The growing galectin network in colon cancer and clinical relevance of cytoplasmic galectin-3 reactivity

BACKGROUND/AIM Human lectins translate sugar-encoded signals of cell surface glycoconjugates into biological effects, and this is what is known for the adhesion/growth-regulatory galectins. In addition, the multifunctional members of this group can be intracellular, binding to distinct proteins. The presence of galectins and galectin reactivity were exemplarily studied in the present article. MATERIALS AND METHODS We combined immuno- and lectin histochemical monitoring in colon cancer on tissue arrays. RESULTS Intracellular presence of galectins-7 and -9 in colon cancer is detected, extending the previously known set of five expressed lectins this tumor type. The assumed significance of intracellular galectin presence, e.g. for an interplay with BCL2, β-catenin, oncogenic KRAS or synexin, is underscored by respective staining with labeled galectin-3. Statistical significance was obtained for galectin-3 staining with respect to tumor differentiation (p=0.0376), lymph node metastasis (p=0.0069) and lymphatic invasion (p=0.0156). Survival was correlated to staining, galectin-3 reactivity indicating a favorable prognosis (p=0.0183), albeit not as an independent marker. No correlation to KRAS/BRAF status was detected. CONCLUSION These results encourage further testing of labeled human galectins as probes and immunohistochemical fingerprinting instead of measuring single or few activities, in colon cancer and other tumor types.

Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data

BACKGROUND The best-known cause of intolerance to fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD) deficiency, which can result from deleterious polymorphisms in the gene encoding DPD (DPYD), including DPYD*2A and c.2846A>T. Three other variants-DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A-have been associated with DPD deficiency, but no definitive evidence for the clinical validity of these variants is available. The primary objective of this systematic review and meta-analysis was to assess the clinical validity of c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity. METHODS We did a systematic review of the literature published before Dec 17, 2014, to identify cohort studies investigating associations between DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A and severe (grade ≥3) fluoropyrimidine-associated toxicity in patients treated with fluoropyrimidines (fluorouracil, capecitabine, or tegafur-uracil as single agents, in combination with other anticancer drugs, or with radiotherapy). Individual patient data were retrieved and analysed in a multivariable analysis to obtain an adjusted relative risk (RR). Effect estimates were pooled by use of a random-effects meta-analysis. The threshold for significance was set at a p value of less than 0·0167 (Bonferroni correction). FINDINGS 7365 patients from eight studies were included in the meta-analysis. DPYD c.1679T>G was significantly associated with fluoropyrimidine-associated toxicity (adjusted RR 4·40, 95% CI 2·08-9·30, p<0·0001), as was c.1236G>A/HapB3 (1·59, 1·29-1·97, p<0·0001). The association between c.1601G>A and fluoropyrimidine-associated toxicity was not significant (adjusted RR 1·52, 95% CI 0·86-2·70, p=0·15). Analysis of individual types of toxicity showed consistent associations of c.1679T>G and c.1236G>A/HapB3 with gastrointestinal toxicity (adjusted RR 5·72, 95% CI 1·40-23·33, p=0·015; and 2·04, 1·49-2·78, p<0·0001, respectively) and haematological toxicity (adjusted RR 9·76, 95% CI 3·03-31·48, p=0·00014; and 2·07, 1·17-3·68, p=0·013, respectively), but not with hand-foot syndrome. DPYD*2A and c.2846A>T were also significantly associated with severe fluoropyrimidine-associated toxicity (adjusted RR 2·85, 95% CI 1·75-4·62, p<0·0001; and 3·02, 2·22-4·10, p<0·0001, respectively). INTERPRETATION DPYD variants c.1679T>G and c.1236G>A/HapB3 are clinically relevant predictors of fluoropyrimidine-associated toxicity. Upfront screening for these variants, in addition to the established variants DPYD*2A and c.2846A>T, is recommended to improve the safety of patients with cancer treated with fluoropyrimidines. FUNDING None.

Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis

OBJECTIVE To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.

