Background

Although case-control studies have identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer, the clinical role of these SNPs remains unclear.

Objective

Evaluate previously identified SNPs for association with prostate cancer and accuracy in predicting prostate cancer in a large prospective population-based cohort of unscreened men.

Design, setting, and participants

This study used a nested case-control design based on the Malmö Diet and Cancer cohort with 943 men diagnosed with prostate cancer and 2829 matched controls. Blood samples were collected between 1991 and 1996, and follow-up lasted through 2005.

Measurements

We genotyped 50 SNPs, analyzed prostate-specific antigen (PSA) in blood from baseline, and tested for association with prostate cancer using the Cochran-Mantel-Haenszel test. We further developed a predictive model using SNPs nominally significant in univariate analysis and determined its accuracy to predict prostate cancer.

Results and limitations

Eighteen SNPs at 10 independent loci were associated with prostate cancer. Four independent SNPs at four independent loci remained significant after multiple test correction (p < 0.001). Seven SNPs at five independent loci were associated with advanced prostate cancer defined as clinical stage ≥T3 or evidence of metastasis at diagnosis. Four independent SNPs were associated with advanced or aggressive cancer defined as stage ≥T3, metastasis, Gleason score ≥8, or World Health Organization grade 3 at diagnosis. Prostate cancer risk prediction with SNPs alone was less accurate than with PSA at baseline (area under the curve of 0.57 vs 0.79), with no benefit from combining SNPs with PSA. This study is limited by our reliance on clinical diagnosis of prostate cancer; there are likely undiagnosed cases among our control group.

Conclusions

Only a few previously reported SNPs were associated with prostate cancer risk in the large prospective Diet and Cancer cohort in Malmö, Sweden. SNPs were less useful in predicting prostate cancer risk than PSA at baseline.

Atopic diseases, such as asthma and allergic rhinitis, are common conditions that can influence sleep and subsequent daytime functioning. Children and patients with allergic conditions from ethnic minority groups might be particularly vulnerable to poor sleep and compromised daytime functioning because of the prevalence of these illnesses in these groups and the high level of morbidity. Research over the past 10 years has shed light on the pathophysiologic mechanisms (eg, inflammatory mediators) involved in many atopic diseases that can underlie sleep disruptions as a consequence of the presence of nocturnal symptoms. Associations between nocturnal symptoms and sleep and poorer quality of life as a result of missed sleep have been demonstrated across studies. Patients with severe illness and poor control appear to bear the most burden in terms of sleep impairment. Sleep-disordered breathing is also more common in patients with allergic diseases. Upper and lower airway resistance can increase the risk for sleep-disordered breathing events. In patients with allergic rhinitis, nasal congestion is a risk factor for apnea and snoring. Finally, consistent and appropriate use of medications can minimize nocturnal asthma or allergic symptoms that might disrupt sleep. Despite these advances, there is much room for improvement in this area. A summary of the sleep and allergic disease literature is reviewed, with methodological, conceptual, and clinical suggestions presented for future research.

Background

HIV infection has been associated with development of prediabetes and diabetes. Optimum screening practices for these disorders in HIV-infected populations remain unclear.

Methods

We screened 377 adults, with- or at-risk for HIV infection, for incident hyperglycaemia (prediabetes or diabetes) using two oral glucose tolerance tests (OGTTs) a median of 18.6 months apart. We determined proportion of incident cases detected by fasting and 120-min plasma glucose levels. Independent predictors of incident hyperglycaemia were identified using logistic regression.

Results

The baseline OGTT was consistent with diabetes in 7% of participants and with prediabetes in 31%. Among 352 normoglycaemic and prediabetic participants at baseline, 19 (5%) developed diabetes on follow-up. Among participants normoglycaemic at baseline, an additional 38 (16%) developed prediabetes. Overall 52% of incident hyperglycaemia cases were detected by fasting plasma glucose alone, 33% by a 120-min glucose level alone and 15% by both. Factors independently associated with incident hyperglycaemia included age ≥50 years and body mass index ≥30 kg/m2. Neither HIV infection nor highly active antiretroviral therapy (HAART) use were associated with increased risk of diabetes.

Conclusions

Incident hyperglycaemia is common among older adults with or at-risk for HIV infection. HIV-infected individuals with classic diabetes risk factors should be screened for hyperglycaemia regardless of HAART use. OGTTs may be the preferred screening strategy in HIV-infected individuals at high risk for developing hyperglycaemia.

