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[Development of a city planning hygiene analysis and its application in the framework of an environmental-epidemiological study].

A "town-planning hygienic analysis" is presented which has been developed within an environmental epidemiological study. This analysis contains 7 marks (maximum sound pressure level Lmax, equivalent pressure level Leq, housing conditions/sanitary, size of flat, brightness/day-light ratio, environment, building order) whose quality is scored into 3 categories (very good/good, sufficient, insufficient). The evaluation is performed by relating the frequency of the proportional quality as well as the score for the general quality, which is constructed by the mean of the proportional qualities. First results are discussed with a comparative study on 297 flats.

City Planning↗

'Truthsets' for clinical validation of large-scale functional assays: Practice recommendations from Cancer Variant Interpretation Group UK (CanVIG-UK).

BACKGROUND: Large-scale functional assays, including multiplex assays of variant effect, have substantial potential to resolve variants of uncertain significance (VUS), particularly for rare missense variants where clinical and population evidence are limited. The ClinGen assay-level clinical validation framework described by Brnich et al provided baseline guidance for the use of functional data for variant classification. However, clear consensus regarding construction of variant 'truthsets' by which to clinically validate functional data remains lacking. METHODS: CanVIG-UK developed consensus recommendations for truthset construction through an iterative national consultation process involving the CanVIG Steering Advisory Group (CStAG), wider CanVIG-UK membership, and engagement with international functional genomics experts. Consultation was based on previous analyses of 2,120 truthset constructions examining the impact of truthset composition on evidence point allocation within the ClinGen assay-level clinical validation framework. RESULTS: Across several consultations, CanVIG-UK established nine guiding principles and seven best-practice recommendations for assay-level clinical validation, using the assumed context of an assay for a cancer susceptibility gene where loss-of-function is the mechanism of pathogenicity. The principal recommendation stipulates, where assays are intended for use in interpretation of largely missense variants, the truthset used to validate should comprise only missense variants. Rather than mixtures of different variant types which may serve to over-estimate assay performance. Additional recommendations support option for relaxation of truthset stringency to improve power, augmentation of benign missense truthsets with systematically derived 'proxy-clinical' benign variants, independent clinical validation separate from assayist-defined validation, and careful evaluation of missense score distributions against that of protein-truncating and synonymous variants. Guidance is also provided for scenarios with limited pathogenic truthset availability and for assays reporting multiple deleterious zones or readouts. CONCLUSIONS: The CanVIG-UK principles and recommendations for truthset construction upon the ClinGen assay-level clinical validation framework, while aiming to form a baseline for future discussion regarding other functional and disease contexts and helping to address the gap between publication of new data and routine clinical implementation.

Journal Article↗

Holmium laser enucleation of the prostate for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

