors of communication and bereaved children¿s emotional and behavioral problems. Third, this study was also a qualitative analysis of parents¿ descriptions of how religious views shape conversations about death and how conversations are beneficial. Based on prior research, it was predicted that positive child outcomes would be associated with parental warmth, religiosity, adaptive coping, positive religious coping, and frequent parent-child communication about death. Conversely, it was predicted that negative child outcomes would be associated with parental psychological control, maladaptive coping, negative religious coping, and less frequent parent-child communication about death. Additionally, it was hypothesized that parents¿ religious and spiritual views would shape parent-child communication about death, and parents would describe numerous benefits of discussing death with children. Parents completed a series of survey measures assessing their religiosity, coping strategies, parent-child communication about death, and their children¿s emotional and behavioral symptoms. Almost 80% of parent-child dyads discussed death at least once a week, and children initiated approximately half of these conversations. Parent-child communication about death was predicted by parents¿ warmth toward and acceptance of their children and inversely predicted by children¿s hyperactivity and social problem solving. Higher levels of children¿s social problem solving could predict lower frequency of parent-child communication about death if children were holding frequent, meaningful, and comforting conversations with friends and other adults. Higher levels of parents¿ psychological control predicted more emotional and behavioral problems in the child. Parents¿ adaptive coping had significant relationships with all of the dimensions of parent-child communication about death. Qualitative analyses revealed that parents perceived their religious beliefs as shaping conversations about death and grief as an individualized journey. A majority of parents described the emotional, social, and intellectual benefits of holding parent-child conversations about death. This study contributes to the literature by further describing parent-child communication about death, identifying its predictors, and investigating parents¿ religiosity and coping strategies in relation to child well-being. Overall, this study revealed the importance of assessing global parenting characteristics (i.e., warmth/acceptance and psychological control) when examining parent-child relationships and communication about death. Furthermore, this unique study illustrates the value of qualitative data when examining parent-child communication about death and religiosity.

A NOVEL AND SIMPLE RULE OF THUMB FOR MULTIPLICITY CONTROL IN EQUIVALENCE TESTING USING TWO ONE-SIDED TESTS

Equivalence testing is growing in use in scientific research outside of its traditional role in the drug approval process. Largely due to its ease of use and recommendation from the United States Food and Drug Administration guidance, the most common statistical method for testing (bio)equivalence is the two one-sided tests procedure (TOST). Like classical point-null hypothesis testing, TOST is subject to multiplicity concerns as more comparisons are made. In this manuscript, a condition that bounds the family-wise error rate (FWER) using TOST is given. This condition then leads to a simple solution for controlling the FWER. Specifically, we demonstrate that if all pairwise comparisons of k independent groups are being evaluated for equivalence, then simply scaling the nominal Type I error rate down by (k - 1) is sufficient to maintain the family-wise error rate at the desired value or less. The resulting rule is much less conservative than the equally simple Bonferroni correction. An example of equivalence testing in a non drug-development setting is given.

Genetic association studies under the population stratification, family pedigree and application to genome-wide association studies

This dissertation has three separate parts: the first part deals with the general pedigree association testing incorporating continuous covariates; the second part deals with the association tests under population stratification using the conditional likelihood tests; the third part deals with the genome-wide association studies based on the real rheumatoid arthritis (RA) disease data sets from Genetic Analysis Workshop 16 (GAW16) problem 1. Many statistical tests are developed to test the linkage and association using either case-control status or phenotype covariates for family data structure, separately. Those univariate analyses might not use all the information coming from the family members in practical studies. On the other hand, the human complex disease do not have a clear inheritance pattern, there might exist the gene interactions or act independently. In part I, the new proposed approach MPDT is focused on how to use both the case control information as well as the phenotype covariates. This approach can be applied to detect multiple marker effects. Based on the two existing popular statistics in family studies for case-control and quantitative traits respectively, the new approach could be used in the simple family structure data set as well as general pedigree structure. The combined statistics are calculated using the two statistics; A permutation procedure is applied for assessing the p-value with adjustment from the Bonferroni for the multiple markers. We use simulation studies to evaluate the type I error rates and the powers of the proposed approach. Our results show that the combined test using both case-control information and phenotype covariates not only has the correct type I error rates but also is more powerful than the other existing methods. For multiple marker interactions, our proposed method is also very powerful. Selective genotyping is an economical strategy in detecting and mapping quantitative trait loci in the genetic dissection of complex disease. When the samples arise from different ethnic groups or an admixture population, all the existing selective genotyping methods may result in spurious association due to different ancestry distributions. The problem can be more serious when the sample size is large, a general requirement to obtain sufficient power to detect modest genetic effects for most complex traits. In part II, I describe a useful strategy in selective genotyping while population stratification is present. Our procedure used a principal component based approach to eliminate any effect of population stratification. The paper evaluates the performance of our procedure using both simulated data from an early study data sets and also the HapMap data sets in a variety of population admixture models generated from empirical data. There are one binary trait and two continuous traits in the rheumatoid arthritis dataset of Problem 1 in the Genetic Analysis Workshop 16 (GAW16): RA status, AntiCCP and IgM. To allow multiple traits, we suggest a set of SNP-level F statistics by the concept of multiple-correlation to measure the genetic association between multiple trait values and SNP-specific genotypic scores and obtain their null distributions. Hereby, we perform 6 genome-wide association analyses using the novel one- and two-stage approaches which are based on single, double and triple traits. Incorporating all these 6 analyses, we successfully validate the SNPs which have been identified to be responsible for rheumatoid arthritis in the literature and detect more disease susceptibility SNPs for follow-up studies in the future. Except for chromosome 13 and 18, each of the others is found to harbour susceptible genetic regions for rheumatoid arthritis or related diseases, i.e., lupus erythematosus. This topic is discussed in part III.