The role and relevance of non-government aid:a case study of Kenya

How effective are non-government organisations (NG0s) in their response to Third World poverty? That is the question which this thesis examines. The thesis begins with an overview of the problems facing Third World communities, and notes the way in which people in Britain have responded through NG0s. A second part of the thesis sets out the issues on which the analysis of NGOs has been made. These are: - the ways in which NGOs analyse the process of development; - the use of 'improving nutrition' and 'promoting self-reliance' as special objectives by NG0s; and - the nature of rural change, and the implications for NGOs as agents of rural development. Kenya is taken as a case study. Firstly the political and economic structure of the country is studied, and the natures of development, nutritional problems and self-reliance in the Kenyan context are noted. The study then focusses attention onto Kitui District, an area of Kenya which at the time of the study was suffering from drought. However, it is argued that the problems of Kitui District and the constraints to change there are as much a consequence of Kenya's structural underdevelopment as of reduced rainfall. Against this background the programmes of some British NGOs in the country are examined, and it is concluded that much of their work has little relevance to the principal problems which have been identified. A final part of the thesis takes a wider look at the policies and practices of NG0s. Issues such as the choice of countries in which NGOs work, how they are represented overseas, and their educational role in Britain are considered. It is concluded that while all NGOs have a concern for the conditions in which the poorest communities of the Third World live, many NGOs take a quite narrow view of development problems, giving only little recognition to the international and intranational political and economic systems which contribute to Third World poverty.

From depressive symptoms to depressive disorders:the relevance of thresholds

BACKGROUND: Nosological boundaries for depressive disorders as well as the prevalence and impact of 'subsyndromal' depression remain unclear. AIMS: To examine the impact of subsyndromal depressive disorders on health status and to assess if depressive disorders lie on a continuum of severity. METHOD: The sample was composed of randomly selected respondents from the general population in 68 countries from across the world participating in the World Health Organization's World Health Survey. RESULTS: The pattern of risk factors for depressive disorders was consistent across all types of depression (subsyndromal, brief depressive episode and depressive episode): odds ratios for females ranged between 1.49 and 1.80, and for the unemployed from 1.19 to 1.25. All types of depression produced a significant decrement in health status compared with no depression after controlling for demographic variables, income and country. CONCLUSIONS: Subthreshold depressive disorders occur commonly all across the world and are associated with the same risk factors everywhere. They produce significant decrements in health and do not qualitatively differ from full-blown episodes of depression as currently defined, and lie on a continuum with more severe forms of depressive episodes but are distinct from normal mood changes.

Working at the interface : the descriptive relevance of Grunig and Hunt’s theories to public relations practices in south east Queensland schools

This article examines the relevance of James Grunig and Todd Hunt’s (1984) theories to public relations practitioners’ roles in south east Queensland schools. It focuses in particular on the two-way symmetric model in this context. The geographical boundaries of the research mean that this article is intended primarily as an exploratory, descriptive analysis of a specific area rather than an exhaustive treatise on the general topic of public relations in Australian schools. However, it is hoped that it will prove useful in identifying bases for further study and discussion.

Compliance with international financial reporting standards (IFRS) and the value relevance of accounting information in emerging stock markets : evidence from Kuwait

