Measuring and Validating a General Cancer Predisposition Perception Scale: An Adaptation of the Revised-IPQ-Genetic Predisposition Scale

Background

Illness perceptions are linked to individual help-seeking and preventive behaviors. Previous illness perception studies have identified five dimensions of illness-related experience and behaviour. The Revised Illness Perception Questionnaire (IPQ-R) for genetic predisposition (IPQ-R-GP) was developed to measure illness perceptions in those genetically-predisposed to blood disease. We adapted the IPQ-R-GP to measure perceptions of generalized cancer predisposition. This paper describes the development and validation of the Cancer Predisposition Perception Scale (CPPS).

Methods

The draft CPPS scale was first administered to 167 well Hepatitis B carriers and 123 other healthy individuals and the factor structure was examined using Exploratory Factor Analysis. Then the factor structure was confirmed in a second sample comprising 148 healthy controls, 150 smokers and 152 passive smokers using Confirmatory Factor Analysis (CFA).

Results

Six-factors comprising 26 items provided optimal fit by eigen and scree-plot methods, accounting for 58.9% of the total variance. CFA indicated good fit of the six-factor model after further excluding three items. The six factors, Emotional representation (5 items), Illness coherence (4 items), Treatment control (3 items), Consequences (5 items), Internal locus of control (2 items) and External locus of control (4 items) demonstrated adequate-to-good subscale internal consistency (Cronbach’s α = 0.63–0.90). Divergent validity was suggested by low correlations with optimism, self-efficacy, and scales for measuring physical and psychological health symptoms.

Conclusion

The CPPS appears to be a valid measure of perceived predisposition to generic cancer risks and can be used to examine cancer-risk-related cognitions in individuals at higher and lower cancer risk.     

Individual differences in selecting patients for regular haemodialysis.

Eight clinicians in a renal dialysis unit were asked to classify the suitability of 100 cases (some real, some simulated) for regulat haemodialysis. Seven categories were used, ranging from "excellent prospect: accept without reservation" to "unequivocal rejection," based on 18 items of information previously agreed on as sufficient for the purpose. The ways in which they classified the cases different considerably; only six cases were placed in the same category by all eight clinicians, and this was the "unequivocal rejection" category. Analysis of the extent to which they made effective use of the items showed that between three and nine items were used to a sufficient extent to reach significance for the 100 cases.     

An Assessment of Cumulative Classification

We present a method for building systematics when new knowledge is continuously accumulated. The resulting classification is self-correcting and improves itself by sorting new items as they are added to the material and studied. The formulation is based on Bayesian predictive probability distributions. A new item that has not yet been classified is assigned to the class that has maximal posterior probability or is made to form a group of its own. Such a cumulative classification depends on the order in which the items are classified. The introduction of an already classified training set considerably improves the repeatability of the method. As a case study we applied the method to a large data set for the Enterobacteriaceae. The resulting classifications corresponded well to the general structure of the prevailing taxonomy of Enterobacteriaceae.     

基于医疗成本项目标准化核算的成本控制研究

首先对医疗成本项目进行分类标准化处理，统一和规范医疗作业成本项目；在此基础上借助作业成本法，通过对医疗项目的价值分析与优化，达到节约卫生资源，控制医疗成本的目的；最后，通过实例和数学模型证明医疗成本项目标准化核算下的医疗成本控制的有效性。     

One-Year Mortality in Older Patients with Cancer: Development and External Validation of an MNA-Based Prognostic Score

Purpose

The MNA (Mini Nutritional Assessment) is known as a prognosis factor in older population. We analyzed the prognostic value for one-year mortality of MNA items in older patients with cancer treated with chemotherapy as the basis of a simplified prognostic score.

Methods

The prospective derivation cohort included 606 patients older than 70 years with an indication of chemotherapy for cancers. The endpoint to predict was one-year mortality. The 18 items of the Full MNA, age, gender, weight loss, cancer origin, TNM, performance status and lymphocyte count were considered to construct the prognostic model. MNA items were analyzed with a backward step-by-step multivariate logistic regression and other items were added in a forward step-by-step regression. External validation was performed on an independent cohort of 229 patients.

