Retrospective Correlation between First Drug Treatment Duration and Survival Outcomes in Sequential Treatment with Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: A Real-World Subgroup Analysis.

Background: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially. Patients and Methods: The study involved thirteen Italian cancer centers on a 10-year retrospective observation (2012-2022). In this subgroup analysis, we focused our attention on the correlation between the first drug treatment duration (<3 months, 3 to <6 months and ≥6 months) and survival outcomes in patients who had received the sequence regorafenib-to-trifluridine/tipiracil, or vice versa. Results: The initial study included 866 patients with mCRC who received sequential T/R, or R/T, or T or R alone. This analysis is focused on evaluating the impact of the duration of the first treatment in the sequence on clinical outcomes (OS, PFS) and includes 146 and 116 patients of the T/R and R/T sequences, respectively. Based on the duration of the first drug treatment, subgroups for the T/R sequence included 27 patients (18.4%) who received T for <3 months, 86 (58.9%) treated for 3 to <6 months, and 33 (22.6%) treated for ≥6 months; in the reverse sequence (R as the first drug), subgroups included 18 patients (15.5%) who received their first treatment for <3 months, 62 (53.4%) treated for 3 to <6 months, and 35 (31.0%) treated for ≥6 months. In patients who received their first drug treatment for a period of 3 to <6 months, the R/T sequence had a significantly longer median OS (13.7 vs. 10.8 months, p = 0.0069) and a longer median PFS (10.8 vs. 8.5 months, p = 0.0003) than the T/R group. There were no statistically significant differences between groups with first drug treatment durations of <3 months and ≥6 months. Conclusions: Our analysis seems to suggest that the administration of R for a period of 3 to <6 months before that of T can prolong both OS and PFS, as compared to the opposite sequence.

Treatment Settings and Outcomes with Regorafenib and Trifluridine/Tipiracil at Third-Line Treatment and beyond in Metastatic Colorectal Cancer: A Real-World Multicenter Retrospective Study.

BACKGROUND: Patients with refractory mCRC rarely undergo third-line or subsequent treatment. This strategy could negatively impact their survival. In this setting, regorafenib (R) and trifluridine/tipiracil (T) are two key new treatment options with statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control with different tolerance profiles. This study aimed to retrospectively evaluate the efficacy and safety profiles of these agents in real-world practice. MATERIALS AND METHODS: In 2012-2022, 866 patients diagnosed with mCRC who received sequential R and T (T/R, n = 146; R/T, n = 116]) or T (n = 325]) or R (n = 279) only were retrospectively recruited from 13 Italian cancer institutes. RESULTS: The median OS is significantly longer in the R/T group (15.9 months) than in the T/R group (13.9 months) (p = 0.0194). The R/T sequence had a statistically significant advantage in the mPFS, which was 8.8 months with T/R vs. 11.2 months with R/T (p = 0.0005). We did not find significant differences in outcomes between groups receiving T or R only. A total of 582 grade 3/4 toxicities were recorded. The frequency of grade 3/4 hand-foot skin reactions was higher in the R/T sequence compared to the reverse sequence (37.3% vs. 7.4%) (p = 0.01), while grade 3/4 neutropenia was slightly lower in the R/T group than in the T/R group (66.2% vs. 78.2%) (p = 0.13). Toxicities in the non-sequential groups were similar and in line with previous studies. CONCLUSIONS: The R/T sequence resulted in a significantly longer OS and PFS and improved disease control compared with the reverse sequence. R and T given not sequentially have similar impacts on survival. More data are needed to define the best sequence and to explore the efficacy of sequential (T/R or R/T) treatment combined with molecular-targeted drugs.

The Effect of Message Framing in Promoting the Mediterranean Diet: The Moderating Role of Eating Self-Efficacy.