The genetics of lymphoma susceptibility reflect the marked heterogeneity of diseases that comprise this broad phenotype. However, multiple subtypes of lymphoma are observed in some families, suggesting shared pathways of genetic predisposition to these pathologically distinct entities. Using a two-stage GWAS, we tested 530,583 SNPs in 944 cases of lymphoma, including 282 familial cases, and 4,044 public shared controls, followed by genotyping of 50 SNPs in 1,245 cases and 2,596 controls. A novel region on 11q12.1 showed association with combined lymphoma (LYM) subtypes. SNPs in this region included rs12289961 near LPXN, (PLYM = 3.89×10−8, OR = 1.29) and rs948562 (PLYM = 5.85×10−7, OR = 1.29). A SNP in a novel non-HLA region on 6p23 (rs707824, PNHL = 5.72×10−7) was suggestive of an association conferring susceptibility to lymphoma. Four SNPs, all in a previously reported HLA region, 6p21.32, showed genome-wide significant associations with follicular lymphoma. The most significant association with follicular lymphoma was for rs4530903 (PFL = 2.69×10−12, OR = 1.93). Three novel SNPs near the HLA locus, rs9268853, rs2647046, and rs2621416, demonstrated additional variation contributing toward genetic susceptibility to FL associated with this region. Genes implicated by GWAS were also found to be cis-eQTLs in lymphoblastoid cell lines; candidate genes in these regions have been implicated in hematopoiesis and immune function. These results, showing novel susceptibility regions and allelic heterogeneity, point to the existence of pathways of susceptibility to both shared as well as specific subtypes of lymphoid malignancy.

Author Summary

B-cell lymphomas comprise several diseases representing aberrant proliferations of immune cells at various stages of maturation. It might be expected that dissimilar subtypes of lymphoma will have different etiologic and pathogenic mechanisms, reflecting the distinct histologic and clinical characteristics of these diseases. This study aims to define both shared as well as specific genetic risk factors for lymphoma. Utilizing a genome-wide approach, we discovered novel locations in the genome associated with risk for lymphoid malignancies. Common variants in these regions, on chromosome 11q12.1 and 6p23, were each associated with a modest modification of risk for lymphoma. These regions harbor several genes of biological importance in lymphoid maturation and function. We also further characterized the HLA region at 6p21.32, previously associated with lymphoma risk and thought to be important in immune function. Some of the associated SNP markers were specific for one common subtype of lymphoma, e.g. follicular lymphoma. However, others were associated with combined subsets of disease, suggesting that there are both shared and subtype-specific associations between common genetic variants and human lymphoid cancer. Secondary analyses showed that the two novel regions harbor candidates that are biologically relevant and that regulate cell development and hematopoiesis.

The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.

A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals.

The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs.

Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements and potential direct medical cost savings achievable with the development and use of LFA medication delivery technologies.

Objective This article presents a summary of findings from asthma studies focusing on immigration and acculturation-related factors. A study examining associations between these processes, family cohesion and social support networks, and asthma morbidity in a sample of Dominican and Puerto Rican caregivers residing in the mainland U.S., is also described. Methods Latino children with asthma (n = 232), ages 7–16 (49% female) and their caregivers completed interview-based questionnaires on immigration and acculturation-related processes, family characteristics, and asthma morbidity. Results The frequency of ED use due to asthma may be higher for children of caregivers born in Puerto Rico. Acculturative stress levels were higher for Puerto Rican born caregivers residing in the mainland U.S. Conclusion Asthma-related educational and intervention programs for Latino children and families should be tailored to consider the effects that the immigration and acculturation experience can have on asthma management. Specific family-based supports focused on decreasing stress related to the acculturation process, and increasing social and family support around the asthma treatment process may help to reduce asthma morbidity in Latino children.

Background

This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and Glucocorticoid-induced osteoporosis (GIOP). The study’s objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts.

Methods

A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated.

For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of −3.0. The GIOP cohorts simulated had an initial BMD T-Score of −2.5.

Results

The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively.

Conclusions

The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold of €50,000.

