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PubMed2026

Predictive evolutionary genomics: principles, validation, and practice.

Climate change and habitat loss are driving rapid evolutionary responses in populations world-wide, which creates an urgent need for evolutionary forecasting in conservation and agriculture. Such forecasting can be categorized into three time scales: trait-based models that use multivariate quantitative genetic equations to project correlated phenotypic responses up to c. 20 generations, allele-based analyses that model allele frequency dynamics up to 100 generations, and composite adaptation scores that aggregate many small effects to yield predictions across longer horizons. However, these approaches have remained largely disconnected. Here, we present a Bayesian framework that integrates these three complementary approaches for evolutionary prediction. Our framework combines genomic, phenotypic, and environmental data to yield probabilistic predictions with explicit uncertainty. We show how predictive evolutionary forecasts can be validated with experimental evolution, field experimentation, historical specimens, and reciprocal transplants. These validated forecasts can help advance conservation and agricultural programmes by helping predict which populations are at risk of future extinction, optimizing breeding programmes for future climates, and planning ecosystem management under environmental change. By supporting a shift towards more predictive approaches in evolutionary biology, this framework may help improve our ability to manage biodiversity and food security in a changing world.

Genomics↗

PubMed1994

Sibling adaptation to childhood cancer collaborative study: prevalence of sibling distress and definition of adaptation levels.

A multisite collaborative study assessed the frequency and intensity of emotional/behavioral distress in siblings of children with cancer. A sample of 254 siblings, aged 4 to 18 years, and their parents completed interviews and self-report measures 6 to 42 (average 22.5) months after diagnosis of cancer in a brother or sister. Matched controls were obtained from respondents to the Child Health Supplement of the National Health Interview Survey administered in 1988 (CHS88). Before diagnosis, the prevalence of parent-reported emotional/behavioral problems among siblings was similar to that in the general population (7.7% vs 6.3%; p = not significant). After diagnosis, prevalence rose to 18% among siblings. When siblings were grouped according to the presence or absence of problems exacerbated by and/or arising after diagnosis, four levels of adaptation, consistent with scores on the Behavior Problem Scales from the CHS88, emerged. This differentiation may help explain inconsistencies in sibling response reported previously and provides a framework for investigating factors that enhance adaptation.

Adaptation, Psychological↗

PubMed1991

[Familiarity, favorability, and cognitive complexity: integration of frequency of interaction hypothesis and vigilance hypothesis].

Previous studies using Bieri's 'cognitive complexity' score had supported 'vigilance hypothesis' which assumed that impressions of unfavorable persons were more complex than favorable persons. Thus, Bieri's measure seemed to be invalid because the findings were completely contrary to 'frequency of interaction hypothesis', presented in the theoretical framework of 'cognitive complexity', which assumed that impressions of familiar persons were more complex than unfamiliar persons, since people could be supposed to have more intimate acquaintance with favorable persons. The purpose of present study was to indicate the invalidity was caused by the research design where familiarity was dependent on favorability and to show that even Bieri's score could support 'interaction hypothesis', if one variables could be statistically orthogonized to the other. In each of two surveys reported, about two hundred female undergraduates completed a Rep test where they rated favorable and unfavorable persons on the basis of some dimensions which included favorability and familiarity. The results obtained through various regression analyses supported the above predictions. Moreover, it was revealed that, with favorability controlled, Bieri's score showed almost linear increases as familiarity increased, though the score of extremely unfamiliar persons was rather higher than the score the linear function could predict.

Adult↗

PubMed1997

Setting handicap goals with elderly people: a pilot study of the Life Strengths Interview.

OBJECTIVE: To assess whether the Life Strengths Interview (LSI) is a useful clinical framework to identify handicap goals. DESIGN: Clinical case studies. SETTINGS: Two elderly care rehabilitation hospitals. SUBJECTS: Five people, whose ages ranged from 73 to 90 years. All participants were aware of their likely resultant disability, scored 25+ out of a possible 30 with the Mini-Mental State Examination, were able to communicate effectively and were due to be discharged home in approximately one month. INTERVENTIONS: Each participant undertook the LSI process with the research occupational therapist. MAIN OUTCOME MEASURES: Identified rehabilitation goals and their achievement. RESULTS: Goals were focused around families and other support networks. Six to eight weeks following discharge, achievement of goals varied. CONCLUSIONS: This pilot study suggests that the LSI may be a useful clinical framework but further research needs to investigate whether a modified clinical version may be more suitable.