Although a Mediterranean diet (MeDiet) provides several psychophysical health benefits, research on how to effectively promote MeDiet adherence is still lacking. In the present study, we tested the effectiveness of a messaging intervention aimed at promoting the adherence to the Mediterranean diet. A total of 435 Italian participants responded to a questionnaire on their eating self-efficacy and adherence to the MeDiet at Time 1. Then, participants were randomly assigned to three different conditions: (a) gain messages focused on the positive outcomes of MeDiet adherence; (b) non-loss messages focused on the avoided negative outcomes associated with MeDiet adherence; (c) no messages (control). After the 2 week intervention, participants answered some questions regarding their perception of threat and distress, evaluation of the messages, and adherence to the MeDiet at Time 2. We also tested whether the messaging intervention influenced participants' MeDiet adherence at Time 2. Results confirmed that the messaging intervention enhanced the MeDiet adherence (F(2,432) = 4.61; p = 0.01, ηp2 = 0.02), with no difference between exposure to gain or non-loss messages (95% LLCI = -0.32; 95% ULCI = 0.54). We then tested whether message framing effectiveness was influenced by eating self-efficacy, and results showed that gain messages were more persuasive for participants with low eating self-efficacy (effect size = 0.01; p for interaction = 0.03). Discussion suggests that tailoring messages according to receivers' psychological characteristics seems to be pivotal to enhance the persuasiveness of messages aimed at promoting the MeDiet adherence.

The Influence of Message Framing on Consumers' Selection of Local Food.

Although local food purchasing provides several benefits to both consumers and producers, research on what recommendation messages can effectively promote the purchase of local food is still lacking. In the present study, 410 participants were involved in a 2-week intervention relying on prefactual (i.e., "If … then") messages promoting the purchase of local food. All messages were sent through a research app to participants' mobile phones and were focused on environmental consequences of purchasing (or not purchasing) local food. Four experimental conditions involving messages differing as to outcome sensitivity framing (i.e., gain, non-loss, non-gain and loss) were compared to a control condition. To test the effectiveness of the messages, before and after the 2-week intervention participants were involved in a choice task. They were asked to choose among fruits with different provenience, that is, from the participants' municipality of residence or abroad. Results showed that all message frames increased the selection of local food, compared to control. Furthermore, pro-environmental consumers were more persuaded by messages formulated in terms of gains and non-gains, whereas healthy consumers were more persuaded by messages formulated in terms of losses or non-losses. Discussion focuses on the advantages of tailored communication to promote the purchase of local food.

The Psychosocial Antecedents of the Adherence to the Mediterranean Diet.

OBJECTIVE: Most previous research on the antecedents of healthy food choice has not investigated the links between these antecedents and has focused on specific food choice rather than on an overall diet. In the present study, we tested the plausibility of an integrated theoretical model aiming to explain the role of different psychosocial factors in increasing the intention to adhere to the Mediterranean Diet (MeDiet). DESIGN AND PARTICIPANTS: A sample of 1940 Italian adults participated in an online survey that measured their attitude and perceived behavioral control (i.e., rational antecedents), subjective norm (i.e., social antecedent), positive and negative anticipated emotions (i.e., emotional antecedents), food choice health and mood motives (i.e., motivational antecedents), past adherence to the MeDiet (i.e., behavioral antecedent), and the intention to adhere to the MeDiet. RESULTS: Structural Equation Modelling (SEM) analyses confirmed the plausibility of the proposed model. Perceived behavioral control was the strongest rational antecedent of intention, followed by the emotional (i.e., anticipated emotions) and the social (i.e., subjective norm) antecedents. Mediation analysis showed that motivational antecedents had only an indirect impact on intention via emotional antecedents. Finally, multigroup SEM analysis highlighted that past adherence to the MeDiet moderated the hypothesized paths among all the study variables. CONCLUSIONS: The above findings advance our comprehension of which antecedents public communication might leverage to promote an increase in the adherence to the MeDiet.

Regorafenib-to-trifluridine/tipiracil Versus the Reverse Sequence for Refractory Metastatic Colorectal Cancer Patients: A Multicenter Retrospective Real-life Experience.