Results

At one year 266 deaths had occurred. Decreased dietary intake (p = 0.0002), decreased protein-rich food intake (p = 0.025), 3 or more prescribed drugs (p = 0.023), calf circumference <31cm (p = 0.0002), tumor origin (p<0.0001), metastatic status (p = 0.0007) and lymphocyte count <1500/mm³ (0.029) were found to be associated with 1-year mortality in the final model and were used to construct a prognostic score. The area under curve (AUC) of the score was 0.793, which was higher than the Full MNA AUC (0.706). The AUC of the score in validation cohort (229 subjects, 137 deaths) was 0.698.

Conclusion

Key predictors of one-year mortality included cancer cachexia clinical features, comorbidities, the origin and the advanced status of the tumor. The prognostic value of this model combining a subset of MNA items and cancer related items was better than the full MNA, thus providing a simple score to predict 1-year mortality in older patients with an indication of chemotherapy.     

Implications of absence of measurement invariance for detecting sex limitation and genotype by environment interaction.

Using univariate sum scores in genetic studies of twin data is common practice. This practice precludes an investigation of the measurement model relating the individual items to an underlying factor. Absence of measurement invariance across a grouping variable such as gender or environmental exposure refers to group differences with respect to the measurement model. It is shown that a decomposition of a sum score into genetic and environmental variance components leads to path coefficients of the additive genetic factor that are biased differentially across groups if individual items are non-invariant. The arising group differences in path coefficients are identical to what is known as "scalar sex limitation" when gender is the grouping variable, or as "gene by environment interaction" when environmental exposure is the grouping variable. In both cases the interpretation would be in terms of a group-specific effect size of the genetic factor. This interpretation may be incorrect if individual items are non-invariant.     

Classifying microRNAs in cancer: the good, the bad and the ugly

MicroRNAs (miRNAs) have quite recently emerged as a novel class of gene regulators. Many miRNAs exhibit altered expression levels in cancer, and we are only starting to understand the functional consequences of the loss or gain of particular miRNAs to the cancerous phenotype. miRNAs can be classified with regard to their role in cancer as the Good, the Bad and the Ugly. The "Good", those miRNAs that are innocent bystanders in the oncogenic transformation process, whose expression profile might even be used for cancer diagnosis or prognosis. The "Bad", those miRNAs that are causally linked to tumorigenesis and directly modify tumor suppressor- or oncogenic- pathways. And the "Ugly", those miRNAs whose inappropriate loss or gain destabilizes the cellular identity of a tumor, which indirectly results in enhanced phenotypic variability and progression of the tumor. Hereunder we will discuss the possible ways in which miRNAs can be relevant to cancer biology, and possible experimental strategies for elucidating the mechanisms involved.     

Developing a wetland-type classification system in the Republic of Korea

Though there are wetlands listed by the IUCN and wetland protection areas designated by the government, it is presumed that there would be more wetlands in Korea when they are surveyed and classified according to international wetland criteria, but a considerable amount of area is yet to be identified. Therefore, in order to conduct a systematic status survey on the wetlands of Korea, a wetland classification system needs to be developed first. The objectives of this paper include reviewing international wetland classifications and mapping systems of the USA, Germany, the Netherlands, Japan and North Korea and developing a wetland classification and mapping system appropriate to Korea based on an understanding of the major case examples of wetland types. Then, the developed system was applied to the Phanmun field watershed located at the western DMZ in Korea to conduct a case study. The overall process of a wetland classification and mapping system developed in this study is undertaken as the following from step 1 to step 5. First, wetlands are identified based on three parameters: hydrology, hydrophytes and hydric soil. Second, wetland delineation distinguished wetland areas and non-wetland areas by identifying wetlands through a field survey. Third, an ecological survey is conducted in order to classify wetland characteristics and types for the target area. Ecological survey items include the topography, landscape, biota, pollutant sources and land use status. Fourth, a wetland classification is developed through a hybrid approach based on HGM (the hydrogeomorphic method). Level 1 is classified into inland, estuarine and costal areas. Level 2, the target area, is classified as an eco-region at a watershed level, and level 3 is classified into depression, riverine, slope, flat and fringe areas based on a HGM approach. Level 4 is classified into detailed wetland types based on specific characteristics of wetlands. Level 5 is classified into marsh and swamp based on grasslands and shrubs and forest trees. Level 6 indicates the dominant vegetation communities.

