Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients

In colorectal cancer, tumor budding at the invasive front (peritumoral budding) is an established prognostic parameter and decreased in mismatch repair-deficient tumors. In contrast, the clinical relevance of tumor budding within the tumor center (intratumoral budding) is not yet known. The aim of the study was to determine the correlation of intratumoral budding with peritumoral budding and mismatch repair status and the prognostic impact of intratumoral budding using 2 independent patient cohorts. Following pancytokeratin staining of whole-tissue sections and multiple-punch tissue microarrays, 2 independent cohorts (group 1: n = 289; group 2: n = 222) with known mismatch repair status were investigated for intratumoral budding and peritumoral budding. In group 1, intratumoral budding was strongly correlated to peritumoral budding (r = 0.64; P < .001) and less frequent in mismatch repair-deficient versus mismatch repair-proficient cases (P = .177). Sensitivity and specificity for lymph node positivity were 72.7% and 72.1%. In mismatch repair-proficient cancers, high-grade intratumoral budding was associated with right-sided location (P = .024), advanced T stage (P = .001) and N stage pN (P < .001), vascular invasion (P = .041), infiltrating tumor margin (P = .003), and shorter survival time (P = .014). In mismatch repair-deficient cancers, high intratumoral budding was linked to higher tumor grade (P = .004), vascular invasion (P = .009), infiltrating tumor margin (P = .005), and more unfavorable survival time (P = .09). These associations were confirmed in group 2. High-grade intratumoral budding was a poor prognostic factor in univariate (P < .001) and multivariable analyses (P = .019) adjusting for T stage, N stage distant metastasis, and adjuvant therapy. These preliminary results on 511 patients show that intratumoral budding is an independent prognostic factor, supporting the future investigation of intratumoral budding in larger series of both preoperative and postoperative rectal and colon cancer specimens.

Prediction of Psychosis by Mismatch Negativity

BACKGROUND: To develop risk-adapted prevention of psychosis, an accurate estimation of the individual risk of psychosis at a given time is needed. Inclusion of biological parameters into multilevel prediction models is thought to improve predictive accuracy of models on the basis of clinical variables. To this aim, mismatch negativity (MMN) was investigated in a sample clinically at high risk, comparing individuals with and without subsequent conversion to psychosis. METHODS: At baseline, an auditory oddball paradigm was used in 62 subjects meeting criteria of a late risk at-state who remained antipsychotic-naive throughout the study. Median follow-up period was 32 months (minimum of 24 months in nonconverters, n = 37). Repeated-measures analysis of covariance was employed to analyze the MMN recorded at frontocentral electrodes; additional comparisons with healthy controls (HC, n = 67) and first-episode schizophrenia patients (FES, n = 33) were performed. Predictive value was evaluated by a Cox regression model. RESULTS: Compared with nonconverters, duration MMN in converters (n = 25) showed significantly reduced amplitudes across the six frontocentral electrodes; the same applied in comparison with HC, but not FES, whereas the duration MMN in in nonconverters was comparable to HC and larger than in FES. A prognostic score was calculated based on a Cox regression model and stratified into two risk classes, which showed significantly different survival curves. CONCLUSIONS: Our findings demonstrate the duration MMN is significantly reduced in at-risk subjects converting to first-episode psychosis compared with nonconverters and may contribute not only to the prediction of conversion but also to a more individualized risk estimation and thus risk-adapted prevention.

A factor-analytic reinterpretation of the Clark-Trow "educational philosophies"

Each of four principal components analyses (n = 3,944) incorporated student self-ratings (Most accurate to Least accurate) on one of the four Clark-Trow educational philosophies: Vocational, Academic, Collegiate, Nonconformist. The analyses of these 25-variable correlation matrices yielded 2 factors differentially associated with educational philosophy: Sociability versus Independence (replacing Clark-Trow's "Identification with the College") and Liberalism versus Conservatism (replacing Clark-Trow's "Involvement with Ideas"). The Vocational philosophy was associated primarily with Conservatism, the Collegiate with Sociability, and the Nonconformist with Liberalism; the Academic was moderately associated with both Independence and Liberalism.