While rhizome formation is intimately associated with perennialism and the derived benefit of sustainability, the introduction of this trait into temperate-zone adapted Sorghum cultivars requires precise knowledge of the genetics conditioning this trait in order to minimize the risk of weediness (e.g., Johnsongrass, S. halepense) while maximizing the productivity of perennial sorghum. As an incremental step towards dissecting the genetics of perennialism, a segregating F4 heterogeneous inbred family derived from a cross between S. bicolor and S. propinquum was phenotyped in both field and greenhouse environments for traits related to over-wintering and rhizome formation. An unseasonably cold winter in 2011 provided high selection pressure, and hence 74.8 % of the population did not survive. This severe selection pressure for cold tolerance allowed the resolution of two previously unidentified over-wintering quantitative trait locus (QTL) and more powerful correlation models than previously reported. Conflicting with previous reports, a maximum of 33 % of over-wintering variation could be explained by above-ground shoot formation from rhizomes; however, every over-wintering plant exhibited rhizome growth. Thus, while rhizome formation is required for over-wintering, other factors also determine survival in this interspecific population. The fine mapping of a previously reported rhizome QTL on sorghum chromosome SBI-01 was conducted by targeting this genomic region with additional simple sequence repeat markers. Fine mapping reduced the 2-LOD rhizome QTL interval from ~59 to ~14.5 Mb, which represents a 75 % reduction in physical distance and a 53 % reduction in the number of putative genes in the locus.

Electronic supplementary material

The online version of this article (doi:10.1007/s11032-012-9778-8) contains supplementary material, which is available to authorized users.

Though genome-wide association studies (GWAS) have identified numerous susceptibility loci for common diseases, their use is limited due to the expense of genotyping large cohorts of individuals. One potential solution is to use ‘additional controls’, or genotype data from control individuals deposited in public repositories. While this approach has been used by several groups, the genetically heterogeneous nature of the population of the United States makes this approach potentially problematic. We empirically investigated the utility of this approach in a US-based GWAS. In a small GWAS of pancreatic cancer in New York, we observed clear population structure differences relative to controls from the database of Genotypes and Phenotypes (dbGaP). When we conduct the GWAS using these additional controls, we find large inflation of the test statistic that is properly corrected by using eigenvectors from principal components analysis as covariates. To deal with errors introduced due to different sources, we propose simultaneously genotyping a small number of controls along with cases and then comparing this group to the additional controls. We show that removing SNPs that show differences between these control groups reduces false-positive findings. Thus, through an empirical approach, this report provides practical guidance for using additional controls from publicly available datasets.

Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity.

Background

The lifetime prevalence of self-reported asthma among Puerto Ricans is very high, with increased asthma hospitalizations, emergency department visits, and mortality rates. Differences in asthma severity between the mainland and island, however, remain largely unknown.

Objective

We sought to characterize differences in asthma severity and control among 4 groups: (1) Island Puerto Ricans, (2) Rhode Island (RI) Puerto Ricans, (3) RI Dominicans, and (4) RI whites.

Methods

Eight hundred five children aged 7 to 15 years completed a diagnostic clinic session, including a formal interview, physical examination, spirometry, and allergy testing. Using a visual grid adapted from the Global Initiative for Asthma, asthma specialists practicing in each site determined an asthma severity rating. A corresponding level of asthma control was determined by using a computer algorithm.

Results

Island Puerto Ricans had significantly milder asthma severity compared with RI Puerto Ricans, Dominicans, and whites (P < .001). Island Puerto Ricans were not significantly different from RI whites in asthma control. RI Puerto Ricans showed a trend toward less control compared with island Puerto Ricans (P = .061). RI Dominicans had the lowest rate of controlled asthma. Paradoxically, island Puerto Ricans had more emergency department visits in the past 12 months (P < .001) compared with the 3 RI groups.

Conclusions

Potential explanations for the paradoxic finding of milder asthma in island Puerto Ricans in the face of high health care use are discussed. Difficulties in determining guideline-based composite ratings for severity versus control are explored in the context of disparate groups.

Many studies have chronicled the “epidemiologic synergy” between human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). HIV adversely affects the natural history of HSV-2 and results in more frequent and severe HSV-2 reactivation. Few longitudinal studies, however, have examined whether HSV-2 is associated with increased HIV plasma viral loads or decreased CD4 counts. The authors estimated the effect of HSV-2 seropositivity on HIV RNA viral load and on CD4 count over time among 777 HIV-seropositive US women not receiving suppressive HSV-2 therapy in the HIV Epidemiology Research Study (1993–2000). Linear mixed models were used to assess the effect of HSV-2 on log HIV viral load and CD4 count/mm3 prior to widespread initiation of highly active antiretroviral therapy. Coinfection with HSV-2 was not associated with HIV RNA plasma viral loads during study follow-up. There was a statistically significant association between HSV-2 seropositivity and CD4 count over time, but this difference was small and counterintuitive at an increase of 8 cells/mm3 (95% confidence interval: 2, 14) per year among HSV-2-seropositive women compared with HSV-2-seronegative women. These data do not support a clinically meaningful effect of baseline HSV-2 seropositivity on the trajectories of HIV plasma viral loads or CD4 counts.