RATIONALE: A range of surgical options is available for the treatment of benign prostatic hyperplasia (BPH), including holmium laser enucleation of the prostate (HoLEP). The evidence is unclear regarding differences in functional, perioperative, and morbidity outcomes between these modalities. OBJECTIVES: To assess the effects of holmium laser enucleation of the prostate compared with other surgical treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We searched multiple databases (including MEDLINE, Embase, CENTRAL, Web of Science, LILACS, and the International HTA database), trial registries, and conference abstracts through April 08, 2026. ELIGIBILITY CRITERIA: We only included randomized trials of men over 40 years of age with a prostate volume of at least 20 mL (assessed by digital rectal examination, ultrasound, or conventional imaging) who exhibited lower urinary tract symptoms (LUTS) defined by an International Prostate Symptom Score (IPSS) of eight or greater undergoing surgical interventions for BPH. OUTCOMES: The critical outcomes measured were the urologic symptoms score, the quality-of-life score, and major adverse events. The important outcomes measured were: re-treatment, erectile function, ejaculatory function, transfusions, acute urinary retention, indwelling urinary catheter duration, and hospital stay duration. RISK OF BIAS: We used the Cochrane risk of bias tool (RoB 1) to assess for potential sources of bias on a study and outcome level basis. SYNTHESIS METHODS: We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed statistical heterogeneity in the pooled data by visually inspecting forest plots and using the I2 statistic to quantify it. We used the GRADE framework to assess the certainty of evidence. INCLUDED STUDIES: We included 52 trials that included 6242 participants that compared HoLEP to other surgical interventions for benign prostatic hyperplasia. The median age of participants across the studies ranged from 65 to 74 years. The baseline prostate volume ranged from 30 cc to 142 cc. Baseline IPSS scores ranged from 19.6 to 28.6 (range 0-35). SYNTHESIS OF RESULTS: We prioritized comparing HoLEP with transurethral resection of the prostate (TURP) at short-term follow-up (up to 12 months), because TURP is the long-standing reference standard and the predominant comparator in randomized surgical trials. Findings for the four remaining comparisons (laser ablation, alternative energy source enucleation, other minimally invasive therapies, and simple prostatectomy), for long-term follow-up, and for all remaining outcomes are reported in full in the review. Compared to TURP, at short-term follow-up: Critical outcomes - HoLEP may result in little to no difference in short-term urologic symptom scores measured using the IPSS (range 0 to 35; lower values reflect fewer symptoms) (MD -0.67, 95% CI -1.20 to -0.14; I² = 93%; 14 studies, 1666 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term quality of life (range 0 to 6; lower values reflect better quality of life) (MD -0.04, 95% CI -0.23 to 0.15; I² = 73%; 6 studies, 876 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term major adverse events (RR 0.75, 95% CI 0.35 to 1.58; I² = 0%; 10 studies, 1147 participants, low-certainty evidence). Important outcomes - HoLEP likely results in little to no difference in re-treatment (RR 0.45, 95% CI 0.14 to 1.50; I² = 0%; 8 studies, 813 participants, moderate-certainty evidence). - HoLEP likely results in little to no difference in erectile function (MD -0.03, 95% CI -0.47 to 0.42; I² = 0%; 3 studies, 518 participants, moderate-certainty evidence). - Ejaculatory function: we did not find any data for this outcome. - HoLEP likely reduces the need for blood transfusion (RR 0.19, 95% CI 0.09 to 0.42; I² = 0%; 15 studies, 1755 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with TURP, HoLEP may achieve similar relief of urologic symptoms, similar quality of life, and similar rates of major adverse events in the first 12 months after surgery, and probably similar re-treatment rates and erectile function. HoLEP likely reduces the need for blood transfusion; this is the only advantage of HoLEP that the randomized evidence, as summarized here, supports as clinically important. There was insufficient evidence to assess outcomes in the subset of individuals with larger prostates or on anticoagulation. Future research should prioritize long-term trials reporting sexual function and urinary incontinence outcomes, recruit men with very large prostates (≥ 150 cc) or on anticoagulation therapy, and evaluate cost-effectiveness and training requirements. FUNDING: No external funding was received for this review. REGISTRATION: The protocol for this review was published in the Cochrane Database 2019 (https://doi.org/10.1002/14651858.CD013291).

Humans↗

Machine learning-based prediction of unplanned readmission and construction of an online calculator for elderly patients with mild ischemic stroke.

OBJECTIVE: To screen for independent risk factors for unplanned readmission in elderly patients with mild ischemic stroke, and to construct and validate an online risk prediction calculator based on an interpretable machine learning model, thereby providing a promising practical tool for accurate clinical assessment of 30&#x2011;day all&#x2011;cause unplanned readmission risk in this population. METHODS: A prospective cohort study was conducted, including 1050 patients aged&#xa0;&#x2265;&#xa0;60&#xa0;years with mild ischemic stroke admitted between August 2023 and September 2024. Participants were randomly divided into a training set (840 cases) and a test set (210 cases) at a ratio of 8:2. Risk factors were screened by univariate analysis and multivariable Logistic regression. Four machine learning models, namely LightGBM, XGBoost, Random Forest, and K&#x2011;Nearest Neighbors (KNN), were developed and their performance was evaluated using AUC, accuracy, sensitivity, and specificity as metrics. The SHAP framework was used for interpretability analysis, and an online calculator was subsequently developed based on the optimal model. RESULTS: Univariate analysis showed significant differences (P&#xa0;<&#xa0;0.05) in 13 factors including age, smoking, AIP, TyG index, HALP score, etc. Multivariable Logistic regression identified age (OR&#xa0;=&#xa0;9.752), smoking (OR&#xa0;=&#xa0;5.171), AIP (OR&#xa0;=&#xa0;6.691), TyG index (OR&#xa0;=&#xa0;4.393), HALP score (OR&#xa0;=&#xa0;2.831), and&#xa0;&#x2265;&#xa0;2 comorbidities (OR&#xa0;=&#xa0;3.664) as independent risk factors. All four machine learning models demonstrated good predictive performance. Based on a comprehensive evaluation of multiple metrics and computational efficiency, the LightGBM model exhibited the best predictive performance (AUC&#xa0;=&#xa0;0.884, accuracy&#xa0;=&#xa0;0.829, sensitivity&#xa0;=&#xa0;0.812, specificity&#xa0;=&#xa0;0.875). SHAP analysis showed that age, AIP, TyG index, smoking, and HALP score were key predictors. An online calculator developed based on this model enables individualized risk predictions. CONCLUSION: Key risk factors associated with 30&#x2011;day unplanned readmission in elderly patients with mild ischemic stroke were identified. The LightGBM model demonstrated high predictive accuracy, and together with the interpretability analysis and online calculator, offers a practical tool to support clinical risk assessment. However, this tool requires future external validation.