BACKGROUND/AIM: Regorafenib (REG) and trifluridine/tipiracil (FTD/TPI) have have been shown to improve overall survival in patients with refractory metastatic colorectal cancer. The aim of our study was to evaluate the efficacy and safety profiles of these agents administered in sequence in real world practice. PATIENTS AND METHODS: Clinical data of patients treated beyond the 2°line with REG or FTD/TPI between January 2016 and August 2020, were retrospectively collected from eight institutes in the Lazio Region. RESULTS: We included 49 patients treated with both drug sequences. A total of 28 G3/G4 toxicity events (53.8%) were recorded in the FTD/TPI-to-REG sequence vs. 24 (46.1%) in the reverse sequence. Median overall survival for the patients included in the FTP/TPI-to-REG group was 20 months (95%CI=16.7-23.3) vs. 27 months in the reverse group (95%CI=17.8-36.2). The disease control rate was 45.0% for patients treated with the REG-to-FTD/TPI sequence vs. 24.1% in those treated with the FTD/TPI-to-REG sequence (p=0.18). CONCLUSION: The sequence REG-to-FTD/TPI and vice versa can extend survival, whereas only REG-to-FTD/TPI stabilizes cancer growth.

Source proximity and meteorological effects on residential outdoor VOCs in urban areas: Results from the Houston and Los Angeles RIOPA studies.

Concentrations of volatile organic compounds (VOCs) measured outside homes in Houston, TX and Los Angeles, CA were characterized by the effects of source proximity and meteorological factors. Benzene, toluene, ethylbenzene, m,p-xylene, o-xylene (BTEX), methyl tert butyl ether (MTBE), tetrachloroethylene (perchloroethylene, PCE), and carbon tetrachloride (CCl4) were examined. Multiple stepwise regression analysis converged the best-fit models with predictors from meteorological conditions and the proximity to specific point, area, and mobile sources on the residential outdoor VOC concentrations. Negative associations of wind speed with concentrations demonstrated the effect of dilution by high wind speed. Atmospheric stability increase was associated with concentration increase. Petrochemical source proximity was a significant predictor for BTEX and MTBE concentrations in Houston. Ethylbenzene and xylene source proximity was a significant predictor in Los Angeles. Close proximity to area sources such as scrap metal recycling or dry cleaning facilities increased the MTBE, PCE, and CCl4 concentrations in Houston and Los Angeles. Models for ethylbenzene, m,p-xylene, and MTBE in Houston, and benzene in Los Angeles explained that for the median values of the meteorological factors, homes closest to influential highways would have concentrations that were 1.7-2.2 fold higher than those furthest from these mobile emission sources. If the median distance to sources were used in the models, the VOC concentrations varied 1.7 to 6.6 fold as the meteorological conditions varied over the observed range. These results highlight that each urban area is unique and localized sources need to be carefully evaluated to understand potential contributions to VOC air concentrations near residences, which influence baseline indoor air concentrations and personal exposures. Results of this study could assist in the appropriate design of monitoring networks for community-level sampling. They may also improve the accuracy of exposure models linking emission sources with estimated pollutant concentrations at the residential level.

Wood smoke risk assessment: defining the questions.

Risk assessment provides a framework for combining and evaluating scientific data on source-to-health effects for contaminants that could potentially affect the health of human populations. It utilizes an integrated approach to hazard identification, dose response, exposure assessment, and risk characterization. Since the range of potential exposure scenarios is considerable, given the complexity of wood-smoke sources and emissions, there is a need for defining the critical characteristics for the key parameters leading to adverse health outcomes. During the International Biomass Smoke and Health Effects (IBSHE) conference at the University of Montana (August 2007), the breakout group entitled "Risk Assessment: Defining the Questions" was tasked with evaluating the current state of the science in regard to risk assessment involving biomass smoke exposure. As a result of these discussions, important data gaps and future research questions were identified that are reported in this article.

Cancer risk disparities between hispanic and non-hispanic white populations: the role of exposure to indoor air pollution.

BACKGROUND: Hispanics are the fastest growing minority group in the United States; however, minimal information is available on their cancer risks from exposures to hazardous air pollutants (HAPs) and how these risks compare to risks to non-Hispanic whites. METHODS: We estimated the personal exposure and cancer risk of Hispanic and white adults who participated in the Relationships of Indoor, Outdoor, and Personal Air (RIOPA) study. We evaluated 12 of the sampled volatile organic compounds and carbonyls and identified the HAPs of most concern and their possible sources. Furthermore, we examined sociodemographic factors and building characteristics. RESULTS: Cumulative cancer risks (CCRs) estimated for Hispanics (median = 519 x 10(-6), 90th percentile = 3,968 x 10(-6)) and for whites (median = 443 x 10(-6), 90th percentile = 751 x 10(-6)) were much greater than the U.S. Environmental Protection Agency (EPA) benchmark of 10(-6). Cumulative risks were dominated by formaldehyde and p-dichlorobenzene (p-DCB) and, to a lesser extent, by acetaldehyde, chloroform, and benzene. Exposure to all of these compounds except benzene was primarily due to indoor residential sources. Hispanics had statistically higher CCRs than did whites (p

Evaluation of the use of diffusive air samplers for determining temporal and spatial variation of volatile organic compounds in the ambient air of urban communities.

