Evolution of illicit opioid use among people with HIV infection in St Petersburg, Russia, in the period 2004-2015.

OBJECTIVES: In the late 1990s, when the current Russian opioid epidemic began, illicit opioids used in Russia consisted almost exclusively of heroin. The type of opioids used has evolved in the early 21st Century. The objective of this study was to describe the evolution of illicit opioid use among people living with HIV (PLWH) reporting recent opioid use in St Petersburg, Russia. METHODS: We examined baseline data from four research studies conducted in the period 2004-2015 that included PLWH who used opioids [Partnership to Reduce the Epidemic Via Engagement in Narcology Treatment (PREVENT; 2004-2005; n = 17), HIV Evolution in Russia-Mitigating Infection Transmission and Alcoholism in a Growing Epidemic (HERMITAGE; 2007-2010; n = 281), Linking Infectious and Narcology Care (LINC; 2013-2014; n = 119) and Russia Alcohol Research Collaboration on HIV/AIDS (Russia ARCH; 2012-2015; n = 121)] and reported recent use of heroin and other opioids. RESULTS: Although these studies spanned more than a decade, the participants represented similar birth cohorts; the mean age was 24.5 years in 2004 and 33.3 years in 2014. The use of opioid types, however, evolved across cohorts, with the use of any illicit drug other than heroin increasing from 6% [95% confidence interval (CI) 000.2, 29%] in PREVENT (2004-2005) to 30% (95% CI 25, 36%) in HERMITAGE (2007-2010) to 70% (95% CI 61, 78%) in LINC (2013-2014) to 77% (95% CI 68, 84%) in ARCH (2012-2015). Any heroin use consistently decreased over the 10-year period in the cohorts, from 100% (95% CI 80, 100%) in 2004-2005 to 54% (95% CI 44, 63%) in 2012-2015. CONCLUSIONS: Among PLWH who use opioids in St Petersburg, Russia, illicit use of opioids other than heroin appears to be more common than heroin use.

Fumigant Toxicity and Repellence Activity of Camphor Essential Oil from Cinnamonum camphora Siebold Against Solenopsis invicta Workers (Hymenoptera:Formicidae).

The red imported fire ant (RIFA) Solenopsis invicta Buren causes severe damage to humans and animals as well as the environment. Chemical treatment is the main strategy of RIFA management, which also is potentially toxic to the environment. Plant essential oils (EOs) are considered as potential substance that can be used to control insects. This study aimed to identify the chemical composition of camphor EO and investigate the insecticidal activity on RIFAs. The chemical composition of the EO was analyzed by gas chromatography/mass spectrometry and gas chromatography with flame ionization detection. Results revealed that 36.61% camphor and 30.05% cineole were the major components. The insecticidal activity of camphor EO was assessed against RIFA workers by conducting two different bioassays: fumigant toxicity and repellence. Fumigant toxicity assay results showed that the lethal dose (LC50) of the EO at 24 h was 1.67 and 4.28 µg/ml for minor and major workers, respectively; knockdown time (KT50) was 10.82 and 14.73 h. At 2.55 µg/ml, the highest average mortality of the ants was 84.89% after 72 h. Camphor EO exhibited fumigant toxicity against minor and major workers as indicated by the effects on attacking, feeding, and climbing behaviors. This EO was also strongly repellent to the two size workers of the colony as observed in their behavior against Tenebrio molitor treated with 5 µl EO. The fumigant toxicity and repellence of camphor EO against RIFA indicated that this substance could be a potential alternative for the development of eco-friendly products used to control pests.

Compounds leached from quinoa seeds inhibit matrix metalloproteinase activity and intracellular reactive oxygen species.