Humans↗

A longitudinal assessment of the aquatic macroinvertebrate community in the channelized lower Missouri River.

We conducted an aquatic macroinvertebrate assessment in the channelized reach of the lower Missouri River, and used statistical analysis of individual metrics and multimetric scores to identify community response patterns and evaluate relative biological condition. We examined longitudinal site differences that are potentially associated with water quality related factors originating from the Kansas City metropolitan area, using data from coarse rock substrate in flowing water habitats (outside river bends), and depositional mud substrate in slack water habitats (dike fields). Three sites above river mile (RM) 369 in Kansas City (Nebraska City, RM = 560; St. Joseph, RM = 530; Parkville, RM = 377) and three below (Lexington, RM = 319; Glasgow, RM = 228; Hermann, RM = 94) were sampled with rock basket artificial substrates, a qualitative kicknet method, and the Petite Ponar. We also compared the performance of the methods used. A total of 132 aquatic macroinvertebrate taxa were collected from the lower Missouri River; one third of these taxa belonged to the sensitive EPOT insect orders (Ephemeroptera, Plecoptera, Odonata, and Trichoptera). Rock baskets had the highest mean efficiency (34.1%) of the methods, and the largest number of taxa was collected by Ponar (n = 69) and kicknet (n = 69) methods. Seven of the 15 metrics calculated from rock basket data, and five of the nine metrics calculated from Ponar data showed highly significant differences (ANOVA, P < 0.001) at one or more sites below Kansas City. We observed a substantial reduction in net-spinning Trichoptera in rock habitats below Kansas City (Lexington), an increase in relative dominance of Oligochaeta in depositional habitats at the next site downstream (Glasgow), and lower relative condition scores in rock habitat at Lexington and depositional habitat at Glasgow. Collectively, these data indicate that some urban-related impacts on the aquatic macroinvertebrate community are occurring. Our results suggest that the methods and assessment framework we used in this study could be successfully applied on a larger scale with concurrent water and sediment chemistry to validate metrics, establish impairment levels, and develop a specific macroinvertebrate community index for the lower Missouri River. We recommend accomplishing this with longitudinal multi-habitat sampling at a larger number of sites related to all potential sources of impairment, including major tributaries, urban areas, and point sources.

Animals↗

[Reduced serotonin levels in platelet-free plasma of adolescents with externalizing behaviour problems].

OBJECTIVES: A serotonergic dysfunction, in particular a reduced serotonergic neurotransmission in the frontal cortex and limbic brain regions, has been discussed in connection with the aetiology of aggressive and impulsive behaviour. Assessment of the activity in the central serotonergic system in children and adolescents is limited due to its technical complexity and ethical restrictions. Therefore, peripheral serotonergic parameters have been used as a model to obtain deeper insight into central serotonergic functions. The aim of this investigation is to examine the significance of plasma serotonin measurement with regard to behavioural problems in adolescents at risk for psychopathology. METHODS: Within the framework of a prospective longitudinal study of children at risk, serotonin levels in platelet-free blood plasma were measured in a group of n = 10 adolescents aged 15 years with persistent externalizing behaviour (T-score > or = 60 on the "Externalizing Problems" scale of the CBCL) and in a control group of n = 20 mentally undisturbed adolescents. Groups were matched according to age and gender. Externalizing behaviour was assessed by means of a parent questionnaire, the Achenbach Child Behavior Checklist (CBCL). RESULTS: Significantly lower levels of plasma serotonin were found in adolescents with persistent behaviour problems than in the control group. Significant negative correlations between serotonin levels and the CBCL scales "Aggressive Behavior" and "Externalizing Problems" were obtained for the total sample. CONCLUSIONS: Earlier findings that described a serotonergic deficit as a key mechanism in the manifestation of aggressive and antisocial behaviour are confirmed for adolescents at risk taken from a community sample.