Higher Educational Impact on Student Objectives: Longitudinal Change in Clark-Trow "Educational Philosophies"

This study explores the impact of higher education on 3,942 arts and sciences students as measured by change in their freshman and senior ratings of four Clark-Trow "educational philosophies": vocational, academic, collegiate, and nonconformist (Clark and Trow, 1966). A repeated measures analysis of variance was applied to each of the four philosophies, controlling for sex, entering year, major, parents' educational background, scholastic aptitude, and academic motivation. As expected from Clark-Trow theory, students showed significant increases in academic and nonconformist philosophies, and decreases in vocational and collegiate philosophies. Relationships between independent variables and freshman-senior change suggested post hoc reinterpretation of the dimensions underlying the Clark-Trow "phenotypes": i. e., from "identification with the college" and "involvement with ideas" to "social interests" and "academic interests" (the latter suggested by Terenzini and Pascarella, 1977).

The Impact of Greek Affiliation on Students’ Educational Objectives: Longitudinal Change in Clark-Trow Educational Philosophies

Change in 4,119 students' freshman to senior ratings of four educational philosophies (vocational, academic, collegiate, and nonconformist) provided four measures of educational impact. Repeated measures analyses of variance compared changes in philosophy as a function of Greek affiliation, controlling for sex, historical era, major, parents' education, scholastic aptitude, and academic motivation. Small but significantly different degrees of change in the collegiate and nonconformist philosophies suggested that Greek affiliation increased social interests and inhibited some forms of intellectual interests. These small differences across all students masked the moderating effect of major. In the nonconformist philosophy, for example, the Greek × major interaction reflected substantial Greek–independent differences among humanities majors, and progressively smaller differences or reversals among social science, physical science, and engineering majors. Possible interpretations of this interaction are offered.

Knuckling Under? School Superintendents and Accountability-Based Educational Reform

The goal of this article is to explore the various ways that superintendents have responded to accountability-based educational reform efforts such as No Child Left Behind, the factors that have influenced their responses, and the implications of these responses for current and future educational leaders. With respect to the first issue, empirical data from a number of nationai studies (T. E. Glass & Franceschini, 2007; Johnson, Arumi, & Ott, 2006; Johnstone, Dilkkers, & Luedeke, 2009; Stecher et al., 2008) make clear that while there have been a variety of responses from superintendents to accountability-based reform efforts, superintendents have mostly played a supportive role. Examining the situation more fully suggests that the driving factors behind superintendent support for accountability-based educational reform are complex and are often deeply embedded within the "DNA" of the role of superintendent. This article examines the structure of this DNA by looking at the factors that influence superintendents' views of accountability-based educational reform from historical, political, and institutional perspectives. This muitifaceted approach provides new insights into the complex relationship that exists between the structure of the role of superintendent and the agency of the individuals who inhabit that role.

Educational achievement in Swiss childhood cancer survivors compared with the general population

The objective of this study was to describe educational achievements of childhood cancer survivors in Switzerland compared with the general population. In particular, the authors investigated educational problems during childhood, final educational achievement in adulthood, and its predictors.

Perfusion-diffusion mismatch in MRI to indicate endovascular treatment of cerebral vasospasm after subarachnoid haemorrhage

Endovascular treatments such as transluminal balloon angioplasty and intra-arterial nimodipine represent rescue therapy for cerebral vasospasm (CVS) after aneurysmal subarachnoid haemorrhage (SAH). Both indication and data regarding its efficacy in the prevention of cerebral infarct are, however, inconsistent. Therefore, an MR based perfusion weighted imaging/diffusion weighted imaging (PWI/DWI) mismatch was used to indicate this treatment and to characterise its effectiveness.

Educational case series: Mechanisms of drug allergy

Once administered, a drug can activate the immune system by various mechanisms and lead to a large range of clinical manifestations closely related to the type of immune reaction elicited. Administration of the drug can classically result in an immunoglobulin E (IgE)-type sensitization, but can also result in more complex activation of the immune system potentially resulting in severe syndromes, such as the drug-induced hypersensitivity syndrome (DIHS). Although there has been a major increase in our knowledge over the last years, the exact mechanisms of drug allergy are not well understood for most clinical manifestations. A complex interaction between individual characteristics, environmental factors, and the drug itself is usually responsible for adverse reactions to drugs. In this educational review series, we described three cases of drug allergy: first, a child with a typical IgE-mediated drug allergy, second, a child with a non-immediate reaction to penicillin, and in the third patient, we will discuss the drug-induced hypersensitivity syndrome, which is rare but potentially fatal. These cases are correlated to the immune mechanism potentially involved.

Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status

β-2-microglobulin (B2M) is essential for antigen presentation, yet may also possess proto-oncogenic properties.