The Houston-Galveston metropolitan area has a relatively high density of point and mobile sources of air toxics, and determining and understanding the relationship between emissions and ambient air concentrations of air toxics is important for evaluating potential impacts on public health and formulating effective regulatory policies to control this impact, both in this region and elsewhere. However, conventional ambient air monitoring approaches are limited with regard to expense, siting limitations, and representative sampling necessary for adequate exposure assessment. The overall goal of this multiphase study is to evaluate the use of simple passive air samplers to determine temporal and spatial variability of the ambient air concentrations of selected volatile organic compounds (VOCs) in urban areas. Phase 1 of this study, reported here, was a field evaluation of 3M organic vapor monitors (OVMs) involving limited comparisons with commonly used active sampling methods, an assessment of sampler precision, a determination of optimal sampling duration, and an investigation of the utility of a simple modification of the commercial sampler. The results indicated that a sampling duration of 72 hr exhibited generally low bias relative to automated continuous gas chromatography measurements, good overall precision, and an acceptable number of measurements above detection limits. The modified sampler showed good correlation with the commercial sampler, with higher sampling rates, although lower than expected.

Passive dosimeters for nitrogen dioxide in personal/indoor air sampling: a review.

Accurate measurement of nitrogen dioxide concentrations in both outdoor and indoor environments, including personal exposures, is a fundamental step for linking atmospheric nitrogen dioxide levels to potential health and ecological effects. The measurement has been conducted generally in two ways: active (pumped) sampling and passive (diffusive) sampling. Diffusion samplers, initially developed and used for workplace air monitoring, have been found to be useful and cost-effective alternatives to conventional pumped samplers for monitoring ambient, indoor and personal exposures at the lower concentrations found in environmental settings. Since the 1970s, passive samplers have been deployed for ambient air monitoring in urban and rural sites, and to determine personal and indoor exposure to NO2. This article reviews the development of NO2 passive samplers, the sampling characteristics of passive samplers currently available, and their application in ambient and indoor air monitoring and personal exposure studies. The limitations and advantages of the various passive sampler geometries (i.e., tube, badge, and radial type) are also discussed. This review provides researchers and risk assessors with practical information about NO2 passive samplers, especially useful when designing field sampling strategies for exposure and indoor/outdoor air sampling.

Relationships of Indoor, Outdoor, and Personal Air (RIOPA): part II. Analyses of concentrations of particulate matter species.

