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Estimation of population pharmacokinetic parameters using destructively obtained experimental data: a simulation study of the one-compartment open model.

A simulation study of the one-compartment open pharmacokinetic model has been made. The population pharmacokinetic parameters which characterize the population of drug residues over time are assumed to be stochastic. A general theoretical model framework for parameter estimation via the method of extended least squares is presented. Formulas approximating the required mean and variance time functions are developed and subsequently used in the simulation study. The effects of four different designs in four different animal populations are presented. The simulated data are those of the single observation per animal per time point type. The characterizing population pharmacokinetic parameters have been analyzed for bias and reliability in both a naive and second-order mean model. Recommendations for choosing an appropriate sampling design are included.

Analysis of Variance↗

On-line analysis of the size distribution of fine and ultrafine aerosol particles in flue and stack gas of a municipal waste incineration plant: effects of dynamic process control measures and emission reduction devices.

The size distribution of particles in the waste gas of a municipal waste incineration plant (23 MW) was measured on-line at two sampling points in the flue-gas duct (700 and 300 degrees C) as well as in the stack gas (80 degrees C). The measurements were performed during both stable combustion conditions and transient operating conditions. The particle measurements were carried out by a mobile system consisting of a home-designed sampling system with dilution device and a scanning mobility particle sizer (SMPS) for the particle size range 17-600 nm as well as an aerodynamic particle sizer (APS) for the size range 500 nm-30 microm. The APS and SMPS data were combined using a special method and a home written software tool. The maximum of the particle-size distribution in the flue gas of the incinerator shifts from about 90 nm at the 700 degrees C sampling point to about 140 nm at the 300 degrees C point, showing the particle growth by coagulation processes and condensation of inorganic and organic gaseous species with decreasing temperature. This finding is consistent with the measured concentration profiles of gaseous organic chemical species in the flue gas. While at flue-gas temperatures of 600-800 degrees C a rich pattern of polycyclic aromatic hydrocarbon species (PAH) is observable, the PAH concentrations are considerably reduced further downstream of the flue-gas channel, where the temperature drops below 500 degrees C. Condensation and reactive bonding of gaseous chemicals onto particulate matter is, among other reasons, responsible for the depletion of gas-phase species. Process control measures, such as firing the backup burners or cleaning of the grate with pressurized air, can cause dynamic changes of the particle-size distribution. Furthermore the flue-gas cleaning measures have great impact onto both the particle concentration and the size distribution. For this reason the impact of one particular emission reduction device, the wet electrostatic dust precipitator (wet-ESP), is evaluated. The wet-ESP reduces considerably the particle concentration over the whole size range. Behind the flue-gas processing units a broad maximum in the particle-size distribution occurs at about 70 nm, but no pronounced particle-size distribution could be observed. The particle concentration level atthis maximum is about 3 magnitudes lower than in the raw flue gas. However, intermittent periods lasting for several minutes of high emissions of ultrafine particles with d < 40 nm were observed. These particles are most likely formed by nucleation processes behind the wet-ESP from gas-phase constituents of the stack gas.

Aerosols↗

Psychiatric symptoms and quality of life in schizophrenia: a meta-analysis.

Quality of life (QoL) has been recognized as an important outcome of schizophrenia treatment, yet the determinants of QoL for individuals with schizophrenia are not well known. Research has consistently found psychiatric symptoms to be negatively related to QoL, however, findings concerning the strength of these relationships have been mixed, making it difficult to determine the degree to which such symptoms are related to poor QoL. This research presents a systematic meta-analysis of studies examining the relationship between psychiatric symptoms and QoL in schizophrenia, in an effort to elucidate the determinants of QoL for this population. A total of 56 studies were extracted from literature searches of relevant databases for empirical reports published between 1966 and 2005 examining the relationship between positive, negative, and/or general psychiatric symptoms and QoL. Weighted effect size analyses revealed small relationships between psychiatric symptoms and QoL, with general psychopathology showing the strongest negative associations across all QoL indicators. Moderator analyses indicated that variation in effect sizes could be accounted for by differing operationalizations of QoL, study design, sample, and participant treatment setting. In particular, positive and negative symptoms were more strongly related to poor QoL among studies of schizophrenia outpatients, whereas general psychopathology showed a consistent negative relationship with QoL across all study samples and treatment settings. Implications for future research and treatment development are discussed.