Predictors of liver fibrosis were evaluated in women using a noninvasive index (FIB-4). HIV RNA levels were associated with increased FIB-4 in the absence of viral hepatitis, alcohol use, or antiretroviral therapy. These data complement evidence suggesting a potential relationship between HIV infection and hepatic fibrosis.

Background. FIB-4 represents a noninvasive, composite index that is a validated measure of hepatic fibrosis, which is an important indicator of liver disease. To date, there are limited data regarding hepatic fibrosis in women.

Methods. FIB-4 was evaluated in a cohort of 1227 women, and associations were evaluated in univariate and multivariate regression models among 4 groups of subjects classified by their human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection status.

Results. The median FIB-4 scores were 0.60 in HIV-/HCV- women, 0.83 in HIV-/HCV+ women, 0.86 in HIV+/HCV- women, and 1.30 in HIV+/HCV+ women. In the HIV/HCV co-infected group, multivariate analysis showed that CD4+ cell count and albumin level were negatively associated with FIB-4 (P <.0001), whereas antiretroviral therapy (ART) was positively associated with FIB-4 score (P =.0008). For the HIV mono-infected group, multivariate analysis showed that CD4+ cell count (P <.0001) and albumin level (P =.0019) were negatively correlated with FIB-4 score, ART was positively associated with FIB-4 score (P =.0008), and plasma HIV RNA level was marginally associated with FIB-4 score (P =.080). In 72 HIV mono-infected women who were also hepatitis B surface antigen negative, ART naive, and reported no recent alcohol intake, plasma HIV RNA level was associated with increased FIB-4 score (P =.030).

Conclusions. HIV RNA level was associated with increased FIB-4 score in the absence of hepatitis B, hepatitis C, ART, or alcohol use, suggesting a potential relationship between HIV infection and hepatic fibrosis in vivo. A better understanding of the various demographic and virologic variables that contribute to hepatic fibrosis may lead to more effective treatment of HIV infection and its co-morbid conditions.

This study examined the relationship between obesity and asthma symptom perception in 200 youth with asthma. Repeated subjective and objective peak flow measurements were summarized using the Asthma Risk Grid (Klein et al., 2004), resulting in Accurate, Symptom Magnification and Danger Zone scores. Analyses were stratified by age and included ethnicity.

For younger children, obesity was not significantly related to perception scores. For older children, a significant obesity-by-ethnicity interaction for Accurate Symptom Perception scores indicated that obese white children had lower accuracy than white nonobese children, while there was no difference for obese versus nonobese minority children. Obesity was also related to higher Symptom Magnification scores regardless of ethnicity for older children.

These findings suggest that obesity may complicate asthma management by interfering with the ability to accurately perceive symptoms for some patients. More remains to be learned about the role of sociodemographic factors underlying this relationship.

Objective

To determine whether a multi-dimensional cumulative risk index (CRI) is a stronger predictor of asthma morbidity in urban, school-aged children with asthma, than poverty or severity alone.

Methods

A total of 163 children with asthma, ages 7–15 years (42% female; 69% ethnic minority) and their primary caregivers completed interview-based questionnaires, focusing on potential cultural, contextual, and asthma-specific risks that can impact asthma morbidity.

Results

Higher levels of cumulative risks were associated with more asthma morbidity, after controlling for poverty level or asthma severity. Analyses by ethnic group and subgroup also supported the relationship between the CRI and specific indices of asthma morbidity.

Conclusions

This study demonstrates the utility of multiple-dimensional risk models for predicting variations in asthma morbidity in urban children. Research efforts with urban families who have children with asthma need to consider the context of urban poverty as it relates to children’s cultural backgrounds and specific asthma outcomes.