OBJECTIVE: Quinoa (Chenopodium quinoa Willd.) is a seed crop rich in bioactive compounds including phytoecdysones (especially 20-hydroxyecdysone, 20HE), polyphenols, proteins and essential fatty acids. We previously reported a method to leach and concentrate quinoa bioactives into a complex phytochemical mixture termed quinoa leachate (QL). Here, we aimed to determine the effect of QL and its chemically distinct fractions on five biochemical endpoints relevant to skin care applications: (i) cell viability, (ii) matrix metalloproteinase (MMP) mRNA expression, (iii) MMP enzymatic activity, (iv) tyrosinase enzymatic activity and (v) intracellular reactive oxygen species (ROS) production. METHODS: Quinoa leachate was fractionated and chemically characterized using column chromatography and liquid chromatography-mass spectrometry (LC-MS). Cell viability was determined using a MTT assay in four mammalian cell lines. MMP-1 mRNA expression was assessed in human dermal fibroblasts (HDF) via qRT-PCR. The enzymatic activity of MMP-9 and tyrosinase was measured using fluorometric and colorimetric in vitro assays, respectively. Lipopolysaccharide (LPS)-induced ROS production was determined in human dermal fibroblasts by fluorescence intensity of an oxidant-sensitive probe. RESULTS: Quinoa leachate was separated into three fractions: (i) carbohydrate-rich fraction (QL-C; 71.3% w/w of QL); (ii) phytoecdysone, polyphenol and protein-rich fraction (QL-P, 13.3% w/w of QL); (iii) oil-rich fraction (QL-O, 10.8% w/w of QL). QL did not reduce cell viability in any of the four cell lines tested. QL, QL-P and QL-O each significantly inhibited MMP-1 mRNA expression in HDF at a concentration of 5 µg mL(-1) . QL and QL-P also significantly inhibited MMP-9 enzymatic activity, whereas QL-P demonstrated significant tyrosinase enzymatic inhibition. Furthermore, QL, QL-P, QL-O and 20HE significantly inhibited intracellular ROS production. CONCLUSION: This study is the first to demonstrate the MMP, tyrosinase and ROS inhibiting properties of multiple different phytochemical components derived from quinoa seeds. Our work indicates that quinoa phytochemicals may play a role in the treatment and prevention of skin ageing through a multiplicity of effects.

Factors associated with study attrition among HIV-infected risky drinkers in St. Petersburg, Russia.

BACKGROUND: Participant attrition in HIV longitudinal studies may introduce bias and diminish research quality. The identification of participant characteristics that are predictive of attrition might inform retention strategies. OBJECTIVE: The study aimed to identify factors associated with attrition among HIV-infected Russian risky drinkers from the secondary HIV prevention HERMITAGE trial. We examined whether current injection drug use (IDU), binge drinking, depressive symptoms, HIV status nondisclosure, stigma, and lifetime history of incarceration were predictors of study attrition. We also explored effect modification due to gender. METHODS: Complete loss to follow-up (LTFU), defined as no follow-up visits after baseline, was the primary outcome, and time to first missed visit was the secondary outcome. We used multiple logistic regression models for the primary analysis, and Cox proportional hazards models for the secondary analysis. RESULTS: Of 660 participants, 101 (15.3%) did not return after baseline. No significant associations between independent variables and complete LTFU were observed. Current IDU and HIV status nondisclosure were significantly associated with time to first missed visit (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.03-1.87; AHR, 1.38; 95% CI, 1.03-1.86, respectively). Gender stratified analyses suggested a larger impact of binge drinking among men and history of incarceration among women with time to first missed visit. CONCLUSIONS: Although no factors were significantly associated with complete LTFU, current IDU and HIV status nondisclosure were significantly associated with time to first missed visit in HIV-infected Russian risky drinkers. An understanding of these predictors may inform retention efforts in longitudinal studies.

The influence of depressive symptoms on alcohol use among HIV-infected Russian drinkers.