Humans↗

Design of an in-water corrector system.

The optical design of systems for use in water is considered. Use of flat and concentric dome ports are discussed as well as problems with pupil location that are due to the dome-water interface. Data for the optical properties of seawater and various port materials are presented as well as a sample design.

Journal Article↗

Direct detection and identification of Mycobacterium tuberculosis in smear-positive sputum samples by fluorescence in situ hybridization (FISH) using peptide nucleic acid (PNA) probes.

SETTING: Peptidenucleic acid (PNA) probesdesigned for specific detection of mycobacteria of the Mycobacterium tuberculosis complex (MTC) and other non-tuberculous mycobacterium species (NTM) are shown to be able to penetrate the mycobacterial cell wall and subsequently hybridize in situ to complementary rRNA. OBJECTIVE: To demonstrate the use of fluorescein-labelled PNA probes for detection and identification of M. tuberculosis in smear-positive sputum samples. DESIGN: The sensitivity and specificity of the PNA probes were investigated by fluorescence in situ hybridization (FISH) using cultures of mycobacterium strains representing species of the MTC and NTM, respectively. RESULTS: M. tuberculosis strains were detected by FISH using specific fluorescein-labelled PNA probes directly in smear-positive sputum samples without changing the morphology of the cells. CONCLUSION: PNA probes allow for rapid diagnosis of tuberculosis in smear-positive cases.

Humans↗

Assessment of relationships between site-specific variables.

The assessment of relationships between site-specific variables has been a matter of controversy because of the claim that periodontal sites within individuals can be used as independent observations in statistical models. One problem with this approach is the unreliability of the calculated Type I and Type II error rates. Another problem is that such inappropriate analysis may prohibit a correct assessment of causal relationships between site-specific variables. The host-factor can act as an effect modifier and modulate the magnitude of the site-specific effects and/or the host-factor can act as a confounder by superimposing a patient-effect on the studied site-specific effects leading to bias. As a result, site-specific biological mechanisms of disease progression may be misinterpreted. Sites can be used as the experimental unit of analysis, but the sampling design from which the site-specific data originated should not be ignored.

Causality↗

Complementary and alternative medicine use among midlife women for reasons including menopause in the United States: 2002.

OBJECTIVE: The use of complementary and alternative medicine (CAM) has been examined previously for midlife women only in regional studies. The purpose of this study was to obtain national estimates of CAM use. DESIGN: Data were obtained from the 2002 National Health Interview Survey, which included a CAM supplementary questionnaire. The response rate was 74%. The analysis included 3,621 female respondents between 45 and 57 years of age who had answered all of the relevant questions. SUDAAN software was used to account for the complex sampling design. RESULTS: Forty-five percent of women 45 to 57 years of age had used some form of CAM within the last 12 months. Approximately 25% used biologics (e.g., herbs) or mind-body (e.g., biofeedback) modalities, whereas only 15% used body work (massage and chiropractic medicine). Use did not vary by age, but white race, higher education, and residence in the West were associated with increased use. Only 45% of CAM users mentioned its use to a medical provider. The most cited reason for using CAM involved treatment of pain, with only 3% mentioning menopause. However, the odds for use of CAM were almost twice as high for women with menopausal symptoms in the past year compared with women with no symptoms (odds ratio: 1.9, 95% CI: 1.6-2.2). CONCLUSIONS: CAM use among midlife U.S. women is high, although CAM is not used specifically for menopausal concerns. These data will be useful as a benchmark of the use of CAM as use of conventional menopause therapies are influenced by the Women's Health Initiative results.

Complementary Therapies↗

Psychological and behavioral treatment of insomnia:update of the recent evidence (1998-2004).