The objective of this study was to examine associations between specific dimensions of the multidimensional cumulative risk index (CRI) and asthma morbidity in urban, school-aged children from African American, Latino and Non-Latino White backgrounds. An additional goal of the study was to identify the proportion of families that qualify for high-risk status on each dimension of the CRI by ethnic group. A total of 264 children with asthma, ages 7–15 (40% female; 76% ethnic minority) and their primary caregivers completed interview-based questionnaires assessing cultural, contextual, and asthma-specific risks that can impact asthma morbidity. Higher levels of asthma-related risks were associated with more functional morbidity for all groups of children, despite ethnic group background. Contextual and cultural risk dimensions contributed to more morbidity for African-American and Latino children. Analyses by Latino ethnic subgroup revealed that contextual and cultural risks are significantly related to more functional morbidity for Puerto Rican children compared to Dominican children. Findings suggest which type of risks may more meaningfully contribute to variations in asthma morbidity for children from specific ethnic groups. These results can inform culturally sensitive clinical interventions for urban children with asthma whose health outcomes lag far behind their non-Latino White counterparts.

This study determines asthma-related health care access and utilization patterns for Latino children of Puerto Rican and Dominican origin residing in Rhode Island (RI) and Latino children residing in Puerto Rico (Island). Data included 804 families of children with persistent asthma recruited from clinics. Island children were less likely to receive regular asthma care and care from a consistent provider and more likely to have been to the emergency department and hospitalized for asthma than RI children. Island children were 2.33 times more likely to have used the emergency department for asthma compared with RI non-Latino White (NLW) children. Latino children residing in both Island and RI were less likely to have used specialty care and more likely to have had a physician visit for asthma in the past year than RI NLW children. The differences might reflect the effects of the different delivery systems on pediatric health care utilization and asthma management.

Summary

Objective

Disparities in asthma outcomes exist between Latino and non-Latino white (NLW) children. We examined rates of medication use, medication beliefs, and perceived barriers to obtaining medication in US and island Puerto Rican parents of children with asthma

Hypotheses

Island PR parents would report the lowest rates of controller medication use, followed by RI Latino and RI NLW parents; Latino parents would report more medication concerns than NLW parents; and Island PR parents would report the most barriers to medication use.

Study Design

Five hundred thirty families of children with persistent asthma participated, including 231 Island PR, 111 RI NLW, and 188 RI Latino. Parents completed survey measures.

Results

Group differences were found on reported use of ICS (X2 = 50.96, P <0.001), any controller medication (X2 = 56.49, P <0.001), and oral steroids (X2 = 10.87, P <0.01). Island PR parents reported a greater frequency of barriers to medication use than the other two groups (X2 = 61.13, P <0.001). Latino parents in both sites expressed more medication concerns than NLW parents (F = 20.18, P <0.001). Medication necessity was associated with ICS use in all three groups (all P’s <0.01). Medication concerns were positively associated with ICS use in PR only (OR = 1.64, P <0.05).

Conclusions

Differences in medication beliefs and the ability to obtain medications may explain the reported disparity in controller medication use. Further studies are needed to evaluate these obstacles to medication use.

Summary

Background

Epidemiologic studies have documented higher rates of asthma prevalence and morbidity in minority children compared to non-Latino white (NLW) children. Few studies focus on the mechanisms involved in explaining this disparity, and fewer still on the methodological challenges involved in rigorous disparities research.

Objectives and Methods

This article provides an overview of challenges and potential solutions to research design for studies of health disparities. The methodological issues described in this article were framed on an empirical model of asthma health disparities that views disparities as resulting from several factors related to the healthcare system and the individual/community system. The methods used in the Rhode Island–Puerto Rico Asthma Center are provided as examples, illustrating the challenges in executing disparities research.

Results

Several methods are described: distinguishing ethnic/racial differences from methodological artifacts, identifying and adapting culturally sensitive measures to explain disparities, and addressing the challenges involved in determining asthma and its severity in Latino and other minority children. The measures employed are framed within each of the components of the conceptual model presented.

Conclusions

Understanding ethnic and/or cultural disparities in asthma morbidity is a complicated process. Methodologic approaches to studying the problem must reflect this complexity, allowing us to move from documenting disparities to understanding them, and ultimately to reducing them.