Adolescent↗

Coping with crises: an examination of the impact of traumatic events on religious beliefs.

The impact of traumatic events on empirical and metaphysical assumptions was examined, by comparing assumptions of a group of 25 persons who had recently experienced a major stressor with assumptions of a group of 25 persons who had not had such an experience. Each group was composed of 22 women and 3 men, with a mean age of 20 years. Participants completed written measures assessing levels of adjustment, empirical world assumptions, religious motivation, and religious and spiritual experiences. Naturalistic interviews were conducted with the trauma group. The trauma group obtained significantly higher scores on symptoms of psychological distress but did not differ in evaluations of the empirical world as predictable, safe, or controllable. Interviews suggested that the metaphysical assumptions were not challenged by trauma; rather, they provided a framework for understanding and coping with trauma.

Adaptation, Psychological↗

Health-promoting behaviors of sheltered homeless women.

To expand the body of knowledge and provide further insight into the complex area of homelessness and health, health practices of sheltered homeless women were investigated using a cross-sectional, descriptive, and non-experimental design using Pender's Health Promotion Model as the theoretical framework. The sample (n=137) was well educated, mostly unemployed, primarily single, and homeless due to relationship problems/conflict per self-report. Homeless women were noted to practice health-promoting behaviors in all areas but scored the lowest on physical activity and nutrition. Significant findings reflected women's personal strengths and resources in the areas of spiritual growth and interpersonal relations.

Adolescent↗

The children's self-report questionnaire: factor score age trends and gender differences.

Age trends and gender differences in a normative sample of 1,676 children (6- to 13-years) were explored with the use of scores obtained from the Children's Self-Report Questionnaire (SRQ). Several interesting trends emerged. Boys scored higher than girls on Conduct Problems, and girls scored higher than boys on dimensions labeled Worry and Sensitive-Emotional. Scores on other SRQ factors exhibited orderly increases or decreases across age groups. These trends are discussed in an attempt to clarify behavioral cognitive and affective age appropriate norms and are cautiously interpreted within a developmental framework. The identification of age and gender trends are a necessary step in the development of a diagnostic instrument intended for use with children. The age and gender trends observed lend additional support to the validity of the SRQ.

Affective Symptoms↗

Predictors of breast self-examination practice among elderly women.

The purpose of the study presented in this article was to examine predictors of breast self-examination (BSE) practice among elderly female subjects in selected senior citizen centers. The health belief model served as the theoretical framework for the research study. Both the frequency of BSE performance and the technique subjects used to examine their breasts were measured by a questionnaire. Subjects who perceived few barriers to BSE had higher BSE technique scores. The findings also indicated that receiving instruction through a class on BSE was related to improved BSE technique. Perceived susceptibility to breast cancer and perceived benefits of BSE were not found to be significantly predictive of BSE practice.

Aged↗

Hostility and perceived social support: interactive effects on cardiovascular reactivity to laboratory stressors.

BACKGROUND: Previous research has identified trait hostility and social isolation as possible psychosocial risk factors for coronary heart disease (CHD). However, few studies have examined hostility and social support simultaneously to determine their independent and possible interactive relations with CHD and disease-promoting mechanisms. PURPOSE: Hypotheses derived from a general interpersonal model were tested in a study examining trait hostility and perceived social support as predictors of cardiovascular reactivity to laboratory stressors. METHODS: Healthy college students (53 men, 55 women) performed speech and mental arithmetic tasks while blood pressure and heart rate were monitored. RESULTS: There was an interactive effect of hostility and perceived social support on systolic and diastolic blood pressure (SBP and DBP) reactivity. Higher hostility scores were associated with greater SBP reactivity for participants who were high in perceived social support; whereas for those with low social support scores, greater hostility was associated with somewhat less SBP reactivity. The same pattern was obtained for DBP, but only during the speech task. CONCLUSIONS: These findings encourage further research conceptualizing trait hostility within a general interpersonal framework that calls attention to both positive and negative person-environment transactions.