A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001-2004

BACKGROUND: In 2001, the observed annual mortality from Creutzfeldt-Jakob disease (CJD) in Switzerland increased from less than 1.5 to 2.6 per million inhabitants. An underlying cause could not be identified. METHODS: To analyse potential risk factors for sCJD in Switzerland, close relatives of 69 sCJD-patients and 224 frequency age-matched controls were interviewed in a case-control study using a standardised questionnaire. 135 potential risk factors including socio-demographics, medical history, occupation and diet were analysed by logistic regression adjusting for age, sex and education. RESULTS: sCJD patients were more likely to have travelled abroad, worked at an animal laboratory, undergone invasive dental treatment, orthopaedic surgery, ophthalmologic surgery after 1980, regular GP visits, taken medication regularly, and consumed kidney. No differences between patients and controls were found for residency, family history, and exposure to environmental and other dietary factors. CONCLUSION: Although some factors were significantly more frequent among sCJD-cases, this study did not reveal specific explanations for the increased incidence of deaths due to sporadic CJD observed in Switzerland since 2001. Results have to be interpreted with caution due to multiple testing and possible recall bias in association with a long incubation period. The most plausible reason for the increase in Swiss sCJD cases after 2000 is an improved case ascertainment. Therefore, underreporting of cases might well have occurred before the year 2001, and the "real" yearly incidence of sCJD might not be lower than, but rather above 2 per million inhabitants.

Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes

BACKGROUND: Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance. OBJECTIVE: The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders. DESIGN: Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g x kg FFM(-1) x d(-1), +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU x kg(-1) x min(-1)), together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by 1H-magnetic resonance spectroscopy. RESULTS: The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (-27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group x diet interaction: P < 0.05). CONCLUSIONS: A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes. This trial was registered at clinicaltrials.gov as NCT00523562.

Differential association of MUC5AC and CLCA1 expression in small cartilaginous airways of RAO-affected and control horses

REASONS FOR PERFORMING STUDY: Airway mucus accumulation is associated with indoor irritant and allergen exposure in horses with recurrent airway obstruction (RAO). Epidermal growth factor receptor (EGFR) and a chloride channel (calcium activated, family member 1; CLCA1) are key signalling molecules involved in mucin gene expression. OBJECTIVES: We hypothesised that exposure to irritants and aeroallergens would lead to increased expression of the mucin gene eqMUC5AC and increased stored mucosubstance in the airways of RAO-affected horses, associated with increased neutrophils and CLCA1 and EGFR mRNA levels. METHODS: We performed quantitative RT-PCR of eqMUC5AC, CLCA1 and EGFR; volume density measurements of intraepithelial mucosubstances; and cytological differentiation of intraluminal inflammatory cells in small cartilaginous airways from cranial left and right and caudal left and right lung lobes of 5 clinically healthy and 5 RAO-affected horses that had been exposed to indoor stable environment for 5 days before euthanasia. RESULTS: Neutrophils were increased in RAO-affected horses compared to clinically healthy controls. EqMUC5AC mRNA levels were positively correlated with both CLCA1 and EGFR mRNA levels in RAO-affected horses but only with CLCA1 in controls. The relationship between eqMUC5AC and CLCA1 differed in the 2 groups of horses with RAO-affected animals overexpressing CLCA1 in relation to eqMUC5AC. CONCLUSIONS: These data implicate CLCA1 as a signalling molecule in the expression of eqMUC5AC in horses but also suggest differential regulation by CLCA1 and EGFR between horses with RAO and those with milder degrees of airway inflammation.