BACKGROUND: Depressive symptoms have been linked to HIV progression through a number of biobehavioral mechanisms including increased alcohol use. Although research supports an association between alcohol use and depressive symptoms among HIV patients, there have been few studies that have examined whether depressive symptoms predict subsequent drinking, especially among heavy drinking HIV-infected patients. METHOD: Heavy drinking Russian HIV-infected patients (n=700) were recruited from addiction and HIV care settings for a randomized controlled trial of a risk reduction intervention [HERMITAGE]. GEE overdispersed Poisson regression analyses were conducted to assess the association between depressive symptoms and alcohol consumption 6-months later. RESULTS: In adjusted analyses, depressive symptom severity was significantly associated with drinks per day (global p=.02). Compared to the non-depressed category, mild depressive symptoms were significantly associated with more drinks per day [IRR=1.55, (95% CI: 1.14, 2.09)], while moderate [IRR=1.14, (95% CI: 0.83, 1.56)] and severe [IRR=1.48, (95% CI: 0.93, 2.34)] depressive symptoms were not. Associations between depressive symptom severity and heavy drinking days were not statistically significant (global p=.19). Secondary analyses using the BDI-II screening threshold (BDI-II>14) and the BDI-II cognitive subscale suggested an association between depressive symptoms and drinks per day over time but not heavy episodic drinking. CONCLUSIONS: Among heavy drinking HIV-infected patients, elevated depressive symptoms were associated with greater subsequent alcohol use. These findings suggest that depressive symptoms may be important to address in efforts to reduce alcohol-related risks among HIV-infected populations.

History of intimate partner violence is associated with sex work but not sexually transmitted infection among HIV-positive female drinkers in Russia.

This paper assesses the associations between intimate partner violence (IPV) and sexually transmitted infections (STIs) and sexual risks among HIV-positive female drinkers in St Petersburg, Russia. Survey and STI data were analysed from 285 women in HERMITAGE, a secondary prevention study of HIV-positive heavy drinkers. Logistic and Poisson regression analyses assessed associations of IPV with STI and risky sex. Most women (78%) experienced IPV and 19% were STI positive; 15% sold sex. IPV was not significantly associated with STI, but was with selling sex (adjusted odds ratio = 3.56, 95% confidence interval = 1.02-12.43). In conclusion, IPV is common and associated with sex trade involvement among Russian HIV-positive female drinkers.

Homocysteine levels and cognitive function scores measured with MMSE and BCAT of middle-aged and elderly subjects in Tianjin City.

OBJECTIVE: China is proceeding into the aging society. There are near 6 million elderly suffering senile dementia,while cognitive impairment is an important clinical feature in dementia. The factors involved in cognitive dysfunction in the middle-aged and the elderly persons were investigated. DESIGN: Cross-sectional study. SETTING: Community dwellers and nursing home residents in Tianjin, China. SUBJECTS: Total of 662 subjects(284 men and 378 women) aged 55-93. METHODS: A designed questionnaire was used to collect their demographic data, information of disease and medication, and life style. Mini-mental state examination (MMSE) and Basic Cognitive Aptitude Tests (BCAT) software were applied to evaluate their cognitive function. Serum total homocysteine (tHcy) level was quantified by enzyme conversion method. A multiple linear stepwise regression analysis was applied to find the influencing factors of cognitive function. RESULTS: The average serum tHcy concentrations was 15.95±7.29 µmol/L, while the prevalence of hyperhomocysteinemia (HHE) was 45.4%. The average serum tHcy level and prevalence of HHE were higher in men than those in women after ruling out the age differences. The mean MMSE and BCAT scores were 26.74±2.71 and 50.26±18.84 respectively. The BCAT score was negatively correlated with age and positively correlated with education. Multiple linear stepwise regression equations showed that the P value was less than 0.001, the BCAT regression equation showed that the R2=0.453. Serum tHcy concentration was negatively correlated with total scores of BCAT, digit copy, Chinese character comparison, mental arithmetic, Chinese character rotation and recall answer of mental arithmetic test. Total scores of BCAT were negatively correlated with education, inhabitancy, serum tHcy concentration and age. In addition, Chinese character rotation was correlated with tea consumption. Remembrance and recognition of dual words and nonsense figures was correlated with income level. CONCLUSIONS: Hyperhomocysteinemia is associated with cognitive impairment in the middle-aged and the elderly persons in Tianjin. The BCAT scores could well represent the detailed cognitive function in elderly and negatively correlate with age, but positively correlated with education level. Serum tHcy concentration was negatively correlated with total BCAT scores.