During the study Relationships of Indoor, Outdoor, and Personal Air (RIOPA*), 48-hour integrated indoor, outdoor, and personal air samples were collected between summer 1999 and spring 2001 in three different areas of the United States: Elizabeth NJ, Houston TX, and Los Angeles County CA. Air samples suitable for analyzing particulate matter 2.5 microm or smaller in aerodynamic diameter (PM2.5) were collected in 219 homes (twice in 169 homes). Indoor and outdoor air samples suitable for gas-phase and particle-phase organic analyses were collected in 152 homes (twice in 132 homes). Samples or subsets of samples were analyzed for PM2.5 mass, organic functional groups, elements, organic carbon (OC), elemental carbon (EC), gas-phase and particle-phase polycyclic aromatic hydrocarbons (PAHs), and chlordanes. Air exchange rate (AER), temperature, and relative humidity were measured for each residence; questionnaire data and time-activity information were collected from the participants. Median indoor, outdoor, and personal PM2.5 mass concentrations were 14.4, 15.5, and 31.4 microg/m3, respectively. Personal PM2.5 concentrations were significantly higher and more variable than indoor and outdoor concentrations. Several approaches were applied to quantify indoor PM2.5 of ambient (outdoor) and nonambient (indoor) origin, some using PM2.5 mass concentrations and others using PM2.5 species concentrations. PM of outdoor origin was estimated in three ways using increasingly accurate assumptions. Comparing estimates from the three approaches enabled us to quantify several types of errors that may be introduced when central-site PM concentrations are used as surrogate estimates for PM exposure. Estimates made using individual measurements produced broader distributions and higher means than those made using a single infiltration factor for all homes and days. The best estimate (produced by the robust regression approach) of the mean contribution of outdoor PM2.5 to the indoor mass concentration was 73% and to personal exposure was 26%. Possible implications of exposure error for epidemiologic assessments of PM are discussed below. Organic particulate matter was the major constituent of PM2.5 generated indoors. After correcting for artifacts, it constituted 48%, 55%, and 61% of PM2.5 mass inside study homes in Los Angeles, Elizabeth, and Houston, respectively. At least 40% but probably closer to 75% of this organic matter, on average, was emitted or formed indoors. Functional group analysis provided some insights into the composition and properties of the indoor-generated organic PM2.5. Chlordane, a very minor but mutagenic semivolatile organic mixture previously used as a termiticide, was found to be mostly of indoor origin. High emission rates were most frequently found in homes built from 1945 to 1959. Analysis of the change in gas-particle partitioning during transport of outdoor PAHs to indoor environments illustrated that chemical thermodynamics can alter the concentration and composition of outdoor PM as it is transported indoors. (This has been previously noted for nitrate [Lunden et al 2003].) In epidemiologic studies that rely on central-site monitoring data, such transformations may result in measurement error, and this possibility warrants further investigation.

How does infiltration behavior modify the composition of ambient PM2.5 in indoor spaces? An analysis of RIOPA data.

The indoor environment is an important venue for exposure to fine particulate matter (PM2.5) of ambient (outdoor) origin. In this work, paired indoor and outdoor PM2.5 species concentrations from three geographically distinct cities (Houston, TX, Los Angeles County, CA, and Elizabeth, NJ) were analyzed using positive matrix factorization (PMF) and demonstrate that the composition and source contributions of ambient PM2.5 are substantially modified by outdoor-to-indoor transport. Our results suggest that predictions of "indoor PM2.5 of ambient origin" are improved when ambient PM2.5 is treated as a combination of four distinct particle types with differing infiltration behavior (primary combustion, secondary sulfate and organics, secondary nitrate, and mechanically generated PM) rather than as a "single internally mixed entity". Study-wide average infiltration factors (i.e., fraction of ambient PM2.5 found indoors) for Relationship of Indoor, Outdoor, and Personal Air (RIOPA) study homes were 0.51, 0.78, and 0.04 (consistent with P = 0.6, 0.9, and 0.09; k = 0.2, 0.1, and 0.6 h(-1)) for PM2.5 associated with primary combustion, secondary formation (excluding nitrate), and mechanical generation, respectively. Modification of the composition, properties, and source contributions of ambient PM2.5 in indoor environments has important implications for exposure mitigation strategies, development of health hypotheses, and evaluation of exposure error in epidemiological studies that use ambient central-site PM2.5 as a surrogate for PM2.5 exposure.

Estimating volatile organic compound concentrations in selected microenvironments using time-activity and personal exposure data.

Repeated measures of personal exposure to 14 volatile organic compounds (VOC) were obtained over 3 seasons for 70 healthy, nonsmoking adults living in Minneapolis-St. Paul. Matched data were also available for participants' time-activity patterns, and measured VOC concentrations outdoors in the community and indoors in residences. A novel modeling approach employing hierarchical Bayesian techniques was used to estimate VOC concentrations (posterior mode) and variability (credible intervals) in five microenvironments: (1) indoors at home; (2) indoors at work/school; (3) indoors in other locations; (4) outdoors in any location; and (5) in transit. Estimated concentrations tended to be highest in "other" indoor microenvironments (e.g., grocery stores, restaurants, shopping malls), intermediate in the indoor work/school and residential microenvironments, and lowest in the outside and in-transit microenvironments. Model estimates for all 14 VOC were reasonable approximations of measured median concentrations in the indoor residential microenvironment. The largest predicted contributor to cumulative (2-day) personal exposure for all 14 VOC was the indoor residential environment. Model-based results suggest that indoors-at-work/school and indoors-at-other-location microenvironments were the second or third largest contributors for all VOC, while the outside-in-any-location and in-transit microenvironments appeared to contribute negligibly to cumulative personal exposure. Results from a mixed-effects model indicate that being in or near a garage increased personal exposure to o-xylene, m/p-xylene, benzene, ethylbenzene, and toluene, and leaving windows and doors at home open for 6 h or more decreased personal exposure to 13 of 14 VOC, all except trichloroethylene.