Objective. To identify correlates of incident bacterial vaginosis (BV) diagnosed with Nugent scoring among high-risk women. Study Design. We conducted both cohort and case-crossover analyses, stratified by HIV infection status, based on 871 HIV-infected and 439 HIV-uninfected participants in the HIV Epidemiology Research Study, conducted in 4 US sites in 1993–2000. Results. BV incidence was 21% and 19% among HIV-infected and -uninfected women, respectively. Fewer correlates of BV were found with case-crossover than with cohort design. Reporting frequent coitus (regardless of consistency of condom use) was correlated with BV in cohort analyses but not in case-crossover analyses. The sole correlate of BV in both types of analyses was the detection of spermatozoa on Gram stain, which is a marker of semen exposure. Conclusion. The inconsistent association between condom use and BV in prior studies could be from reporting bias. We found evidence of a relationship between semen exposure and incident BV.

Background

Higher plants exhibit remarkable phenotypic plasticity allowing them to adapt to an extensive range of environmental conditions. Sorghum is a cereal crop that exhibits exceptional tolerance to adverse conditions, in particular, water-limiting environments. This study utilized next generation sequencing (NGS) technology to examine the transcriptome of sorghum plants challenged with osmotic stress and exogenous abscisic acid (ABA) in order to elucidate genes and gene networks that contribute to sorghum's tolerance to water-limiting environments with a long-term aim of developing strategies to improve plant productivity under drought.

Results

RNA-Seq results revealed transcriptional activity of 28,335 unique genes from sorghum root and shoot tissues subjected to polyethylene glycol (PEG)-induced osmotic stress or exogenous ABA. Differential gene expression analyses in response to osmotic stress and ABA revealed a strong interplay among various metabolic pathways including abscisic acid and 13-lipoxygenase, salicylic acid, jasmonic acid, and plant defense pathways. Transcription factor analysis indicated that groups of genes may be co-regulated by similar regulatory sequences to which the expressed transcription factors bind. We successfully exploited the data presented here in conjunction with published transcriptome analyses for rice, maize, and Arabidopsis to discover more than 50 differentially expressed, drought-responsive gene orthologs for which no function had been previously ascribed.

Conclusions

The present study provides an initial assemblage of sorghum genes and gene networks regulated by osmotic stress and hormonal treatment. We are providing an RNA-Seq data set and an initial collection of transcription factors, which offer a preliminary look into the cascade of global gene expression patterns that arise in a drought tolerant crop subjected to abiotic stress. These resources will allow scientists to query gene expression and functional annotation in response to drought.

Background

Beta-microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate, and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5’ region of the gene which encodes MSP (MSMB), has recently been identified as a risk factor for prostate cancer.

Methods

We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels.

Results

We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P<10−8) with carriers of the C allele having lower geometric mean MSP levels (ng/mL) (CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans 25.8/16.4/6.7). We estimated the variant accounts for 30–50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P=3.5×10−6), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans.

Conclusions

Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations.

Impact

This supports the hypothesis that rs10993994 may be the biologically functional allele.

Objective

To investigate rates and predictors of change in bone mineral density (BMD) in a cohort of aging men with or at risk for HIV infection.

Design

Prospective cohort study among 230 HIV-infected and 159 HIV-uninfected men aged ≥49 years.

Methods

Longitudinal analyses of annual change in BMD at the femoral neck, total hip and lumbar spine.

Results

At baseline 46% of men had normal BMD, 42% had osteopenia, and 12% had osteoporosis. Of those men with normal BMD, 14% progressed to osteopenia and 86% continued to have normal BMD. Of the men initially with osteopenia, 12% progressed to osteoporosis, and 83% continued to have osteopenia. Osteopenia incidence per 100 person-years at risk (PYAR) was 2.6 for HIV-uninfected men and 7.2 for HIV-infected men; osteoporosis incidence was 2.2/100 PYAR among men with osteopenia, regardless of HIV status. In multivariable analysis of annual change in BMD at the femoral neck, we found a significant interaction between heroin use and AIDS diagnosis, such that the greatest bone loss occurred with both AIDS and heroin use (adjusted predicted mean annual bone loss 0.0196 gm/cm2). Hepatitis C virus seropositivity was also associated with femoral neck bone loss (p=.04). The interaction between AIDS and heroin use also was associated with bone loss at the total hip, as was current methadone use (p<.01).

Conclusions

We found an association of heroin use and AIDS with BMD change, suggesting that heroin users with AIDS may be at particular risk for bone loss.

Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited.

Objective. To evaluate associations between common vaginal infections and human papillomavirus (HPV). Study Design. Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. Results. Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. Conclusion. These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.