Activities of Daily Living↗

PubMed2025

MO-GCAN: multi-omics integration based on graph convolutional and attention networks.

MOTIVATION: Cancer subtypes play a critical role in disease progression, prognosis, and treatment, making their detection essential for tailoring precision medicine. Studies have shown that multi-omics integration outperforms single-omics approaches in cancer subtyping tasks. However, due to the high-dimensionality of multi-omics data, many existing studies either fail to capture the correlation between true labels and learned features, or lack sufficient capacity to model complex biological representations. These limitations hinder the full potential of leveraging the rich and complementary information embedded in multi-omics datasets. RESULT: We propose a framework that leverages supervised feature learning and classification based on a graph-based learning approach with attention mechanism for cancer subtyping. More specifically, we train graph convolutional network models on each omics dataset to extract latent representations, which are then concatenated to form a comprehensive multi-omics feature embedding. We further develop sample fusion network based on the omics-specific graphs, incorporating the derived features and feeding them into a graph attention model for subtype classification. This two-stage multi-omics framework is applied to eight cancer types, with performance evaluated in terms of test accuracy, training time, macro-averaged precision, recall, and F-score. Experimental results show that the proposed method outperforms state-of-the-art approaches across various cancer types. Additionally, we provide empirical evidence supporting the hypothesis that retaining a limited number of high-confidence edges and utilizing enriched embeddings from intermediate graph neural network layers can improve predictive performance. AVAILABILITY AND IMPLEMENTATION: Data and the code are available at https://github.com/YD-00/MO-GCAN-Updated.git.

Neoplasms↗

PubMed1991

[Transcultural validation of a measurement scale].

This monography presents the validation study results of a new scale to measure family needs: The Family Needs Inventory (IBF) (Chartier and Coutu-Wakulczyk, 1988). The scale is available in both French and English from the Departement des sciences infirmières of the Université de Sherbrooke. Based on a perceptual framework, the IBF is a self-report scale composed of 33 items. It offers three different subscores of the importance of needs: the global score of needs, the intensity need index and the total number of needs. The IBF was validated on a sample of 400 subjects. These subjects were drawn from the adult population of immediate family members visiting a patient in surgical or medical intensive care units in three different geographical regions, in Québec, northeast Ontario and France. The reliability yielded a 0.90 Cronback Alpha coefficient and the homogeneity coefficient for Spearman-Brown and Guttman procedures were 0.88 respectively. The principal component factor analysis and factorial matrices lead to examine the conceptual structure of five independent factors.

Cross-Cultural Comparison↗

PubMed1995

"Healthy Dubec" -design of a joint Czech-American community project for the reduction of cardiovascular and cerebrovascular disease (adapted from American experience).

The project is a combination of individual and community-based intervention which adapted and modified methods and techniques originally used in The Three-City Community Study and The Stanford Five-City Project in a small community outside Prague. The goal is to reduce cardiovascular and cerebrovascular risk factors by primary and secondary prevention, using a community-based approach. 61.5% of examined population with the low risk score during the baseline survey was exposed to intervention by community-based methods. 38.5% of adult population was included in intervention activities within the framework of secondary prevention in high risk groups. There are described: the method of community oriented intervention and the intervention oriented on high risk groups - nutrition intervention, quit smoking activities, stress control, physical activity promotion.

Adolescent↗

PubMed2026

Prostate Cancer, Genetic Susceptibility, and Risk of Chronic Non-Urological Complications.