Sexually transmitted infections among HIV-infected heavy drinkers in St Petersburg, Russia.

The objective of this study was to estimate the prevalence and identify correlates of four sexually transmitted infections (STIs) among HIV-infected Russians reporting heavy alcohol use and recent unprotected sex, we conducted a cross-sectional analysis of baseline data from the HERMITAGE study. The primary outcome was any current STI, based on urine tests for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis and serological testing for infection with Treponema pallidum. Data on potential demographic and behavioural predictors of STI were obtained from surveys administered at study entry. Of 682 participants, 12.8% (95% confidence interval [CI] 10.3, 15.3) tested positive for at least one STI. In a multivariable model adjusted for gender, age and marital status, only sex trade involvement over the last three months was significantly associated with an increased odds of STI (adjusted odds ratio [AOR] 2.00, 95% CI 1.13, 3.55). Given that STIs were common in this HIV-infected cohort, and that few patient characteristics predicted STI, the current practice of screening HIV-infected Russians for syphilis alone merits re-evaluation.

Co-culture of mechanically injured cartilage with joint capsule tissue alters chondrocyte expression patterns and increases ADAMTS5 production.

We studied changes in chondrocyte gene expression, aggrecan degradation, and aggrecanase production and activity in normal and mechanically injured cartilage co-cultured with joint capsule tissue. Chondrocyte expression of 21 genes was measured at 1, 2, 4, 6, 12, and 24h after treatment; clustering analysis enabled identification of co-expression profiles. Aggrecan fragments retained in cartilage and released to medium and loss of cartilage sGAG were quantified. Increased expression of MMP-13 and ADAMTS4 clustered with effects of co-culture, while increased expression of ADAMTS5, MMP-3, TGF-beta, c-fos, c-jun clustered with cartilage injury. ADAMTS5 protein within cartilage (immunohistochemistry) increased following injury and with co-culture. Cartilage sGAG decreased over 16-days, most severely following injury plus co-culture. Cartilage aggrecan was cleaved at aggrecanase sites in the interglobular and C-terminal domains, resulting in loss of the G3 domain, especially after injury plus co-culture. Together, these results support the hypothesis that interactions between injured cartilage and other joint tissues are important in matrix catabolism after joint injury.

Binge drinking and unsafe sex: a study of narcology hospital patients from St. Petersburg, Russia.

The purpose of this study was to assess the association between binge alcohol use and unprotected sex in Russian substance users. Participants (N = 181) were narcology hospital patients assessed on demographics, alcohol use, risky sex, and sexually transmitted disease/human immunodeficiency virus (STD/HIV) diagnoses. Adjusted generalized estimating equations (GEEs) logistic regression analysis examined the association between binge drinking and same-day unprotected sex across each of the past 30 days, per participant (N = 5430 observations). Participants were age 18 to 55 years, 75% male, and 64% binge drinking. Sex trade was reported by 27%; history of STDs by 43%; and HIV by 15%. One fourth of daily observations included sex; 88% of these involved unprotected sex. Binge drinking was not associated with same-day unprotected sex (adjusted odds ratio [OR(adj)] = 1.0, 95% confidence interval [CI] = 0.7-1.4, chi(2)(1, N = 5219) = 0.01, ns). Findings document substantial HIV/STD risk and prevalence among Russian narcology patients, but no link between binge drinking and unprotected sex in this population, possibly due to very low rates of condom use generally.

Impact of parental home smoking policies on policy choices of independently living young adults.