The Bcl-2 Protein Family Member Bok Binds to the Coupling Domain of Inositol 1,4,5-Trisphosphate Receptors and Protects Them from Proteolytic Cleavage

Bok is a member of the Bcl-2 protein family that controls intrinsic apoptosis. Bok is most closely related to the pro-apoptotic proteins Bak and Bax, but in contrast to Bak and Bax, very little is known about its cellular role. Here we report that Bok binds strongly and constitutively to inositol 1,4,5-trisphosphate receptors (IP3Rs), proteins that form tetrameric calcium channels in the endoplasmic reticulum (ER) membrane and govern the release of ER calcium stores. Bok binds most strongly to IP3R1 and IP3R2, and barely to IP3R3, and essentially all cellular Bok is IP3R bound in cells that express substantial amounts of IP3Rs. Binding to IP3Rs appears to be mediated by the putative BH4 domain of Bok and the docking site localizes to a small region within the coupling domain of IP3Rs (amino acids 1895–1903 of IP3R1) that is adjacent to numerous regulatory sites, including sites for proteolysis. With regard to the possible role of Bok-IP3R binding, the following was observed: (i) Bok does not appear to control the ability of IP3Rs to release ER calcium stores, (ii) Bok regulates IP3R expression, (iii) persistent activation of inositol 1,4,5-trisphosphate-dependent cell signaling causes Bok degradation by the ubiquitin-proteasome pathway, in a manner that parallels IP3R degradation, and (iv) Bok protects IP3Rs from proteolysis, either by chymotrypsin in vitro or by caspase-3 in vivo during apoptosis. Overall, these data show that Bok binds strongly and constitutively to IP3Rs and that the most significant consequence of this binding appears to be protection of IP3Rs from proteolysis. Thus, Bok may govern IP3R cleavage and activity during apoptosis.

Critical Control Points for Profitability in the Cow-Calf Enterprise

Financial, economic, and biological data collected from cow-calf producers who participated in the Illinois and Iowa Standardized Performance Analysis (SPA) programs were used in this study. Data used were collected for the 1996 through 1999 calendar years, with each herd within year representing one observation. This resulted in a final database of 225 observations (117 from Iowa and 108 from Illinois) from commercial herds with a range in size from 20 to 373 cows. Two analyses were conducted, one utilizing financial cost of production data, the other economic cost of production data. Each observation was analyzed as the difference from the mean for that given year. The independent variable utilized in both the financial and economic models as an indicator of profit was return to unpaid labor and management per cow (RLM). Used as dependent variables were the five factors that make up total annual cow cost: feed cost, operating cost, depreciation cost, capital charge, and hired labor, all on an annual cost per cow basis. In the economic analysis, family labor was also included. Production factors evaluated as dependent variables in both models were calf weight, calf price, cull weight, cull price, weaning percentage, and calving distribution. Herd size and investment were also analyzed. All financial factors analyzed were significantly correlated to RLM (P < .10) except cull weight, and cull price. All economic factors analyzed were significantly correlated to RLM (P < .10) except calf weight, cull weight and cull price. Results of the financial prediction equation indicate that there are eight measurements capable of explaining over 82 percent of the farm-to-farm variation in RLM. Feed cost is the overriding factor driving RLM in both the financial and economic stepwise regression analyses. In both analyses over 50 percent of the herd-to-herd variation in RLM could be explained by feed cost. Financial feed cost is correlated (P < .001) to operating cost, depreciation cost, and investment. Economic feed cost is correlated (P < .001) with investment and operating cost, as well as capital charge. Operating cost, depreciation, and capital charge were all negatively correlated (P < .10) to herd size, and positively correlated (P < .01) to feed cost in both analyses. Operating costs were positively correlated with capital charge and investment (P < .01) in both analyses. In the financial regression model, depreciation cost was the second critical factor explaining almost 9 percent of the herd-to-herd variation in RLM followed by operating cost (5 percent). Calf weight had a greater impact than calf price on RLM in both the financial and economic regression models. Calf weight was the fourth indicator of RLM in the financial model and was similar in magnitude to operating cost. Investment was not a significant variable in either regression model; however, it was highly correlated to a number of the significant cost variables including feed cost, depreciation cost, and operating cost (P < .001, financial; P < .10, economic). Cost factors were far more influential in driving RLM than production, reproduction, or producer controlled marketing factors. Of these cost factors, feed cost had by far the largest impact. As producers focus attention on factors that affect the profitability of the operation, feed cost is the most critical control point because it was responsible for over 50 percent of the herd-to-herd variation in profit.