BACKGROUND: Chronic nonurological complications are common among prostate cancer (PCa) survivors; however, their spectrum, magnitude, and genetic contribution remain poorly characterized. METHODS: We evaluated 15 commonly reported nonurological complications and tested their associations with exposure to PCa and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N = 219,133). Analyses were conducted using cause-specific Cox proportional-hazards models within a full-cohort framework with time-updated PCa status, delayed entry at study recruitment, and age as the underlying time scale. RESULTS: After recruitment, incident PCa was diagnosed in 13,780 men, of which 1,656 (12.02%) had metastatic PCa (mPCa). Risks for seven complications were higher among men with PCa, adjusting for genetic background (all p < 0.05), including osteoporosis, venous thromboembolism, depression, and four primary cancers (bladder, kidney, colorectal, and pancreatic). Risks were consistently stronger among men exposed to mPCa than non-mPCa; for example, the hazard ratio (HR) (95% confidence interval) for osteoporosis was 1.88 (1.63-2.18) for any PCa, 4.67 (3.11-7.01) for mPCa, and 1.75 (1.50-2.04) for non-mPCa. Elevated risks for three additional complications (coronary artery disease, type 2 diabetes and chronic obstructive pulmonary disease) were observed only among men with mPCa. The risks for these ten complications were further increased among men with higher disease-specific PRS; for example, the HR for osteoperosis in mPCa patients in the top PRS quartile was 13.57 (8.24-22.34) compared with men without PCa (p < 0.001). CONCLUSION: PCa diagnosis and inherited genetic susceptibility jointly contribute to increased risks of multiple chronic non-urological complications among survivors.

Humans↗

PubMed2026

Beyond exons: Linking noncoding heritability and polygenicity across complex human traits and disorders.

The genetic architecture of complex traits spans a continuum of polygenicity, yet it remains unclear how differences in polygenicity relate to the functional localization of SNP heritability across the genome. We use a MiXeR-based framework to partition heritability across 74 functional annotations covering exonic, intronic, and intergenic regions for 34 complex traits and introduce a likelihood-based annotation contribution score that quantifies annotation-specific impact on heritability. Exons account for a minority of heritability, and their contribution decreases with increasing polygenicity, from an average of 22% in less-polygenic somatic diseases and biomarkers to 13% in highly polygenic psychiatric and cognitive phenotypes. Intergenic fractions show the opposite trend, whereas intronic fractions remain relatively stable. Analysis of the broader set of functional annotations also reveals systematic differences along the polygenicity axis: highly polygenic traits show stronger contributions from comparative genomics and variant-effect scores, whereas less-polygenic traits show stronger contributions from promoter, transcription, and chromatin annotations. Together, these results indicate that the functional partitioning of heritability systematically varies with polygenicity, shifting from gene-proximal regulatory architectures to architectures shaped by numerous dispersed regulatory effects.

MiXeR↗

PubMed2026

Graph-KIR: graph-based KIR copy number estimation and allele calling using short-read sequencing data.

MOTIVATION: The Killer-cell Immunoglobulin-like Receptor (KIR) is a highly polymorphic region in the human genome, associated with autoimmune diseases and organ transplantation. The sequences of KIR genes are highly similar among star alleles as well as in between individual genes, with the copy number of each KIR gene typically ranging from 0 to 4. In this study, we introduce Graph-KIR, a tool designed to estimate gene copy numbers and predict full-resolution (7-digit, encompassing both coding and non-coding sequence variations) from a whole genome sequencing (WGS) sample. RESULTS: Graph-KIR is capable of independently typing KIR alleles per sample with no reliance on the distribution of any framework gene in a cohort. In a set of 100 simulated samples, Graph-KIR demonstrated 99.2% accuracy in copy number estimation and high F1-score of allele typing: 91.79% at 7-digit resolution, 97.37% at 5-digit resolution, and 97.11% at 3-digit resolution. Graph-KIR outperforms existing tools such as Geny (96.39% F1-score), PING's WGS version (92.77% F1-score), and T1K (90.44% F1-score) at 5-digit resolution. By analyzing the results on 44 HPRC samples, Graph-KIR achieves better F1-score than Geny and PING at 7-digit resolution. The release of Graph-KIR adds another valuable tool to assist users in accurately estimating copy numbers and calling alleles of KIR genes from WGS samples. AVAILABILITY AND IMPLEMENTATION: The Graph-KIR and paper-related pipeline codes are available at https://github.com/linnil1/KIR_graph.

Receptors, KIR↗

PubMed2026

Genetic risk stratification of common diseases in breast cancer survivors: a population-based cohort study.