OBJECTIVE: To determine whether adolescents living in parental homes where smoking is banned are more likely to move into smoke-free living quarters when they leave home. METHODS: We analysed data on 693 youths from a 4-year, three-wave prospective study of a representative sample of Massachusetts adolescents (aged 12-17). All youths resided in independent living quarters at follow-up. The primary outcome was presence of a smoking ban in the living quarters at follow-up. The primary predictor was presence of a household smoking ban in the parental home, assessed 2 years before the outcome. Generalised linear mixed effects models examined the effect of a parental household smoking ban on the odds of moving into smoke-free living quarters at follow-up overall and stratified by smoking status at follow-up. RESULTS: Youths leaving home had much higher odds of moving to smoke-free living quarters if their parental household had had a smoking ban (odds ratio (OR) = 12.70, 95% CI, 6.19 to 26.04). Other independent predictors included moving into a school or college residence (OR = 3.88, 95% CI 1.87 to 8.05), and not living with smokers at follow-up (OR = 3.91, 95% CI 1.93 to 7.92). CONCLUSIONS: A household smoking ban in the parental home appears to lead youths to prefer smoke-free living quarters once they leave home.

Correlates of any condom use among Russian narcology patients reporting recent unprotected sex.

The purpose of this study was to assess whether HIV/sexually transmitted infection (STI) risk factors: risky sex (multiple sex partners and sex trade involvement), past HIV or STI diagnosis and substance use (at risk drinking and injection drug use) are associated with the outcome any condom use in the past 6 months among Russian narcology hospital patients. Participants (N = 178) included only those who reported unprotected sex in the past 6 months and were aged 18-55 years and 76% male. Any condom use in the past 6 months was reported by 55% of the sample. History of STIs was reported by 43% of participants; 15% were HIV-infected. Regression analyses adjusted for demographics demonstrated that those reporting multiple sex partners (OR(adj) = 4.2, 95% CI = 2.0-8.7) and sex trade involvement (OR(adj) = 2.4, 95% CI = 1.1-5.1) in the past 6 months had significantly higher odds of reporting any condom use in this same timeframe. HIV/STI and substance use were not associated with increased odds of condom use.

Factors associated with discontinuation of antiretroviral therapy in HIV-infected patients with alcohol problems.

Although mortality rates among HIV-infected populations have declined with the advent of combination antiretroviral therapy (ART), patients with substance use disorders have benefited less from these therapies. While adherence to ART has been well studied, less is known about factors associated with discontinuation of ART. The aim of this study is to investigate predictors of discontinuation of ART in HIV-infected patients with alcohol problems, focusing on their substance use and depressive symptoms. The study cohort (n=266) was prospectively assessed with biannual standardised interviews between 2001 and 2005. Four predictor variables (cocaine, heroin, heavy alcohol use and substantial depressive symptoms) were assessed six months prior to the outcome (ART discontinuation). Longitudinal logistic regression models examined the association between predictor variables and ART discontinuation adjusting for age, gender, race/ethnicity, homelessness, CD4, HIV RNA and HIV Symptom Index. Subjects were 77% male; 43% black; 22% homeless; 45% used cocaine; 20% used heroin; 29% had heavy alcohol use; and 40% had substantial depressive symptoms. Discontinuation occurred in 135 (17%) of the observations (n=743). In bivariate analyses, cocaine use, heroin use and depressive symptoms were significantly associated with ART discontinuation but heavy alcohol use was not. In the multivariable model, substantial depressive symptoms (adjusted odds ratio (AOR)=1.66; 95% confidence interval (CI): 1.04, 2.65) but not cocaine (AOR=1.28; 95%CI: 0.76, 2.16) or heroin use (AOR=1.27 95%CI: 0.66, 2.44), remained significantly associated with ART discontinuation. Among HIV-infected adults with alcohol problems, depressive symptoms, but not substance use, predicted subsequent ART discontinuation. Recognition and treatment of depressive symptoms in this population may result in better maintenance of ART and its associated clinical benefits.

Effect of local restaurant smoking regulations on progression to established smoking among youths.

