A marginal structural model for multiple‐outcome survival data:assessing the impact of injection drug use on several causes of death in the Canadian Co‐infection Cohort

It is often the case that interest lies in the effect of an exposure on each of several distinct event types. For example, we are motivated to investigate in the impact of recent injection drug use on deaths due to each of cancer, end‐stage liver disease, and overdose in the Canadian Co‐infection Cohort (CCC). We develop a marginal structural model that permits estimation of cause‐specific hazards in situations where more than one cause of death is of interest. Marginal structural models allow for the causal effect of treatment on outcome to be estimated using inverse‐probability weighting under the assumption of no unmeasured confounding; these models are particularly useful in the presence of time‐varying confounding variables, which may also mediate the effect of exposures. An asymptotic variance estimator is derived, and a cumulative incidence function estimator is given. We compare the performance of the proposed marginal structural model for multiple‐outcome data to that of conventional competing risks models in simulated data and demonstrate the use of the proposed approach in the CCC. Copyright © 2013 John Wiley & Sons, Ltd.     

Alcohol Consumption and Risky Sexual Behavior Among Persons Attending Alcohol Consumption Venues in Gaborone,Botswana

Alcohol use is a known key risk factor associated with risky sexual behavior that contributes to HIV transmission. This cross-sectional study used time location sampling to investigate alcohol use and risky sexual behaviors that occurred after ingesting alcohol among 609 patrons of alcohol venues in Gaborone, Botswana. Alcohol Use Disorders Identification Test (AUDIT) scores were categorized as low (1–7), medium (8–15), and high (16+) for analysis. Logistic regression models stratified by gender assessed the association between alcohol use and condom use at last sex after drinking alcohol. Among females, the odds of condom use during last sex after drinking alcohol were significantly lower for high compared to low AUDIT scores (AOR?=?0.17, 95 % CI 0.06–0.54). Among males, factors significantly associated with condom use at last sex after alcohol use were low levels of education (primary level compared to university and above AOR?=?0.13; 95 % CI 0.03–0.55) and beliefs that alcohol use did not increase risky sexual behaviors (AOR?=?0.26; 95 % CI 0.11–0.62). HIV prevention interventions should target females and emphasize sexual risks associated with alcohol use.     

Juçara (Euterpe edulis Mart.) Supplementation Reduces Aberrant Crypt Foci and Increases SOD1 Expression in the Colorectal Mucosa of Carcinogenesis-Induced Rats

Abstract

Antioxidants present in food can act as a protective factor against the development of colorectal cancer (CRC) by reducing the development of aberrant crypt foci (ACF). This study aimed to analyze the effects of supplementation with juçara fruit pulp on the number of ACF and the SOD1 expression in an experimental model of CRC. Colorectal carcinogenesis was induced with 1,2-dimethylhydrazine (DMH) in 16 young female rats (Rattus norvegicus) given a diet supplemented with either juçara fruit pulp (DMH+/juçara+) or control (DMH+/juçara–). Five animals were used as a negative control (DMH–/juçara–). The (DMH+/juçara+) group received 14?days of supplementation (100?ml/animal/day) at 2-day intervals for 1 month. The number of ACF, area of positive staining for SOD1, and SOD1 expression score were evaluated. The (DMH+/juçara+) group presented a lower number of ACF, ACF > 3 crypts, and greater SOD1 expression in the colorectal mucosa. Based on the reduction in the number of lesions and possible positive impact on antioxidant enzymes, juçara fruit pulp appears to support the prevention of CRC, opening new possibilities for its use in dietary supplementation, as well as in the development of products and medications for the prevention and treatment of CRC.     

The Development of Thermal Nanoprobe Methods as a Means of Characterizing and Mapping Plasticizer Incorporation into Ethylcellulose Films

Purpose

The phase composition and distribution of ethylcellulose (EC) films containing varying amounts of the plasticizer fractionated coconut oil (FCO) were studied using a novel combination of thermal and mapping approaches.

Methods

The thermal and thermomechanical properties of films containing up to 30% FCO were characterized using modulated temperature differential scanning calorimetry (MTDSC) and dynamic mechanical analysis (DMA). Film surfaces were mapped using atomic force microscopy (AFM; topographic and pulsed force modes) and the composition of specific regions identified using nanothermal probes.

Results

Clear evidence of distinct conjugate phases was obtained for the 20?C30% FCO/EC film systems. We suggest a model whereby the composition of the distinct phases may be estimated via consideration of the glass transition temperatures observed using DSC and DMA. By combining pulsed force AFM and nano-thermal analysis we demonstrate that it is possible to map the two separated phases. In particular, the use of thermal probes allowed identification of the distinct regions via localized thermomechanical analysis, whereby nanoscale probe penetration is measured as a function of temperature.

Conclusion

The study has indicated that by using thermal and imaging techniques in conjunction it is possible to both identify and map distinct regions in binary films.     