IMPORTANCE: Patients diagnosed with breast cancer (BCa) are at increased risk of multiple common diseases; however, the spectrum of these diseases and the contribution of inherited genetic susceptibility remain incompletely characterized. METHODS: We evaluated 15 common diseases and tested their associations with BCa exposure and disease-specific polygenic risk scores (PRS) in the UK Biobank (UKB; N = 254,736). Analyses were performed using cause-specific Cox proportional hazards models within a full-cohort framework, with time-updated BCa status, delayed entry at study recruitment, and age as the underlying time scale. RESULTS: After recruitment, incident BCa was diagnosed in 11,386 women (4.47%), including 2,742 (24.08%) with metastatic BCa. Patients with BCa had an increased risk of nine diseases spanning cardiovascular, metabolic, and neuropsychiatric domains (P<0.003, Bonferroni-corrected). Elevated risks were generally observed among patients with both early staged and advanced BCa. Inherited susceptibility further stratified disease risk, with the highest risks observed among patients with BCa with elevated disease-specific PRS. For example, compared with women without BCa, the hazard ratio (HR; 95% CI) for osteoporosis was 2.33 (2.15-2.52) among women with any BCa, 2.38 (2.18-2.59) among those with non-metastatic BCa, and 2.12 (1.78-2.54) among those with metastatic BCa; the HR was 4.48 (3.99-5.02) among patients with BCa in the highest quartile of osteoporosis-specific PRS (all P<0.001). In contrast, BCa was not significantly associated with risk of coronary artery disease. CONCLUSION: BCa and inherited genetic susceptibility jointly contribute to increased risk of multiple common diseases, supporting the integration of genetic risk stratification into survivorship care.

Complications↗

PubMed1975

Communicative behavior in schizophrenia. The relation of adaptive styles to kinetic and linguistic aspects of interview behavior.

Recent studies of formal kinetic and linguistic aspects of communication suggest that these may be important signposts of internal processes responsible for the regulation and organization of verbal thought. If so, the formal analysis of communication patterns of patients known to have difficulty in cognitive organization (chronic schizophrenics) should reveal kinetic and linguistic characteristics consistent with their level of adaptive cognitive functioning. In the present study, 16 chronic nonparanoid schizophrenic patients were video recorded during a clinical interview, and their kinetic and linguistic behavior was analyzed according to systems developed in our laboratory. Eight of these patients were chronic, isolated patients, classified by means of a scale for measuring proneness to future hospitalization, as extremely "prone" to rehospitalization, and eight were chronic, overtly oppositional patients, classified as "nonprone" to hospitalization. Prone patients are known to exhibit a relatively impoverished form of cognitive functioning, while nonprone patients exhibit more highly differentiated cognitive functioning. The major findings of this study revealed that the isolated prone patients could be distinguished from the nonprone patients, in their communicative behavior, by an increased utilization of the most repetitive and unpatterned stimulation of body parts, as well as the most simple form of linguistic narration of experience. The oppositional nonprone patients more often utilized circumscribed, patterned, and brief kinetic stimulation of body parts, as well as a form of language construction characterized by a complex conditional (i.e., causal, deductive, or purposive) framework for the expression of thought. In addition, social and affective components of the scale measuring hospital proneness were related to our formal kinetic and linguistic scoring categories. An explanation of these findings was offered based upon the well documented relationship observed in the literature between isolation and hyperarousal in chronic schizophrenia. That is, an attempt was made to integrate these findings with the notion that the schizophrenic disorder reflects an integrative deficit which is regulated by increasing the magnitude of proprioceptive feedback (and hence, arousal) through stereotyped repetitive motor activity.

Adaptation, Psychological↗

PubMed2025

ProgModule: A novel computational framework to identify mutation driver modules for predicting cancer prognosis and immunotherapy response.

BACKGROUND: Cancer originates from dysregulated cell proliferation driven by driver gene mutations. Despite numerous algorithms developed to identify genomic mutational signatures, they often suffer from high computational complexity and limited clinical applicability. METHODS: Here, we presented ProgModule, an advanced computational framework designed to identify mutation driver modules for cancer prognosis and immunotherapy response prediction. In ProgModule, we introduced the Prognosis-Related Mutually Exclusive Mutation (PRMEM) score, which optimizes the balance between exclusive mutation coverage and the incorporation of mutation combination mechanisms critical for cancer prognosis. RESULTS: Applying to BLCA and HNSC cohorts, ProgModule successfully identified driver modules that stratify patients into distinct prognostic subgroups, and the combination of these modules could serve as an effective prognostic biomarker. Extending our method to diverse cancers, ProgModule presented robust prognostic performance and stability across model parameters, including stopping criteria and network topology. Moreover, our analysis suggested that driver modules can predict immunotherapeutic benefit more effectively than existing signatures. Further analyses based on published CRISPR data indicated that genes within these modules may serve as potential therapeutic targets. CONCLUSIONS: Altogether, ProgModule emerges as a powerful tool for identifying mutation driver modules as prognostic and immunotherapy response biomarkers, and genes within these modules may be used as potential therapeutic targets for cancer, offering new insights into precision oncology.