Concentrations and source characteristics of airborne carbonyl compounds measured outside urban residences.

This paper presents the analysis of ambient air concentrations of 10 carbonyl compounds (aldehydes and ketones) measured in the yards of 87 residences in the city of Elizabeth, NJ, throughout 1999-2001. Most of these residences were measured twice in different seasons; the sampling duration was 48 hr each time. The authors observed higher concentrations for most of the measured carbonyl compounds on warmer days, reflecting larger contributions of photochemical reactions on warmer days. The estimated contributions of photochemical production varied substantially across the measured carbonyl compounds and could be as high as 60%. Photochemical activity, however, resulted in a net loss for formaldehyde. The authors used stepwise multiple linear regression models to evaluate the impact of traffic sources and meteorological conditions on carbonyl concentrations using the data collected on colder days (with lower photochemical activities). They found that the concentrations of formaldehyde, acetaldehyde, acrolein, propionaldehyde, crotonaldehyde, benzaldehyde, glyoxal, and methylglyoxal significantly decreased with increasing distance between a measured residence and one or more major roadways. They also found significant negative associations between concentrations for most of the measured carbonyl compounds and each of the following meteorological parameters: mixing height, wind speed, and precipitation.

Source proximity and outdoor-residential VOC concentrations: results from the RIOPA study.

Ambient volatile organic compound concentrations outside residences were measured in Elizabeth, New Jersey as part of the Relationship of Indoor, Outdoor, and Personal A:r (RIOPA) study to assess the influence of proximity of the residences to known ambient emissions sources. The closest distances between the outdoor samplers and emission sources were determined using Geographic Information Systems (GIS)techniques. Multiple regression models were developed for residential ambient concentrations of aromatic hydrocarbons (BTEX), methyl tert butyl ether (MTBE), and tetrachloroethylene (PCE). The natural log transformed ambient concentrations of BTEX were inversely associated with distances to major roadways with high traffic densities and gasoline stations, atmospheric stability, temperature, and wind speed. Ambient MTBE levels were associated with inverse distance to gas stations and interstate highways. Residential ambient PCE concentration was inversely associated with distance to dry cleaning facilities, atmospheric stability, temperature, wind speed, and relative humidity. The linear regression models that include proximity to emission sources and meteorological variables explained 16-45% of the overall variation of ambient residential VOC concentrations. Meteorological conditions, especially atmospheric stability and temperature, explained 60-90% of the total variation in the regression models. The residential ambient air concentrations were 1.5-4 times higher than the urban background levels outside homes very close (<50 m) to ambient emission sources where approximately 7% of the population live. However, the relative increase of risk for disease is small and variations in air concentration in the background urban atmosphere are greater than those from the proximity to roadways.

Fine organic particulate matter dominates indoor-generated PM2.5 in RIOPA homes.