BACKGROUND: Recognition that psychological and behavioral factors play an important role in insomnia has led to increased interest in therapies targeting these factors. A review paper published in 1999 summarized the evidence regarding the efficacy of psychological and behavioral treatments for persistent insomnia. The present review provides an update of the evidence published since the original paper. As with the original paper, this review was conducted by a task force commissioned by the American Academy of Sleep Medicine in order to update its practice parameters on psychological and behavioral therapies for insomnia. METHODS: A systematic review was conducted on 37 treatment studies (N = 2246 subjects/patients) published between 1998 and 2004 inclusively and identified through Psyclnfo and Medline searches. Each study was systematically reviewed with a standard coding sheet and the following information was extracted: Study design, sample (number of participants, age, gender), diagnosis, type of treatments and controls, primary and secondary outcome measures, and main findings. Criteria for inclusion of a study were as follows: (a) the main sleep diagnosis was insomnia (primary or comorbid), (b) at least 1 treatment condition was psychological or behavioral in content, (c) the study design was a randomized controlled trial, a nonrandomized group design, a clinical case series or a single subject experimental design with a minimum of 10 subjects, and (d) the study included at least 1 of the following as dependent variables: sleep onset latency, number and/or duration of awakenings, total sleep time, sleep efficiency, or sleep quality. RESULTS: Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders. Nine studies documented the benefits of insomnia treatment in older adults or for facilitating discontinuation of medication among chronic hypnotic users. Sleep improvements achieved with treatment were well sustained over time; however, with the exception of reduced psychological symptoms/ distress, there was limited evidence that improved sleep led to clinically meaningful changes in other indices of morbidity (e.g., daytime fatigue). Five treatments met criteria for empirically-supported psychological treatments for insomnia: Stimulus control therapy, relaxation, paradoxical intention, sleep restriction, and cognitive-behavior therapy. DISCUSSION: These updated findings provide additional evidence in support of the original review's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia. Nonetheless, further research is needed to develop therapies that would optimize outcomes and reduce morbidity, as would studies of treatment mechanisms, mediators, and moderators of outcomes. Effectiveness studies are also needed to validate those therapies when implemented in clinical settings (primary care), by non-sleep specialists. There is also a need to disseminate more effectively the available evidence in support of psychological and behavioral interventions to health-care practitioners working on the front line.

Adult↗

Factors associated with the likelihood of Giardia spp. and Cryptosporidium spp. in soil from dairy farms.

A study was conducted to identify factors associated with the likelihood of detecting Giardia spp. and Cryptosporidium spp. in the soil of dairy farms in a watershed area. A total of 37 farms were visited, and 782 soil samples were collected from targeted areas on these farms. The samples were analyzed for the presence of Cryptosporidium spp. oocysts, Giardia spp. cysts, percent moisture content, and pH. Logistic regression analysis was used to identify risk factors associated with the likelihood of the presence of these organisms. The use of the land at the sampling site was associated with the likelihood of environmental contamination with Cryptosporidium spp. Barn cleaner equipment area and agricultural fields were associated with increased likelihood of environmental contamination with Cryptosporidium spp. The risk of environmental contamination decreased with the pH of the soil and with the score of the potential likelihood of Cryptosporidium spp. The size of the sampling site, as determined by the sampling design, in square feet, was associated nonlinearly with the risk of detecting Cryptosporidium spp. The likelihood of the Giardia cyst in the soil increased with the prevalence of Giardia spp. in animals (i.e., 18 to 39%). As the size of the farm increased, there was decreased risk of Giardia spp. in the soil, and sampling sites which were covered with brush or bare soil showed a decrease in likelihood of detecting Giardia spp. when compared to land which had managed grass. The number of cattle on the farm less than 6 mo of age was negatively associated with the risk of detecting Giardia spp. in the soil, and the percent moisture content was positively associated with the risk of detecting Giardia spp. Our study showed that these two protozoan exist in dairy farm soil at different rates, and this risk could be modified by manipulating the pH of the soil.

Agriculture↗

Children facing a family member's acute illness: a review of intervention studies.