Humans↗

PubMed2026

Effects of different training modalities on lower-limb explosive power, acceleration, 20-m sprint performance, and change-of-direction ability in youth soccer players: a systematic review and network meta-analysis.

BACKGROUND: Youth soccer players repeatedly perform explosive actions, short accelerations, linear sprints, decelerations, and multidirectional movements. However, the comparative effects of different structured physical-conditioning programmes remain uncertain. METHODS: Seven databases were searched from inception to 3 July 2026 using a final expanded search strategy encompassing plyometric, strength or resistance, sprint, acceleration, speed, change-of-direction, neuromuscular, multicomponent, and combined training. Randomised controlled trials involving healthy youth soccer players were eligible. Intervention arms were classified using operational, content-based node definitions. Construct-restricted primary networks and expanded sensitivity networks were analysed using frequentist random-effects network meta-analysis. Hedges' adjusted g was preferentially calculated from post-intervention or final-follow-up means, standard deviations, and sample sizes. Estimates were presented so that positive values indicated better performance. P-scores were treated as descriptive ranking summaries. Risk of bias was assessed using an adapted study-level application of the five-domain RoB 2 framework, and confidence in the evidence was assessed using CINeMA. A post hoc strict-age sensitivity analysis excluded two age-boundary studies. RESULTS: Eighty-nine studies were included in the expanded quantitative analysis, of which 74 contributed to at least one construct-restricted primary network. The primary lower-limb explosive-power, acceleration, 20-m sprint, and planned change-of-direction networks included 55, 20, 25, and 38 studies, respectively. Compared with usual soccer training, plyometric training combined with sprint and/or change-of-direction training showed favourable estimates for lower-limb explosive power (SMD 0.79, 95% CI 0.55 to 1.03), acceleration (1.19, 0.90 to 1.49), 20-m sprint performance (0.80, 0.33 to 1.28), and planned change-of-direction ability (1.46, 1.13 to 1.80). Corresponding I² values were 34.6%, 21.8%, 65.0%, and 41.0%. Between-design inconsistency was detected in the 20-m sprint (P = 0.0036) and change-of-direction (P = 0.0007) networks. CINeMA confidence for these four comparisons was low, low, very low, and low, respectively. Expanded sensitivity networks showed substantially greater heterogeneity. The highest-ranked intervention differed across outcome domains but remained consistent within each outcome across the three analysis sets. Excluding the two age-boundary studies did not materially alter the principal estimates. CONCLUSIONS: Plyometric training combined with sprint and/or planned change-of-direction training produced favourable comparative estimates across the four performance outcomes. However, evidence for several nodes and active-versus-active comparisons was sparse, heterogeneity in programmes and outcomes was present, inconsistency was detected in some networks, and confidence in the evidence was low or very low. These limitations do not support a conclusion that any training category is universally superior. The findings should be interpreted as provisional category-level signals rather than definitive training prescriptions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420261347297, registered on 21 March 2026, https://www.crd.york.ac.uk/PROSPERO/view/CRD420261347297 .

Change-of-direction ability↗

PubMed1996

Effects of induced mood states on objective and projective dependency scores.

In two experiments involving a total of 144 participants (72 women and 72 men), we examined the effects of induced mood states on college students' scores on widely used objective and projective measures of dependency. In both experiments, induced mood states significantly influenced participants' scores on the projective dependency test but did not affect their scores on the objective dependency test. Findings are discussed in the context of previous studies comparing objective and projective dependency measures and with respect to theoretical frameworks that distinguish implicit from self-attributed dependency needs.

Adult↗

PubMedDate not supplied

Designing self-report instruments for family assessment.