Lighting during the day and night: possible impact on risk of breast cancer

Risk of breast cancer varies by about 5-fold among societies, and incidence and mortality have been increasing worldwide for many decades. Migrants from low-risk Asian societies to the U.S. suffer elevated risk of breast cancer in their own lifetimes, and the second or third generation Asian-Americans attain the high risk of the multi-generational European immigrants [1,2]. Something about a modern Western lifestyle apparently increases risk dramatically. Madigan et al. [3] estimate that 41% of the new U.S. cases of breast cancer are explained by "known risk factors"; these include the reproductive factors of age at first birth, menarche, menopause. They ascribe about 30% to reproductive factors when they are analyzed alone. "High income" is estimated to account for about 19% when analyzed by itself. The 41% is an analysis taking all the factors together, and since they are related, the total is less than the sum of estimates for the individual items. By itself, "High income" has no biological interpretation and must reflect attributes of lifestyle and/or environment that increase risk. So, the proportion of breast cancer cases in the U.S. that can be accounted for by known biological risk factors is about one third. Therefore, at least half of breast cancer risk in the U.S., and other Westernized/industrialized societies, is in excess of that found in non-industrialized societies and is without any agreed-upon explanation. Many candidate factors exist, each with a cadre of proponents. The sum of these may turn out to explain the bulk of the excess risk in modern societies. On the other hand, they may not, and worse, may fall woefully short.     

Multistep renal carcinogenesis as gene expression disease in tumor suppressor TSC2 gene mutant model--genotype, phenotype and environment

Cancer is an inheritable disorder of somatic cells. Environment and heredity both operate in the origins of human cancer. These environmental and genetic determinants of cancer can be classified into four groups designated "Oncodemes" [1].Oncodeme 1 is the irreducible "background" level of cancer due to spontaneous mutagenesis. Oncodeme 2 is "environmentally induced" cancer, whose causative agents are chemical carcinogens, radiation and viruses. Oncodeme 3 is basically "environmentally induced" cancer, but there are genetically determined differences among persons, e.g. the activation or inactivation of carcinogenes. Most human cancers are believed to belong to Oncodemes 2 and/or 3 (about 80%), for which the probability of the occurrence of the initial carcinogenic step(s) is increased, although the number of steps is not decreased. Oncodeme 1 would contain the approximately 20% that would remain if "environmentally induced" cancers (Oncodeme 2 and/or 3) were prevented. Lastly, Oncodeme 4 is "hereditary" cancer. Hereditary cancers could prove valuable in elucidating carcinogenesis, even though only a small proportion of cancers belong to this group. Here, we present a unique animal model of Oncodeme 4 for the study of problems in carcinogenesis; e.g. cell stage and tissue/cell-type-specific tumorigenesis, multistep carcinogenesis, species-specific differences in tumorigenesis, modifier gene(s) in renal carcinogenesis and cancer prevention.     

Gutsy genetics: identification of digested piscine prey items in the stomach contents of sympatric native and introduced warmwater catfishes via DNA barcoding