BACKGROUND: While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis. OBJECTIVE: To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents. DESIGN, SETTING, AND SUBJECTS: A cohort of 2623 Massachusetts youths, ages 12-17 years at baseline, was interviewed via random digit dial telephone survey in 2001-2002 and followed up two years later. A generalised estimating equations (GEE) logistic regression analysis was used and controlled for potential individual, household, and town level confounding factors. MAIN OUTCOME MEASURE: Progression to established smoking during the two year follow up period (defined as having smoked 100 or more cigarettes in one's life). RESULTS: Compared to youths living in towns with weak regulations, those living in towns with strong regulations (complete restaurant smoking bans) had less than half the odds of progression to established smoking (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.24 to 0.66). The association was stronger for youths in towns with strong regulations in effect for two or more years (OR 0.11, 95% CI 0.03 to 0.37), although it was still present for those in towns with strong regulations in effect for less than two years (OR 0.55, 95% CI 0.33 to 0.90). No relationship was found between living in a town with a medium restaurant smoking regulation (restriction of smoking to enclosed, separately ventilated areas) and rates of progression to established smoking. CONCLUSIONS: Local restaurant smoking bans may be an effective intervention to prevent youth smoking.

Relation between local restaurant smoking regulations and attitudes towards the prevalence and social acceptability of smoking: a study of youths and adults who eat out predominantly at restaurants in their town.

OBJECTIVE: To examine the relation between strength of local restaurant smoking regulations and smoking related social norms among youths and adults. DESIGN: We used generalised estimating equations logistic regression analysis to examine the relation between regulation strength and youths' and adults' perceptions of adult smoking prevalence and the social acceptability of smoking in their town, while controlling for baseline anti-smoking sentiment in the town. SETTING: Each of the 351 Massachusetts towns were classified as having strong (complete smoking ban), medium (restriction of smoking to enclosed, separately ventilated areas), or weak (all others) restaurant smoking regulations. SUBJECTS: 1147 Massachusetts youths ages 12-17 years and 2116 adults who reported that they often or always eat out in their own town, drawn from a random digit dial survey. MAIN OUTCOME MEASURES: Perceived adult smoking prevalence and perceived social acceptability of smoking in restaurants, in bars, or in general. RESULTS: Compared to youths from towns with weak regulations, youths from towns with strong regulations were more likely to perceive lower adult smoking prevalence (odds ratio (OR) 1.71; 95% confidence interval (CI) 1.02 to 2.84) and social unacceptability of adult smoking (OR 2.00, 95% CI 1.29 to 3.08) in their town. Adults from towns with strong regulations were not more likely to perceive lower adult smoking prevalence, but had more than twice the odds of perceiving that smoking was unacceptable in restaurants (OR 2.19, 95% CI 1.58 to 3.02) or bars (OR 2.51, 95% CI 1.90 to 3.31). CONCLUSIONS: Strong local restaurant smoking regulations are associated with favourable smoking related social norms among youths and adults.

Effect of highly active antiretroviral therapy on survival in patients with AIDS-associated pulmonary Kaposi's sarcoma treated with chemotherapy.

PURPOSE: Kaposi's sarcoma (KS) is the most common AIDS-related malignancy. Pulmonary involvement by KS (PKS) has carried a poor prognosis with median reported survival ranging from 3 to 10 months. We studied whether the introduction of highly active antiretroviral therapy (HAART; triple antiretroviral therapy including a protease inhibitor and two reverse transcriptase inhibitors) has been associated with improved survival for AIDS patients with PKS. PATIENTS AND METHODS: A retrospective study was performed of 37 consecutive patients with PKS and human immunodeficiency virus infection in the tumor registry at a large municipal hospital in New York City between 1994 to 1997. There were 16 patients from 1994 to 1995 (pre-HAART period) and 21 patients from 1996 to 1997 (post-HAART period). The primary end point was survival, which was defined as time from start of chemotherapy until death from any cause. RESULTS: Patients were analyzed by the date of diagnosis (pre- v post-HAART period) and whether or not they received HAART. Kaplan-Meier analysis showed significantly better survival in patients diagnosed in the post-HAART period (P =.0025). Additional Kaplan-Meier analysis indicated that patients on HAART had substantially better survival (P <.0001). Cox multivariate analyses showed that HAART therapy was associated with a reduced risk of death (hazard ratio = 0.09; 95% confidence interval, 0.03 to 0.69). CONCLUSION: In patients with AIDS-associated PKS and undergoing chemotherapy, administration of HAART was associated with increased survival.