One size does not fit all: Entrepreneurial families’ reliance on family offices

Family offices are organisations dedicated to the management of entrepreneurial families’ private wealth. Based on agency theory, we analyse types of family offices with regard to the families’ goals and the control mechanisms used to ensure goal achievement. Family-dominant management and private client structures involve stronger emphasis on non-financial goals in single and multi-family offices than in non-family-dominant management and open client structures. Variations in family involvement, ranging from family dominance to the complete absence of family ownership and/or management, and diverse client structures justify the differential reliance on formal and informal control mechanisms.

Development of Values after Compulsory School: Work comes first, then family

During school-to-work transition, adolescents develop values and prioritize what is im-portant in their life. Values are concepts or beliefs about desirable states or behaviors that guide the selection or evaluation of behavior and events, and are ordered by their relative importance (Schwartz & Bilsky, 1987). Stressing the important role of values, career re-search has intensively studied the effect of values on educational decisions and early career development (e.g. Eccles, 2005; Hirschi, 2010; Rimann, Udris, & Weiss, 2000). Few re-searchers, however, have investigated so far how values develop in the early career phase and how value trajectories are influenced by individual characteristics. Values can be oriented towards specific life domains, such as work or family. Work values include intrinsic and extrinsic aspects of work (e.g., self-development, cooperation with others, income) (George & Jones, 1997). Family values include the importance of partner-ship, the creation of an own family and having children (Mayer, Kuramschew, & Trommsdroff, 2009). Research indicates that work values change considerably during early career development (Johnson, 2001; Lindsay & Knox, 1984). Individual differences in work values and value trajectories are found e.g., in relation to gender (Duffy & Sedlacek, 2007), parental background (Loughlin & Barling, 2001), personality (Lowry et al., 2012), educa-tion (Battle, 2003), and the anticipated timing of school-to-work transition (Porfeli, 2007). In contrast to work values, research on family value trajectories is rare and knowledge about the development during the school-to-work transition and early career development is lack-ing. This paper aims at filling this research gap. Focusing on family values and intrinsic work values and we expect a) family and work val-ues to change between ages 16 and 25, and b) that initial levels of family and work values as well as value change to be predicted by gender, reading literacy, ambition, and expected du-ration of education. Method. Using data from 2620 young adults (59.5% females), who participated in the Swiss longitudinal study TREE, latent growth modeling was employed to estimate the initial level and growth rate per year for work and family values. Analyses are based on TREE-waves 1 (year 2001, first year after compulsory school) to 8 (year 2010). Variables in the models included family values and intrinsic work values, gender, reading literacy, ambition and ex-pected duration of education. Language region was included as control variable. Results. Family values did not change significantly over the first four years after leaving compulsory school (mean slope = -.03, p =.36). They increased, however, significantly five years after compulsory school (mean slope = .13, p >.001). Intercept (.23, p < .001), first slope (.02, p < .001), and second slope (.01, p < .001) showed significant variance. Initial levels were higher for men and those with higher ambitions. Increases were found to be steeper for males as well as for participants with lower educational duration expectations and reading skills. Intrinsic work values increased over the first four years (mean slope =.03, p <.05) and showed a tendency to decrease in the years five to ten (mean slope = -.01, p < .10). Intercept (.21, p < .001), first slope (.01, p < .001), and second slope (.01, p < .001) showed signifi-cant variance, meaning that there are individual differences in initial levels and growth rates. Initial levels were higher for females, and those with higher ambitions, expecting longer educational pathways, and having lower reading skills. Growth rates were lower for the first phase and steeper for the second phase for males compared to females. Discussion. In general, results showed different patterns of work and family value trajecto-ries, and different individual factors related to initial levels and development after compul-sory school. Developments seem to fit to major life and career roles: in the first years after compulsory school young adults may be engaged to become established in one's job; later on, raising a family becomes more important. That we found significant gender differences in work and family trajectories may reflect attempts to overcome traditional roles, as over-all, women increase in work values and men increase in family values, resulting in an over-all trend to converge.