BACKGROUND: A review of psycho-educational intervention studies to benefit children adapting to a close (parent, sibling, or grandparent) family member's serious illness was conducted. OBJECTIVES: To review the literature on studies addressing this topic, critique research methods, describe clinical outcomes, and make recommendations for future research efforts. DATA SOURCES: Research citations from 1990 to 2005 from Medline, CINAHL, Health Source: Nursing/Academic Edition, PsycARTICLES, and PsycINFO databases were identified. REVIEW METHODS: Citations were reviewed and evaluated for sample, design, theoretical framework, intervention, threats to validity, and outcomes. Reviewed studies were limited to those that included statistical analysis to evaluate interventions and outcomes. RESULTS: Six studies were reviewed. Positive outcomes were reported for all of the interventional strategies used in the studies. Reviewed studies generally lacked a theoretical framework and a control group, were generally composed of small convenience samples, and primarily used non-tested investigator instruments. They were diverse in terms of intervention length and intensity, and measured short-term outcomes related to participant program satisfaction, rather than participant cognitive and behavioral change. CONCLUSIONS: The paucity of interventional studies and lack of systematic empirical precision to evaluate intervention effectiveness necessitates future studies that are methodologically rigorous.

Acute Disease↗

Surveillance for selected maternal behaviors and experiences before, during, and after pregnancy. Pregnancy Risk Assessment Monitoring System (PRAMS), 2000.

PROBLEM/CONDITION: Various maternal behaviors and experiences are associated with adverse health outcomes for both the mother and the infant. These behaviors and experiences can occur before pregnancy (e.g., insufficient intake of folic acid), during pregnancy (e.g., complications requiring hospitalization, such as high blood pressure), and after pregnancy (e.g., inadequate follow-up of infants who were discharged early). Information regarding maternal behaviors and experiences is needed to monitor trends, to enhance the understanding of the relations between behaviors and health outcomes, to plan and evaluate programs, to direct policy decisions, and to monitor progress toward Healthy People 2010 objectives (US Department of Health and Human Services. Healthy People 2010. 2nd. ed. With understanding and improving health and objectives for improving health [2 vols.]. Washington DC: US Department of Health and Human Services, 2000). REPORTING PERIOD COVERED: This report covers data for 2000. DESCRIPTION OF SYSTEM: The Pregnancy Risk Assessment Monitoring System (PRAMS) is an ongoing, state- and population-based surveillance system designed to monitor selected self-reported maternal behaviors and experiences that occur before, during, and after pregnancy among women who deliver a live-born infant in 31 states and New York City. PRAMS employs a mixed-mode data collection methodology; as many as three self-administered surveys are mailed to a sample of mothers, and nonresponders are followed up with a telephone interview. Self-reported survey data are linked to selected birth certificate data and weighted for sample design, nonresponse, and noncoverage to create annual PRAMS analysis data sets. PRAMS data can be used to produce statewide estimates of various perinatal health behaviors and experiences among women delivering a live infant. Four indicators for the year 2000 (multivitamin use, pregnancy-related complications, infant checkup, and postpartum contraceptive use) from 19 states are examined in this report. RESULTS: In 2000, the prevalence of multivitamin use > or =4 times per week in the month before pregnancy ranged from 25.0% to 40.7% across the 19 states. Prevalence of pregnancy-related complications requiring hospitalization ranged from 8.8% to 16.3%. Prevalence of infant checkups within 1 week of early (< or =48 hours) hospital discharge ranged from 51.5% to 88.6%. Prevalence of postpartum contraceptive use ranged from 77.9% to 89.9%. INTERPRETATION: PRAMS data indicate that 19 states are well below the Healthy People 2010 objective for folic acid consumption, as measured by multivitamin use. Data for infant checkups indicate that guidelines for care are not being followed for as many as half of those discharged early. However, data for additional years are needed to assess trends in these four indicators. PUBLIC HEALTH ACTION: State maternal and child health programs can use these population-based data to monitor progress toward Healthy People 2010 objectives, evaluate adherence to guidelines for care, and assess changes in prevalence of other health behaviors. The data can be shared with policy makers to direct policy decisions that might affect the health of mothers and infants. By providing data on maternal behaviors and experiences that are associated with adverse outcomes, PRAMS supports the activities of two CDC initiatives-to promote safe motherhood and to reduce infant mortality and low birthweight.

Contraception Behavior↗

[Requests for microbiological diagnosis by primary care physicians in the Salamanca area].