Residential indoor and outdoor fine particle (PM(2.5)) organic (OC) and elemental carbon (EC) concentrations (48 h) were measured at 173 homes in Houston, TX, Los Angeles County, CA, and Elizabeth, NJ as part of the Relationship of Indoor, Outdoor and Personal Air (RIOPA) study. The adsorption of organic vapors on the quartz fiber sampling filter (a positive artifact) was substantial indoors and out, accounting for 36% and 37% of measured OC at the median indoor (8.2 microg C/m(3)) and outdoor (5.0 microg C/m(3)) OC concentrations, respectively. Uncorrected, adsorption artifacts would lead to substantial overestimation of particulate OC both indoors and outdoors. After artifact correction, the mean particulate organic matter (OM=1.4 OC) concentration indoors (9.8 microg/m(3)) was twice the mean outdoor concentration (4.9 microg/m(3)). The mean EC concentration was 1.1 microg/m(3) both indoors and outdoors. OM accounted for 29%, 30% and 29% of PM(2.5) mass outdoors and 48%, 55% and 61% of indoor PM(2.5) mass in Los Angeles Co., Elizabeth and Houston study homes, respectively. Indirect evidence provided by species mass balance results suggests that PM(2.5) nitrate (not measured) was largely lost during outdoor-to-indoor transport, as reported by Lunden et al. This results in dramatic changes with outdoor-to-indoor transport in the mass and composition of ambient-generated PM(2.5) at California homes. On average, 71% to 76% of indoor OM was emitted or formed indoors, calculated by (1) Random Component Superposition (RCS) model and (2) non-linear fit of OC and air exchange rate data to the mass balance model. Assuming that all particles penetrate indoors (P=1) and there is no particle loss indoors (k=0), a lower bound estimate of 41% of indoor OM was indoor-generated (mean). OM appears to be the predominant species in indoor-generated PM(2.5), based on species mass balance results. Particulate OM emitted or formed indoors is substantial enough to alter the concentration, composition and behavior of indoor PM(2.5). One interesting effect of increased indoor OM concentrations is a shift in the gas-particle partitioning of polycyclic aromatic hydrocarbons (PAHs) from the gas to the particle phase with outdoor-to-indoor transport.

Long-term moxifloxacin in complicated tuberculosis patients with adverse reactions or resistance to first line drugs.

STUDY OBJECTIVES: To test safety and tolerability of long-term moxifloxacin in resistant tuberculosis (TB) patients and patients with intolerance to first line anti-TB drugs. DESIGN: Clinical evaluation of adverse events (AEs) during prolonged moxifloxacin treatment. SETTING: TB Unit of the Regional TB Reference Center, Villa Marelli Institute, Niguarda Ca'Granda Hospital, Milan, Italy PATIENTS AND INTERVENTIONS: Patients treated with moxifloxacin, 400 mg orally once daily for TB in the Villa Marelli Institute from January 2001 to December 2003 were enrolled. RESULTS: Thirty-eight patients were treated with moxifloxacin at the Villa Marelli Institute in the study period, for multidrug resistant (MDR) TB (14, 36.8%), for intolerance to first line anti-TB drugs (9, 23.7%), for combined resistance and intolerance to first line anti-TB drugs (12, 31.6%), other reasons (3, 7.9%). The mean duration of moxifloxacin treatment was 6.3 +/- 5.2 months. Twelve (31.6%) patients reported at least an AE due to moxifloxacin, mostly gastrointestinal (8, 21.0%), general (5, 13.2%) and central nervous system (3, 7.9%) AEs. In 4 (10.5%) patients the drug was withdrawn for major AEs; no irreversible or fatal events were recorded. Most of the patients (31, 81.6%) reported a treatment success, even if the success rate was lower in MDR TB patients (8/14, 51.7%). CONCLUSIONS: Despite the fact that a large proportion of patients experienced at least an AE due to moxifloxacin, the drug resulted safe in the long-term administration for complicated TB cases.

Nanoparticle-induced platelet aggregation and vascular thrombosis.

Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2-300 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 microm). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN>or=SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.

Exposure assessment in the National Children's Study: introduction.

The science of exposure assessment is relatively new and evolving rapidly with the advancement of sophisticated methods for specific measurements at the picogram per gram level or lower in a variety of environmental and biologic matrices. Without this measurement capability, environmental health studies rely on questionnaires or other indirect means as the primary method to assess individual exposures. Although we use indirect methods, they are seldom used as stand-alone tools. Analyses of environmental and biologic samples have allowed us to get more precise data on exposure pathways, from sources to concentrations, to routes, to exposure, to doses. They also often allow a better estimation of the absorbed dose and its relation to potential adverse health outcomes in individuals and in populations. Here, we make note of various environmental agents and how best to assess exposure to them in the National Children's Study--a longitudinal epidemiologic study of children's health. Criteria for the analytical method of choice are discussed with particular emphasis on the need for long-term quality control and quality assurance measures.