Adult↗

Evidence assessment of management of acute otitis media: II. Research gaps and priorities for future research.

OBJECTIVES: To report research gaps and priorities of future research identified during an evidence assessment process on the management of acute otitis media (AOM). METHODS: A conceptual framework for management of AOM was developed to guide the evidence assessment. An 11-member technical expert panel guided the selection of key questions, prioritization of influencing factors, development of scope, definition of AOM, and search strategy through polling processes and conference calls. Quality of clinical trials was evaluated using established scales. Outcome measures were abstracted from each study. RESULTS: A total of 3461 titles and abstracts were screened, and 760 full-length articles were reviewed. Of the 760 articles, 80 studies addressed the key questions. In defining AOM, 42 (52.5%) of the 80 studies included the middle-ear effusion component, only 2 (2.5%) included the rapid onset component, and 26 (32.5%) included the signs/symptoms of inflammation component. None of the 80 studies used all 3 components. Of the 74 controlled trials, 39 (53%) were of acceptable quality (Jadad score of 3 or higher). The technical experts did not agree in the ranking of the importance of the 41 influencing factors (Kendall's coefficient of concordance was 0.0022). Another poll also indicated diverse opinions of the experts on the importance of 7 key questions derived from the conceptual framework (Kendall coefficient of concordance is 0.21). Furthermore, our review found that the type and definition of outcome measure varied. CONCLUSIONS: Despite the large body of literature on AOM, its quality is uneven and its findings are not generalizable. Future research should try to answer all key questions and investigate all risk factors in well-designed, scientific studies.

Acute Disease↗

[Transposition of an American-designed comprehensive medical student examination within the framework of the forthcoming French nationwide comprehensive examination. A preliminary study].

Medical training is undergoing extensive revision in France. A nationwide comprehensive clinical competency examination will be administered for the first time in 2004, relying exclusively on essay-questions. Unfortunately, these questions have psychometric shortcomings, particularly their typically low reliability. High score reliability is mandatory in a high-stakes context. The National Board of Medical Examiners-designed multiple choice-questions (MCQ) are well adapted to assess clinical competency with a high reliability score. The purpose of this study was to test the hypothesis that French medical students could take an American-designed and French-adapted comprehensive clinical knowledge examination with this MCQ format. Two hundred and eighty five French students, from four Medical Schools across France, took an examination composed of 200 MCQs under standardized conditions. Their scores were compared with those of American students. This examination was found assess French students' clinical knowledge with a high level of reliability. French students' scores were slightly lower than those of American students, mostly due to a lack of familiarity with this particular item format, and a lower motivational level. Another study is being designed, with a larger group, to address some of the shortcomings of the initial study. If these preliminary results are replicated, the MCQ format might be a more defendable and sensible alternative to the proposed essay questions.

Adult↗

Application of causal discovery of factors driving dissolved oxygen in estuarine environments.

Dissolved oxygen (DO) concentrations in estuarine bottom waters are a manifestation of multiple, interacting physical and biogeochemical processes, yet identifying their independent contributions remains challenging. Here, we analyze monthly water quality monitoring data from eight stations across Long Island Sound from 1994 to 2022 using a causal discovery framework (PCMCI+) and transformation of forcing variables. Our goal is to identify and isolate variables that causally influence bottom DO and improve predictive models by minimizing overfitting and multicollinearity. PCMCI+ reveals surface-layer temperature as the most important and consistent negative driver of bottom DO, followed by stratification. Wind events exhibit only brief relief by advection and mixing, while river discharge shows no direct causal link to DO, making it less influential than previously thought. Biogeochemical variables, including chlorophyll-a (Chl-a), nitrate and nitrite, and particulate carbon, influence DO through both contemporaneous and time-lagged pathways, often with signs that shift depending on the process. The derived models were evaluated by comparing skill scores, mean squared error, and Akaike Information Criterion. Both model types perform well, with coefficient of determination values exceeding 0.90 at multiple stations using only 3-5 predictors. Our analysis reveals that the best causal predictors are surface-layer temperature, stratification, Chl-a, and particle carbon. This approach provides a scalable framework for improving prediction models and understanding the mechanistic links that control the seasonal variability of DO in estuarine systems.

Estuaries↗

Towards an expanded linkage map and exploration on co-dominant scoring of AFLPs in maize.