Use of polar organic chemical integrative samplers to assess the effects of chronic pesticide exposure on biofilms

The responses of aquatic organisms to chronic exposure to environmental concentrations of toxicants, often found in mixtures, are poorly documented. Here passive sampler extracts were used in experimental contamination of laboratory channels, to investigate their effects on natural biofilm communities. A realistic mixture of pesticides extracted from Polar Organic Chemical Integrative Samplers was used to expose biofilms in laboratory channels to total pesticide concentrations averaging 0.5 ± 0.1 μg l^?1. The level of exposure was representative of field conditions in terms of relative proportions of the substances but the exposure concentration was not maintained (decreasing concentrations between contamination occasions). The impact on the structural as well as the functional characteristics of the autotrophic and heterotrophic components was determined, using biofilm grown in uncontaminated conditions (reference site) and in sites exposed to pesticides (contaminated site). The exposure imposed did not significantly modify the structure or functions of reference biofilms, nor did it modify tolerance as measured by mixture EC₅₀ (EC₅₀ mix). In contrast, the communities from the more contaminated downstream section lost tolerance following decreased dose exposure, but community composition remained fairly stable. Overall, these results indicate that low levels of contamination did not lead to strong changes in community structure, and 14-day changes in tolerance seemed to depend mainly on physiological adaptation, suggesting that other environmental factors or longer-lasting processes prevailed. This study reports the first attempt to use passive sampler extracts as a realistic composite contaminant for experimental exposure of biofilms, with promising perspectives in further ecotoxicology studies.     

The ecological risk of heavy metals in sediment from the Danube Delta

The objectives of this study were to assess the sediment contamination with heavy metals and to investigate accordingly the ecological risk posed in the SE of the Danube Delta. Sediments are important in assessing the contamination as they act as reservoirs, transporters and contamination sources. Sediment samples were collected and analysed for lead, cadmium, arsenic and mercury, revealing levels higher than the background, especially for cadmium and mercury (Pb > As > Cd > Hg). Concentrations exceeding the probable effect limit were noticed for arsenic and mercury. The contamination indexes describe the study area as having almost half of the samples as contaminated (pollution load index-PLI 1.04), however the contamination is mostly low-to moderate (modified contamination degree-mCd 1.36). The sediment contamination poses mostly a low ecological risk (RI 94.8). The sediment quality guideline quotient (SQG-Q 0.29) describes a moderate impact, while the probable effect concentration quotient (PEC-Q 0.16) confirms that there are no levels likely to affect the aquatic biota. In our study area, the main Branch of the Danube River and the Secondary Delta are the most affected by contamination, while the narrow, reed abundant channels as the preferred habitat of most aquatic organisms, have a low contamination level.     

Treating <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> infections in an intensive care unit at a University Hospital in Brazil

Background Optimizing antimicrobial therapy is important for treating patients who are critically ill with Staphylococcus aureus infection, and susceptibility tests are necessary. Objective The aim of the present study was to evaluate antibacterial therapy after susceptibility testing of S. aureus infections. Setting The setting was an intensive care unit at a University Hospital in Brazil. Methods An observational and retrospective study was conducted over 6 years. The antimicrobials that were used for S. aureus infection treatment were calculated as the defined daily dose per 1000 patient-days (DDD₁₀₀₀). Antimicrobial susceptibility data were obtained by reviewing bacteriological tests. Patient profiles and treatment were determined by analyzing patient charts. Results Methicillin-resistant S. aureus (MRSA) was prevalent in this study (76.13 %). Patients who were infected with MRSA had total antimicrobial consumption that was three-times higher (9567.2 DDD₁₀₀₀) than patients who were infected with methicillin-susceptible S. aureus (MSSA; 3101.1 DDD₁₀₀₀). The average length of stay in the intensive care unit was 19 days (interquartile range 17 days) for MSSA and 20 days (interquartile range 20 days) for MRSA. Mortality in patients who were infected with MSSA was higher (52.17 %) than in patients who were infected with MRSA (33.80 %), and de-escalation was not identified in 73.90 % of MSSA patients.     

Synthesis and Physicochemical Characterization of a Diethyl Ester Prodrug of DTPA and Its Investigation as an Oral Decorporation Agent in Rats

The increasing threats of nuclear terrorism have made the development of medical countermeasures a priority for international security. Injectable formulations of diethylenetriaminepentaacetic acid (DTPA) have been approved by the FDA; however, an oral formulation is more amenable in a mass casualty situation. Here, the diethyl ester of DTPA, named C2E2, is investigated for potential as an oral treatment for internal radionuclide contamination. C2E2 was synthesized and characterized using NMR, MS, and elemental analysis. The physiochemical properties of solubility, lipophilicity, and stability were investigated in order to predict its oral bioavailability. Finally, an animal efficacy study was conducted in Sprague Dawley rats pre-contaminated by intramuscular injection with ²⁴¹Am(NO₃)₃ to establish effectiveness of the therapy via the oral route. Synthesis of C2E2 yielded a crystalline powder with high solubility and improved lipophilicity over DTPA. The ester was stable in both simulated gastric and intestinal fluids over the anticipated time course of absorption. Capsules containing C2E2 were demonstrated to be stable for 12 months under accelerated stability conditions. After a single dose, C2E2 enhanced the elimination of ²⁴¹Am in a dose-dependent manner. Significant improvement was seen in both total ²⁴¹Am decorporation and reduction of ²⁴¹Am liver and skeletal burden. C2E2 was concluded to be effective when orally administered to ²⁴¹Am-contaminated rats. It may therefore have potential for medical countermeasure in treating humans contaminated with ²⁴¹Am or other transuranic elements. An oral capsule or powder for reconstitution may be suitable formulations for future development based on the physiochemical properties and anticipated dose required for efficacy.