As family medicine research expands, more and better self-report measures for quantifying family systems variables will be required. These measures should be developed from an accepted paradigm for instrument design that includes the following. They should be: 1) grounded in a contemporary conceptual framework; 2) constructed following a rational theoretical design that includes the sequential stages of construct identification, construct definition, item generation, item editing, item formatting, and item scoring; 3) analyzed empirically at the item level for item distribution characteristics, item-scale correlation, and item-response style correlations; 4) analyzed at the scale level for scale distribution characteristics, scale-scale correlations, and scale-response style correlation; 5) revised based on editing and empirical analysis; and 6) psychometrically evaluated for reliability (eg, internal consistency, test-retest) and validity (construct related, criterion related, and content related). Normative data from various reference populations must also be obtained to provide a basis for interpreting scores. Finally, test manuals must be written to summarize test development data and provide information on administration procedures, scoring, and interpretation.

Behavior↗

PubMed2026

Multi-Omics Integration Identifies a Five-Gene Metabolic Signature With Experimental Validation in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is hallmarked by profound metabolic reprogramming; however, its intricate crosstalk with the tumor immune microenvironment (TIME) and its clinical ramifications remain inadequately elucidated. This study aims to systematically decipher the metabolic-immune interplay in ccRCC through multi-omics integration, with the goal of identifying robust prognostic biomarkers and actionable therapeutic vulnerabilities. AIMS: This study aims to systematically decipher the metabolic-immune interplay in clear cell renal cell carcinoma (ccRCC) through multi‑omics integration, and to identify robust prognostic biomarkers and actionable therapeutic vulnerabilities that can inform precision risk stratification and individualized treatment strategies. METHODS: We integrated bulk transcriptomic, genomic, and clinical data from multiple ccRCC cohorts. Differential expression and functional enrichment analyses were performed to characterize metabolic pathway alterations. Mendelian randomization (MR) was employed to infer causal relationships between metabolic disorders and ccRCC risk. A machine learning-based prognostic framework, incorporating SHAP (SHapley Additive exPlanations) for feature interpretability, was constructed and rigorously validated. TIME heterogeneity was dissected using deconvolution algorithms, while drug sensitivity, tumor mutation burden (TMB), and TIDE scores were utilized to assess therapeutic responses and immune evasion. Candidate gene function was evaluated through in vitro gain- and loss-of-function assays, with expression validated via TCGA, HPA, western blot, and qRT-PCR. RESULTS: Enrichment analysis identified coordinated dysregulation in lipid metabolism, energy homeostasis, and hypoxia response pathways. MR analysis confirmed lipid metabolism disorders as a causal risk factor for ccRCC. Our machine-learning model, centered on five core SHAP-identified features (SUCLA2, ACAT1, PC, SUCLG1, and HMGCS2), demonstrated superior predictive accuracy over conventional clinical staging. Immune profiling unveiled dichotomous TIME states: the low-risk group retained active immune surveillance, whereas the high-risk group was enriched with immunosuppressive subsets. Drug sensitivity screening pinpointed LY2109761 and carmustine as high-risk-specific candidate agents. Furthermore, TMB and TIDE analyses stratified high-risk patients displaying genomic instability and immune evasion phenotypes. Functionally, SUCLA2 knockdown significantly enhanced ccRCC cell proliferation and invasion, while its overexpression suppressed these malignant phenotypes, corroborating its tumor-suppressive role. Expression patterns of the hub genes were consistently validated across multi-level datasets and experimental assays. CONCLUSION: This study establishes a precision oncology framework for ccRCC by functionally linking metabolic biomarkers, immunophenotypes, and stratified therapeutic strategies. Importantly, we identify SUCLA2 as a potential functional tumor suppressor and a promising target for further mechanistic and translational investigation.

Humans↗

PubMed1980

Precision of histological grading of malignancy.

The precision of a grading system based upon average score of 8 items for histological evaluation of malignancy of epidermoid carcinomas of the larynx was studied by letting 6 pathologists examine biopsies from 22 new cases. Exploratory statistical tools as well as a statistical framework (variance component models) for separating and evaluating the noise components are suggested. The order of magnitude of the resulting overall measurement uncertainty allowed discrimination between patients, though if a patient is graded by only one pathologist, only results as the extremes of the scale of malignancy should be trusted as possible therapeutical guidance. Based upon an analysis of the basic structure of the grading system the single noise components making up the measurement uncertainty were determined. Of greatest importance was noice created by disagreement between the pathologists in their ranking of the patients on the scale of malignancy. Furthermore the pathologist used the individual items differently, and certain items seemed to conform little to the scoring system. An attempt to minimize these two last components was performed; however neither calibration of the pathologists nor omission of the deviating items improved the precision significantly.

Carcinoma, Squamous Cell↗