A major focus of ecology is understanding trophic relationships and energy flows in natural systems, associated food web dynamics and changes in food webs due to introduced species. Predator-prey interactions are often assessed by examining stomach contents. However, partially digested remains may be difficult to accurately identify by traditional visual analysis. Here we evaluate the effectiveness of DNA barcoding to identify digested piscine prey remains in invasive Blue Catfish Ictalurus furcatus, non-native, but established Channel Catfish Ictalurus punctatus and native White Catfish Ameiurus catus from Chesapeake Bay, USA. Stomach contents were examined and piscine prey items were scored as lightly digested, moderately digested or severely digested. A 652 base pair region of the cytochrome c oxidase subunit I (COI-5P) mitochondrial DNA gene was sequenced for each prey item. Edited barcode sequences were compared to locally-caught and validated reference sequences in BOLD (Barcode of Life Database). A large majority of prey items were sufficiently digested to limit morphological identification (9.4 % to species and an additional 12.1 % to family). However, overall barcoding success was high (90.3 %) with little difference among the digestion classifications. Combining morphological and genetic identifications, we classified 91.6 % of fish prey items to species. Twenty-three fish species were identified, including species undergoing active restoration efforts (e.g., Alosa spp.) and commercially important species, e.g., Striped Bass Morone saxatilis, White Perch Morone americana, American Eel Anguilla rostrata and Menhaden Brevoortia tyrannus. We found DNA barcoding highly successful at identifying all but the most heavily degraded prey items and to be an efficient and effective method for obtaining diet information to strengthen the resolution of trophic analyses including diet comparisons among sympatric native and non-native predators.     

Raised serum urate concentration as risk factor for premature mortality in middle aged men: relation to death from cancer.

Low serum cholesterol concentrations are associated with deaths from cancer. This association was found in a prospective study of middle aged men in Malmö and consideration of possible explanations for the lowering of serum cholesterol prompted an analysis of serum urate in relation to deaths from cancer. A total of 127 of the 7725 participants in the Malmö study had died since screening. A weakly positive but significant correlation between raised serum urate concentration and total mortality was found. This correlation was wholly explained by neoplastic deaths (p less than 0.01), while there were no associations with alcohol related deaths or with deaths from coronary heart disease. When the deaths from cancer were classified as "early" or "late"--that is, occurring less than or more than 2.5 years after the screening--the correlation between raised urate concentrations and cancer mortality was confined to the "early" deaths (p less than 0.001). Further studies are needed to substantiate the relation between raised serum urate concentrations and fatal neoplasia. Nevertheless, these findings weigh against recent suggestions that uric acid has an antioxidant protective effect against cancer.     

Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function

Over 520 different amino acid substitution variants have been previously identified in the systematic screening of 91 human DNA repair genes for sequence variation. Two algorithms were employed to predict the impact of these amino acid substitutions on protein activity. Sorting Intolerant from Tolerant (SIFT) classified 226 of 508 variants (44%) as "Intolerant." Polymorphism Phenotyping (PolyPhen) classed 165 of 489 amino acid substitutions (34%) as "Probably or possibly damaging." Another 9-15% of the variants were classed as "Potentially intolerant or damaging." The results from the two algorithms are highly associated, with concordance in predicted impact observed for approximately 62% of the variants. Twenty-one to thirty-one percent of the variant proteins are predicted to exhibit reduced activity by both algorithms. These variants occur at slightly lower individual allele frequency than do the variants classified as "Tolerant" or "Benign." Both algorithms correctly predicted the impact of 26 functionally characterized amino acid substitutions in the APE1 protein on biochemical activity, with one exception. It is concluded that a substantial fraction of the missense variants observed in the general human population are functionally relevant. These variants are expected to be the molecular genetic and biochemical basis for the associations of reduced DNA repair capacity phenotypes with elevated cancer risk.     

Life history of <Emphasis Type="Italic">Gymnotus refugio</Emphasis> (Gymnotiformes; Gymnotidae): an endangered species of weakly electric fish

The present study describes the life history of Gymnotus refugio, a species classified as Endangered in the last published list of threatened species of the Brazilian fauna. The study was conducted at a conservation unity that protect one of the last remaining semideciduous forests in the region. The reproductive period was estimated as occurring from the end of winter to the last summer months. Gymnotus refugio exibited fractional spawning, the lowest relative fecundity registered among the Gymnotifomes species studied at the present, and male parental care behavior. The analyses showed a seasonal pattern on the species diet, associating different food categories to winter, autumn, and spring. According to food items analysis and estimated intestinal quotient, G. refugio was classified as invertivorous, feeding mainly on autochthonous insects. The results obtained herein suggest that the position of G. refugio as an Endangered species might be influenced by its territoriality, habitat specificity, parental care behavior, and low fecundity, reinforcing the importance of swampy forest environment conservation as the only means of the species maintenance.     