Bovine viral diarrhea (BVD): from biology to control

Bovine viral diarrhea virus (BVDV) is endemic worldwide. Together with classical swine fever and border disease viruses, it belongs to the genus Pestivirus of the family Flaviviridae. Most infections with BVDV take a transient, acute, course. Only rarely BVDV persists in its hosts. Due to the early time point of infection in utero, persistently infected (PI) animals are immunotolerant to the infecting non-cytopathic BVDV. In such animals the virus may mutate to a cytopathic biotype, causing lethal mucosal disease. In BVD-endemic regions, approximately 1% of the animals are PI. Removal of all PI animals leads to extinction of BVD. This approach to BVD eradication has been vindicated in Scandinavia. Following the same principles, regional and country-wide eradication programs are run in different parts of the world. These programs differ in the way PI animals are detected and in the role of vaccines. The Scandinavian two-step method of detecting PI animals is based on (i) the high level of seroprevalence in herds where PI animals are present and (ii) on testing all animals for virus in such herds. However, the high average herd seroprevalence in Switzerland made it impossible to define a reasonable threshold for virus testing. Therefore, all animals were directly tested for virus in the year 2008 and all newborn calves until the end of 2012, when the PI prevalence had dropped to 0.02%. Vaccination remains prohibited. Since 2013, surveillance for BVD is accomplished by serology. As a unique consequence of eradication, over 7500 viral strains are available to us for genetic studies.

MULTIPLE POSTTRANSCRIPTIONAL REGULATORY FEATURES CONTROL EXPRESSION OF ETHANOLAMINE UTILIZATION GENES IN ENTEROCOCCUS FAECALIS

Enterococcus faecalis is a Gram-positive bacterium that lives as a commensal organism in the mammalian gastrointestinal tract, but can behave as an opportunistic pathogen. Our lab discovered that mutation of the eutK gene attenuates virulence of E. faecalis in the C. elegans model host. eutK is part of the ethanolamine metabolic pathway which was previously unknown in E. faecalis. I discovered the presence of two unique posttranscriptional regulatory features that control expression of eut locus genes. The first feature I found is an AdoCBL riboswitch, a cis-acting RNA regulatory element that acts as a positive regulator of gene expression. The second feature I discovered is a unique two-component system, EutVW. The EutV response regulator contains an ANTAR family domain, which binds RNA to trigger transcriptional antitermination. I determined that induction of expression of several genes in the eut locus is dependent on ethanolamine, AdoCBL and the two-component system. AdoCBL and ethanolamine are both required for induction of eut locus gene expression. Additionally, I discovered eutG is regulated by a unique mechanism of antitermination. Both the AdoCBL riboswitch and EutV response regulator control the expression of the downstream gene eutG. EutV potentially acts through a novel antitermination mechanism in which a dimer of EutV binds to a pair of mRNA stem loops forming an antitermination complex. My data show a unique mechanism by which two environmental signals are integrated by two different posttranscriptional regulators to regulate a single locus.

Does Immediate Access to Birth Control Help Prevent Pregnancy? A Comparison of Onsite Provision Versus Off Campus Referral for Contraception at Two School-Based Clinics