Since the 1960s, the value relevance of accounting information has been an important topic in accounting research. The value relevance research provides evidence as to whether accounting numbers relate to corporate value in a predicted manner (Beaver, 2002). Such research is not only important for investors but also provides useful insights into accounting reporting effectiveness for standard setters and other users. Both the quality of accounting standards used and the effectiveness associated with implementing these standards are fundamental prerequisites for high value relevance (Hellstrom, 2006). However, while the literature comprehensively documents the value relevance of accounting information in developed markets, little attention has been given to emerging markets where the quality of accounting standards and their enforcement are questionable. Moreover, there is currently no known research that explores the association between level of compliance with International Financial Reporting Standards (IFRS) and the value relevance of accounting information. Motivated by the lack of research on the value relevance of accounting information in emerging markets and the unique institutional setting in Kuwait, this study has three objectives. First, it investigates the extent of compliance with IFRS with respect to firms listed on the Kuwait Stock Exchange (KSE). Second, it examines the value relevance of accounting information produced by KSE-listed firms over the 1995 to 2006 period. The third objective links the first two and explores the association between the level of compliance with IFRS and the value relevance of accounting information to market participants. Since it is among the first countries to adopt IFRS, Kuwait provides an ideal setting in which to explore these objectives. In addition, the Kuwaiti accounting environment provides an interesting regulatory context in which each KSE-listed firm is required to appoint at least two external auditors from separate auditing firms. Based on the research objectives, five research questions (RQs) are addressed. RQ1 and RQ2 aim to determine the extent to which KSE-listed firms comply with IFRS and factors contributing to variations in compliance levels. These factors include firm attributes (firm age, leverage, size, profitability, liquidity), the number of brand name (Big-4) auditing firms auditing a firm’s financial statements, and industry categorization. RQ3 and RQ4 address the value relevance of IFRS-based financial statements to investors. RQ5 addresses whether the level of compliance with IFRS contributes to the value relevance of accounting information provided to investors. Based on the potential improvement in value relevance from adopting and complying with IFRS, it is predicted that the higher the level of compliance with IFRS, the greater the value relevance of book values and earnings. The research design of the study consists of two parts. First, in accordance with prior disclosure research, the level of compliance with mandatory IFRS is examined using a disclosure index. Second, the value relevance of financial statement information, specifically, earnings and book value, is examined empirically using two valuation models: price and returns models. The combined empirical evidence that results from the application of both models provides comprehensive insights into value relevance of accounting information in an emerging market setting. Consistent with expectations, the results show the average level of compliance with IFRS mandatory disclosures for all KSE-listed firms in 2006 was 72.6 percent; thus, indicating KSE-listed firms generally did not fully comply with all requirements. Significant variations in the extent of compliance are observed among firms and across accounting standards. As predicted, older, highly leveraged, larger, and profitable KSE-listed firms are more likely to comply with IFRS required disclosures. Interestingly, significant differences in the level of compliance are observed across the three possible auditor combinations of two Big-4, two non-Big 4, and mixed audit firm types. The results for the price and returns models provide evidence that earnings and book values are significant factors in the valuation of KSE-listed firms during the 1995 to 2006 period. However, the results show that the value relevance of earnings and book values decreased significantly during that period, suggesting that investors rely less on financial statements, possibly due to the increase in the available non-financial statement sources. Notwithstanding this decline, a significant association is observed between the level of compliance with IFRS and the value relevance of earnings and book value to KSE investors. The findings make several important contributions. First, they raise concerns about the effectiveness of the regulatory body that oversees compliance with IFRS in Kuwait. Second, they challenge the effectiveness of the two-auditor requirement in promoting compliance with regulations as well as the associated cost-benefit of this requirement for firms. Third, they provide the first known empirical evidence linking the level of IFRS compliance with the value relevance of financial statement information. Finally, the findings are relevant for standard setters and for their current review of KSE regulations. In particular, they highlight the importance of establishing and maintaining adequate monitoring and enforcement mechanisms to ensure compliance with accounting standards. In addition, the finding that stricter compliance with IFRS improves the value relevance of accounting information highlights the importance of full compliance with IFRS and not just mere adoption.

Students' perceptions of the relevance of mathematics in engineering

In this paper, we report on the findings of an exploratory study into the experience of students as they learn first year engineering mathematics. Here we define engineering as the application of mathematics and sciences to the building and design of projects for the use of society (Kirschenman and Brenner 2010)d. Qualitative and quantitative data on students' views of the relevance of their mathematics study to their engineering studies and future careers in engineering was collected. The students described using a range of mathematics techniques (mathematics skills developed, mathematics concepts applied to engineering and skills developed relevant for engineering) for various usages (as a subject of study, a tool for other subjects or a tool for real world problems). We found a number of themes relating to the design of mathematics engineering curriculum emerged from the data. These included the relevance of mathematics within different engineering majors, the relevance of mathematics to future studies, the relevance of learning mathematical rigour, and the effectiveness of problem solving tasks in conveying the relevance of mathematics more effectively than other forms of assessment. We make recommendations for the design of engineering mathematics curriculum based on our findings.