Biosynthetic response and mechanical properties of articular cartilage after injurious compression.

Traumatic joint injury is known to produce osteoarthritic degeneration of articular cartilage. To study the effects of injurious compression on the degradation and repair of cartilage in vitro, we developed a model that allows strain and strain rate-controlled loading of cartilage explants. The influence of strain rate on both cartilage matrix biosynthesis and mechanical properties was assessed after single injurious compressions. Loading with a strain rate of 0.01 s(-1) to a final strain of 50% resulted in no measured effect on the cells or on the extracellular matrix, although peak stresses reached levels of about 12 MPa. However, compression with strain rates of 0.1 and 1 s(-1) caused peak stresses of approximately 18 and 24 MPa, respectively, and resulted in significant decreases in both proteoglycan and total protein biosynthesis. The mechanical properties of the explants (compressive and shear stiffness) were also reduced with increasing strain rate. Additionally, cell viability decreased with increasing strain rate, and the remaining viable cells lost their ability to exhibit an increase in biosynthesis in response to low-amplitude dynamic mechanical stimulation. This latter decrease in reparative response was most dramatic in the tissue compressed at the highest strain rates. We conclude that strain rate (like peak stress or strain) is an important parameter in defining mechanical injury, and that cartilage injuriously compressed at high strain rates can lose its characteristic anabolic response to low-amplitude cyclic mechanical loading.

MEIS1 and HOXA7 genes in human acute myeloid leukemia.

Co-activation of Meisl with Hoxa7 or Hoxa9 homeobox genes by retroviral gene insertion has recently been reported to be leukemogenic in murine myeloid leukemia. In this study we determined their expression in human leukemia. Most human myeloid leukemia cell lines co-expressed MEIS1 with HOXA7 and HOXA9. Among patients with acute leukemia, 50% of AML patients expressed MEIS1, while the majority of ALL patients were negative. A total of 89.5% of patients expressing MEIS1 co-expressed HOXA7. In unadjusted models, poorer response to chemotherapy was associated with expression of HOXA7 regardless of MEIS1 status and older patients were more likely to express either gene.

The one-sample problem from eradication studies of chronic viral infections.

In studies of chronic viral infections, the objective is to estimate probabilities of developing viral eradication and resistance. Complications arise as the laboratory methods used to assess eradication status result in unusual types of censored observations. This paper proposes nonparametric methods for the one-sample analysis of viral eradication/resistance data. We show that the unconstrained nonparametric maximum likelihood estimator of the subdistributions of eradication and resistance are obtainable in closed form. In small samples, these estimators may be inadmissible; thus, we also present an algorithm for obtaining the constrained MLEs based on an isotonic regression of the unconstrained MLEs. Estimators of several functionals of the eradication and resistance subdistributions are also developed and discussed. The methods are illustrated with results from recent hepatitis C clinical trials.

Covariate analysis of viral eradication studies.

An important issue arising in therapeutic studies of hepatitis C and HIV is the identification of and adjustment for covariates associated with viral eradication and resistance. Analyses of such data are complicated by the fact that eradication is an occult event that is not directly observable, resulting in unique types of censored observations that do not arise in other competing risks settings. This paper proposes a semiparametric regression model to assess the association between multiple covariates and the eradication/resistance processes. The proposed methods are based on a piecewise proportional hazards model that allows parameters to vary between observation times. We illustrate the methods with data from recent hepatitis C clinical trials.