PURPOSE: The purpose of this study was to assess the impact of different policies on access to hormonal contraception and pregnancy rates at two high school-based clinics. METHODS: Two clinics in high schools (Schools A and B), located in a large urban district in the southwest US, provide primary medical care to enrolled students with parental consent; the majority of whom have no health insurance coverage. The hormonal contraceptive dispensing policy of at School clinic A involves providing barrier, hormonal and emergency contraceptive services on site. School clinic B uses a referral policy that directs students to obtain contraception at an off-campus affiliated family planning clinic. Baseline data (age, race and history of prior pregnancy) on female students seeking hormonal contraception at the two clinics between 9/2008-12/2009 were extracted from an electronic administrative database (AHLERS Integrated System). Data on birth control use and pregnancy tests for each student was then tracked electronically through 3/31/2010. The outcomes measures were accessing hormonal contraception and positive pregnancy tests at any point during or after birth control use were started through 12/2009. The appointment keeping rate for contraceptive services and the overall pregnancy rates were compared between the two schools. In addition the pregnancy rates were compared between the two schools for students with and without a prior history of pregnancy. RESULTS: School clinic A: 79 students sought hormonal contraception; mean age 17.5 years; 68% were > 18 years; 77% were Hispanic; and 20% reported prior pregnancy. The mean duration of the observation period was 13 months (4-19 months). All 79 students received hormonal contraception (65% pill and 35% long acting progestin injection) onsite. During the observation period, the overall pregnancy rate was 6% (5/79); 4.7% (3/63) among students with no prior pregnancy. School clinic B: 40 students sought hormonal contraception; mean age 17.5 years; 52% > 18 years; 88 % were Hispanic; and 7.5% reported prior pregnancy. All 40 students were referred to the affiliated clinic. The mean duration of the observation period was 11.9 months (4-19 months). 50% (20) kept their appointment. Pills were dispensed to 85% (17/20) and 15% (3/20) received long acting progestin injection. The overall pregnancy rate was 20% (8/40); 21.6% (8/37) among students with no prior pregnancy. A significantly higher frequency of students seeking hormonal contraception kept their initial appointment for birth control at the school dispensing onsite contraception compared to the school with a referral policy for contraception (p<0.05). The pregnancy rate was significantly higher for the school with a referral policy for contraception compared to the school with onsite contraceptive services (p< 0.05). The pregnancy rate was also significantly higher for students without a prior history of pregnancy in the school with a referral policy for contraception (21.6%) versus the school with onsite contraceptive services (4.7%) (p< 0.05). CONCLUSION: This preliminary study showed that School clinic B with a referral policy had a lower appointment keeping rate for contraceptive services and a higher pregnancy rate than School clinic A with on-site contraceptive services. An on-site dispensing policy for hormonal contraceptives at high school-based health clinics may be a convenient and effective approach to prevent unintended first and repeat pregnancies among adolescents who seek hormonal contraception. This study has strong implications for reproductive health policy, especially as directed toward high-risk teenage populations.

A case-control study of hepatitis C virus and its interaction with hepatitis B virus on the development of hepatocellular carcinoma in the USA

Objective. The aim of this study was to assess the independent risk of hepatitis C virus (HCV) infection in the development of hepatocellular carcinoma (HCC). The independent risk of hepatitis B virus (HBV), its interaction with hepatitis C virus and the association with other risk factors were examined.^ Methods. A hospital-based case-control study was conducted between January 1994 and December 1995. We enrolled 115 pathologically confirmed HCC patients and 230 nonliver cancer controls, who were matched by age ($\pm$5 years), gender, and year of diagnosis. Both cases and controls were recruited from The University of Texas M. D. Anderson Cancer Center at Houston. The risk factors were collected through personal interviews and blood samples were tested for HCV and HBV markers. Univariate and multivariate analyses were performed through conditional logistic regression.^ The prevalence of anti-HCV positive is 25.2% in HCC cases compared to 3.0% in controls. The univariate analysis showed that anti-HCV, HBsAg, alcohol drinking and cigarette smoking were significantly associated with HCC, however, family history of cancer, occupational chemical exposure, and use of oral contraceptive were not. Multivariate analysis revealed a matched odds ratio (OR) of 10.1 (95% CI 3.7-27.4) for anti-HCV, and an OR of 11.9 (95% CI 2.5-57.5) for HBsAg. However, dual infection of HCV and HBV had only a thirteen times increase in the risk of HCC, OR = 13.9 (95% CI 1.3-150.6). The estimated population attributable risk percent was 23.4% for HCV, 12.6% for HBV, and 5.3% for both viruses. Ever alcohol drinkers was positively associated with HCC, especially among daily drinkers, matched OR was 5.7 (95% CI 2.1-15.6). However, there was no significant increase in the risk of HCC among smokers as compared to nonsmokers. The mean age of HCC patients was significantly younger among the HBV(+) group and among the HCV(+)/HBV(+) group, when compared to the group of HCC patients with no viral markers. The association between past histories of blood transfusion, acupuncture, tattoo and IVDU was highly significant among the HCV(+) group and the HBV(+)/HCV(+) group, as compared to HCC patients with no viral markers. Forty percent of the HCC patients were pathologically or clinically diagnosed with liver cirrhosis. Anti-HCV(+) (OR = 3.6 95% CI 1.5-8.9) and alcohol drinking (OR = 2.7 95% CI 1.1-6.7), but not HBsAg, are the major risk factors for liver cirrhosis in HCC patients.^ Conclusion. Both hepatitis B virus and hepatitis C virus were independent risk factors for HCC. There was not enough evidence to determine the interaction between both viruses. Only daily alcoholic drinkers showed increasing risk for HCC development, as compared to nondrinkers. ^