OBJECTIVES: To assess requests for microbiological analysis made by Primary Care doctors and to evaluate the quality of the procedure by the indicator: proportion of contaminated urine samples. DESIGN: A retrospective crossover study of requests to the Microbiology Laboratory in the University Hospital of Salamanca during 1995. SETTING: The study covered the Salamanca Health Area, which consists of 35 Health Centres and a catchment population of 358,408. PATIENTS AND OTHER PARTICIPANTS: The requests for microbiological diagnosis and results of the 43,317 samples processed were analysed. INTERVENTIONS: The data was distributed according to care level and the Area's Health Centres. MEASUREMENTS AND RESULTS: 9,574 (22%) of the total number of samples received turned out positive, 27.4% of the requests originated in Primary Care (PC). The overall request rate from PC was 33 per 1,000 inhabitants. CONCLUSIONS: The microbiological analysis most frequently requested from PC is urine culture. Relationship between request and positives is 4 to 1.

Bacteria↗

Interpretation and estimation of summary ratios under heterogeneity.

Of the several types of summary odds ratios in use in epidemiology, only those proposed by Mantel and Haenszel and Miettinen do not assume homogeneity (constancy) of stratum-specific parameters. Under heterogeneity, Miettinen's estimators consistently estimate meaningful epidemiologic parameters, whereas the asymptotic expectation of the Mantel-Haenszel odds ratio varies according to irrelevant features of the sampling design. Although one can modify the Mantel-Haenszel summary to overcome the latter problem, one can also extend the Miettinen estimators to sparse data and thus limit the use of Mantel-Haenszel summaries to situations in which the homogeneity hypothesis is reasonable. This paper provides formulae for the extended Miettinen estimators and large-sample variances and confidence limits for summary ratios under heterogeneity.

Epidemiologic Methods↗

Influence of sampling site on concentrations and carbohydrate-degrading enzyme activities of protozoa and bacteria in the rumen.

Four ruminally cannulated cows were used to assess the distribution of the concentrations and carbohydrate-degrading enzyme activities of the liquid-associated protozoa (LAP) and solid-associated bacteria (SAB) in the rumen. The cows were fed diets (7 kg of DM/d) of 100% hay (Diet F) or 60% barley plus 40% hay (Diet C) in a 2 x 2 crossover experimental design. Samples of ruminal digesta were collected successively from the dorsal (DS), ventral (VS), and anterior (AS) sacs 1h before and 3 h after the morning feeding on two sampling days with a 2-d interval. Irrespective of diet and sampling time, the greatest proportion of entodiniomorphs, representing the main population of protozoa, was found in the DS (40% mean; P < .05). Low pH values observed in the DS (P < .05) indicated higher fermentative activity in this site than in the other parts of the rumen. Protozoa may contribute more than previously thought to the high digestive potential present at the top of the rumen that has classically been attributed to bacteria. The specific activity of plant cell wall polysaccharide-degrading enzymes in the LAP was correspondingly greater (P < .05) for DS than for VS or AS. For the two diets and sampling times, specific activity of fibrolytic enzymes in the SAB tended to be less in the upper than in the lower parts of the rumen, and less in the VS than in the AS. This tendency became significant (P < .05) for total fibrolytic enzyme activity. Differences in bacterial colonization of particles among the three sampling sites may explain such differences in fibrolytic activity of the SAB. Data suggest a spatio-temporal complementary action of the bacteria and protozoa in ruminal plant cell wall degradation, at least with the barley diet, for which the number of protozoa was highest.

Animals↗

The effect of regulation caused by a dam on the distribution of the functional feeding groups of the benthos in the sub basin of the Grande River (san Luis, Argentina).

The construction of small dams in principal streams is one of the most common forms of regulation in the province of San Luis since they cause changes of physical, chemical and biological nature downstream. The purpose of this study was to analyze the short-term modifications in the food organization of benthic macroinvertebrates communities due to the construction of a dam in the Grande River (San Luis, Argentina). Two sampling sites were established: one before the dam and another one after it. The samplings were carried out with Surber sampler and during an annual cycle extending from April 1997 to March 1998, and two complementary samplings were done in low and high waters. The field sampling design was stratified randomly, and 3 pseudo replicas were taken in a transect seasonally and monthly and were then averaged. Macroinvertebrates were classified in different functional feeding groups. The comparisons at the level of physical and chemical variables and absolute abundances of the functional groups were carried out by means of the Wilcoxon test for two related samples. The collector-filterers, scrapers and predators increase whereas the collector-gatherers and shredders decreased. There were significant differences at the level of gatherers and shredders.