Simple sequence repeats (SSRs) and amplified fragment length polymorphisms (AFLPs) have become the most important markers for molecular mapping. Primarily based on restriction fragment length polymorphism (RFLP) markers, extensive linkage maps of maize had been developed. To construct a near-saturated genetic linkage map, an expanded maize genetic linkage map was constructed using a population of 234 F2 individuals derived from a cross of X178 and B73 base on an essential SSR framework map of maize. The level of polymorphisms and genetic properties of SSR and AFLP markers were characterized. A total of 249 markers consisting of 130 SSRs and 119 AFLPs have been landed on 10 chromosomes of maize. The 249-locus map spanned 1 659.3 centi-morgans (cM) and had a mean density of 6.66 cM. This mapping population and related information should connect further research involving analysis of quantitative trait loci, comparative genomics, and heterosis. Moreover, in many studies, AFLPs were analyzed on the basis of the presence or absence of a band on the electrophoresis gels. A new method based on double polymorphic bands of co-dominant scoring of AFLPs was explored according to the similarity of loci amplified from AFLP enzyme combination.

Amplified Fragment Length Polymorphism Analysis↗

Acculturation, social alienation, and depressed mood in midlife women from the former Soviet Union.

Level of acculturation has been linked to depressed mood in studies across culturally diverse immigrant groups. The purpose of this study was to determine the effects of acculturation, social alienation, personal and family stress, and demographic characteristics on depressed mood in midlife immigrant women from the former Soviet Union. Structural equation modeling showed that higher acculturation scores, measured by English language and American behavior, were indirectly related to lower scores for depressed mood. Higher acculturation levels promoted mental health indirectly by reducing social alienation and, subsequently, lowering family and personal stress, both of which had direct relationships to symptoms of depression. These findings support the ecological framework that guided our research and point to the importance of focusing on contextual factors in developing interventions for new immigrants.

Acculturation↗

Modeling effects of explicit and nonexplicit sexual stimuli on the sexual anxiety and behavior of women.

This study focused on the specific effects of explicit and nonexplicit sexual stimuli on anxious, coitally inexperienced women. Using Bandura's social learning theory as the thoretical framework, the consequences of modeling behavior on an individual's response patterns were examined. Responses indicating sexual anxiety level, preferred sexual behavior, and manifest anxiety level were recorded. Forty-five women were selected based on their scores on the Short Manifest Anxiety Scale. The subjects were then randomly placed into three treatment groups: explicit, nonexplicit, and control. Analysis of the data revealed significant differences among the women in each of the three groups regarding sexual behavior. Sexual anxiety levels also differed between women in the explicit and control groups. Pre- and posttest manifest anxiety scores also showed a significant difference in the explicit-group women. It has been shown that anxious, coitally inexperienced women who are exposed to sexually explicit stimuli in a controlled situation will have lower sexual anxiety levels, have lowered manifest anxiety levels, and be more willing to participate in a greater variety of sexual behaviors under appropriate circumstances. The results of this study may aid those in the helping professions gain a better understanding of the effects sexual stimuli have on certain individuals.

Adolescent↗

Methodological approaches to the population analysis of toxicity data.

Toxicokinetics is the assessment of systemic exposure in toxicity studies, in which pharmacokinetic data are generated, either as an integral component in the conduct of the nonclinical toxicity studies or in specially designed supportive studies, in order to assess systemic exposure. The data may be used in the interpretation of toxicity findings and contribute to the assessment of the relevance of these findings to clinical safety. Data may be obtained from all animals in a toxicity study, in representative subgroups, in satellite groups or in separate studies. Applying a mixed effects modelling approach in toxicokinetics offers many advantages over the current approach of having satellite groups. Sparse samples for measuring drug/metabolite concentration are collected in all main animals in the majority of studies where toxicological findings are obtained. Such sampling is unlikely to distress the animals, disturb the conduct of a toxicological study or affect the outcome of the study. Many of the outcome measures in toxicological studies are categorical in nature. For example, lesions may be scored on a one to four scale, from none to severe. The analysis of such data is usually carried out using a general mixed modelling approach. We have implemented such models in a nonlinear mixed effects modelling framework which allows us to relate pharmacokinetic response to outcome. A case study is used to illustrate the principles of general mixed effects modelling in toxicokinetics.

Demography↗