Genome-wide analysis of organ-preferential metastasis of human small cell lung cancer in mice

Although a number of molecules have been implicated in the process of cancer metastasis, the organ-selective nature of cancer cells is still poorly understood. To investigate this issue, we established a metastasis model in mice with multiple organ dissemination by i.v. injection of human small cell lung cancer (SBC-5) cells. We analyzed gene-expression profiles of 25 metastatic lesions from four organs (lung, liver, kidney, and bone) using a cDNA microarray representing 23,040 genes and extracted 435 genes that seemed to reflect the organ specificity of the metastatic cells and the cross-talk between cancer cells and microenvironment. Furthermore, we discovered 105 genes that might be involved in the incipient stage of secondary-tumor formation by comparing the gene-expression profiles of metastatic lesions classified according to size (<1 or >2 mm) as either "micrometastases" or "macrometastases." This genome-wide analysis should contribute to a greater understanding of molecular aspects of the metastatic process in different microenvironments, and provide indicators for new strategies to predict and prevent metastasis.     

Defining a molecularly normal colon.

As techniques evolve that allow molecular characterization of disease processes such as cancer, definition of "normal" at a molecular level becomes increasingly important. Increasingly large numbers of mutations are found at the genomic level, but whether all of those mutations contribute to the malignant state of a carcinoma cell is not clear. Without knowledge of what constitutes normality on the proteomic level in an organ or cell, we cannot determine what genomic changes are physiologically important. Traditionally, colon cancer is identified and classified by histological criteria. Margins of the colon are defined as "grossly uninvolved" when the histology is indistinguishable from that of normal (free from disease) colon. By using molecular pathology techniques and working backward from colon adenocarcinoma to hypoplastic polyps to presumably normal mucosa, we defined some of those protein differences. Our results may provide a molecular basis for identifying tumor formation and progression in situ.(J Histochem Cytochem 49:667-668, 2001)     

Is communication improving between general practitioners and psychiatrists?

General practitioners and psychiatrists communicate mainly by letter. To ascertain the most important items of information that should be included in these letters ("key items") questionnaires were sent to 80 general practitioners and 80 psychiatrists. A total of 120 referral letters sent to psychiatric clinics in 1973 and 1983 were studied, together with the psychiatrists'' replies, and these were rated for the inclusion of "key items." General practitioners'' letters contain less information about the family but more about psychiatric history than they did a decade ago. Overall, psychiatrists'' letters have not changed. Registrars, however, now include noticeably more "key items" than they did 10 years ago, but their letters remain twice the length of those written by consultants. It is suggested that letter writing skills are vital to good patient management and should be taught to postgraduate trainees in general practice and psychiatry.     

Prognostic Value of the Lymph Node Ratio in Stage III Gastric Cancer Patients Undergoing Radical Resection

Objective

The aim of this study was to investigate the prognostic value of metastatic lymph node ratio (LNR) in patients having radical resection for stage III gastric cancer.

Methods

A total of 365 patients with stage III gastric cancer who underwent radical resection between 2002 and 2008 at Tianjin Medical University Cancer Institute and Hospital were analyzed. The cut-point survival analysis was adopted to determine the appropriate cutoffs for LNR. Kaplan–Meier survival curves and log-rank tests were used for the survival analysis.

Results

By cut-point survival analysis, the LNR staging system was generated using 0.25 and 0.50 as the cutoff values. Pearson''s correlation test revealed that the LNR was related with metastatic lymph nodes but not related with total harvested lymph nodes. Cox regression analysis showed that depth of invasion and LNR were the independent predictors of survival (p<0.05). There was a significant difference in survival between each pN stages classified by the LNR staging, however no significant difference was found in survival rate between each LNR stages classified by the pN staging.

Conclusions

The LNR is an independent prognostic factor for survival in stage III gastric cancer and is superior to the pN category in TNM staging. It may be considered as a prognostic variable in future staging system.