Animals↗

Psycho-educational strategies to promote fluid adherence in adult hemodialysis patients: a review of intervention studies.

BACKGROUND: We reviewed psycho-educational intervention studies that were designed to reduce interdialytic weight gain (IDWG) in adult hemodialysis patients. Our goals were to critique research methods, describe the effectiveness of tested interventions, and make recommendations for future research. METHODS: Medline, PsychInfo, and the Cumulative Index to Nursing and Applied Health (CINAHL) databases were searched to identify empirical work. Each study was evaluated in terms of sample, design, theoretical framework, intervention delivery, and outcome. RESULTS: Nine studies were reviewed. Self-monitoring appears to be a promising strategy to be considered to reduce IDWG. Theory was not usually used to guide interventions, designs generally had control groups, interventions were delivered individually, more than one intervention was delivered at a time, the duration of the intervention varied greatly, there was no long-term follow-up, IDWG was the only outcome, and IDWG was operationalized in different ways. CONCLUSIONS: Theoretical models and methodological rigor are needed to guide future research. Specific recommendations on design, measurement, and conceptual issues are offered to enhance the effectiveness of future research.

Adult↗

Age-specific incidence of Alzheimer's disease in a community population.

OBJECTIVE: To determine age-specific incidence rates of clinically diagnosed Alzheimer's disease. DESIGN: Cohort, followed a mean of 4.3 years. SETTING: East Boston, Mass. PARTICIPANTS: Of 2313 persons aged 65 years and older who were initially free of Alzheimer's disease, 1601 participated in the ascertainment of incident disease (80% of survivors), 409 declined participation, and 303 died before the end of the follow-up period. A stratified sample of 642 persons received detailed clinical evaluation. OUTCOME MEASURE: Diagnosis of new probable Alzheimer's disease through structured clinical evaluation including neurologic, neuropsychological, and psychiatric examination. Community incidence rates were computed by 5-year age groups, adjusted for gender, single year of age, length of follow-up interval, and sampling design. RESULTS: The estimated annual incidence of Alzheimer's disease in the population was 0.6% (95% confidence interval [CI], 0.3% to 0.9%) for persons aged 65 to 69 years, 1.0% (95% CI, 0.6% to 1.4%) for persons aged 70 to 74 years, 2.0% (95% CI, 1.3% to 2.7%) for persons aged 75 to 79 years, 3.3% (95% CI, 2.2% to 4.4%) for persons aged 80 to 84 years, and 8.4% (95% CI, 3.7% to 13.1%) for persons aged 85 years and older. CONCLUSIONS: The incidence of Alzheimer's disease is substantial and is approximately 14 times higher among persons older than 85 years compared with those between 65 and 69 years of age.

Age Distribution↗

Attitudes toward blood donation incentives in the United States: implications for donor recruitment.

BACKGROUND: The potential effectiveness of various donation incentive programs may vary by demographics, first-time or repeat status, and collection site. STUDY DESIGN AND METHODS: Attitudes toward future incentives were obtained from a 1998 anonymous survey sent to 92,581 US blood donors. Responses (encouraged, discouraged, no difference) to incentives were compared within demographic groups, donations sites, and between first-time and repeat community whole-blood (WB) donors using chi-square tests and logistic regressions adjusted for sample design. RESULTS: Incentives most likely to encourage donation return among all 45,588 WB respondents were blood credits (61%), cholesterol screening (61%), and prostate-specific antigen (PSA) screening (73% of men). Younger donors (< or = 25 years old) were 4 to 5 times more likely to be encouraged to donate if offered compensatory incentives (tickets to events, discounts or lottery and/or raffle tickets), gifts, or a token of appreciation than were those donors older than 55. This age effect influenced positive attitudes toward incentives in first-time donors and in donors giving at schools, universities, or military sites. Among all donors, up to 7 to 9 percent reported they would be discouraged to return if offered compensatory incentives. CONCLUSIONS: Blood credits and cholesterol and PSA screening would be well received at all donation sites. Gifts, compensatory incentives, and tokens of appreciation appeal more to younger donors. These data may allow blood centers to optimize recruitment by tailoring limited incentive resources more effectively.

Adult↗