Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

Pitfalls in the use of kappa when interpreting agreement between multiple raters in reliability studies

OBJECTIVE To compare different reliability coefficients (exact agreement, and variations of the kappa (generalised, Cohen's and Prevalence Adjusted and Biased Adjusted (PABAK))) for four physiotherapists conducting visual assessments of scapulae. DESIGN Inter-therapist reliability study. SETTING Research laboratory. PARTICIPANTS 30 individuals with no history of neck or shoulder pain were recruited with no obvious significant postural abnormalities. MAIN OUTCOME MEASURES Ratings of scapular posture were recorded in multiple biomechanical planes under four test conditions (at rest, and while under three isometric conditions) by four physiotherapists. RESULTS The magnitude of discrepancy between the two therapist pairs was 0.04 to 0.76 for Cohen's kappa, and 0.00 to 0.86 for PABAK. In comparison, the generalised kappa provided a score between the two paired kappa coefficients. The difference between mean generalised kappa coefficients and mean Cohen's kappa (0.02) and between mean generalised kappa and PABAK (0.02) were negligible, but the magnitude of difference between the generalised kappa and paired kappa within each plane and condition was substantial; 0.02 to 0.57 for Cohen's kappa and 0.02 to 0.63 for PABAK, respectively. CONCLUSIONS Calculating coefficients for therapist pairs alone may result in inconsistent findings. In contrast, the generalised kappa provided a coefficient close to the mean of the paired kappa coefficients. These findings support an assertion that generalised kappa may lead to a better representation of reliability between three or more raters and that reliability studies only calculating agreement between two raters should be interpreted with caution. However, generalised kappa may mask more extreme cases of agreement (or disagreement) that paired comparisons may reveal.

Global indigenous studies in the first world: some reflections and epistemological matters

Indigenous studies in First World nation states such as Australia, Canada, New Zealand, the United States of America and Hawaii, appear to have acquired the status of a discipline, although the accounts of its formation vary. Indigenous studies is formally recognised as part of university curricula in these countries and is included in inter‐disciplinary contexts and degree programs or is offered as a program and a degree in its own right. Indigenous scholarship is being published in unprecedented numbers with publishing houses competing for manuscripts. Indigenous studies journals have proliferated having emerged in the 1970s though most were, and continue to be, edited by non‐Indigenous people. In addition, Indigenous studies professional associations have been established organising research related activities as well as convening conferences to enable intellectual engagement and the formation of national and international networks. The nature and extent of this institutionalisation and the conditions of existence, though often marginalised and under resourced, may allude to the coherence of Indigenous Studies as a discipline with global reach but what remains unclear are its epistemological boundaries and the degree to which it perpetuates cultural entrapment . This paper will reflect on some of these epistemological matters.

Child sexual abuse in China : a meta-analysis of 27 studies

Objective: To examine whether Chinese studies of child sexual abuse (CSA) in the general population show lower prevalence rates than other international studies, and whether certain features of these studies may help to account for variation in estimates. Methods: A meta-analysis and meta-regression were conducted on 27 studies found in the English and Chinese language peer reviewed journals that involved general populations of students or residents, estimated CSA prior to age 18, and specified rates for males or females individually. Results: Estimates for Chinese females were lower than the international composites. For total CSA for females, the Chinese pooled estimate was 15.3% (95% CI = 12.6–18.0) based on the meta-analysis of 24 studies, lower than the international estimate (Stoltenborgh, van IJzendoorn, Euser, & Bakermans-Kranenburg, 2011) but not significantly. For contact CSA for females, the pooled estimate was 9.5% (95% CI = 7.5–11.5), based on 16 studies, significantly lower than the international prevalence. For penetrative CSA for females, the pooled estimate was 1% (95% CI = 0.7–1.3), based on 15 studies, significantly lower than the international estimate of 15.1%. Chinese men reported significantly less penetrative CSA but significantly more total CSA than international estimates; while contact CSA reported by Chinese and international males appeared to be roughly equivalent. Chinese CSA prevalence estimates were lower in studies from urban areas and non-mainland areas (Hong Kong and Taiwan), and in surveys with larger and probability samples, multiple sites, face-to-face interview method and when using less widely used instruments. Conclusions: The findings to date justify further research into possible cultural and sociological reasons for lower risk of contact and penetrative sexual abuse of girls and less penetrative abuse of boys in China. Future research should examine sociological explanations, including patterns of supervision, sexual socialization and attitudes related to male sexual prowess. Practice implications: The findings suggest that future general population studies in China should use well validated instruments, avoid face-to-face interview formats and be careful to maintain methodological standards when sampling large populations over multiple sites.

Humanities and social scientific research methods in porn studies

Porn studies researchers in the humanities have tended to use different research methods from those in social sciences. There has been surprisingly little conversation between the groups about methodology. This article presents a basic introduction to textual analysis and statistical analysis, aiming to provide for all porn studies researchers a familiarity with these two quite distinct traditions of data analysis. Comparing these two approaches, the article suggests that social science approaches are often strongly reliable – but can sacrifice validity to this end. Textual analysis is much less reliable, but has the capacity to be strongly valid. Statistical methods tend to produce a picture of human beings as groups, in terms of what they have in common, whereas humanities approaches often seek out uniqueness. Social science approaches have asked a more limited range of questions than have the humanities. The article ends with a call to mix up the kinds of research methods that are applied to various objects of study.

Screening for risk of later mental health problems : a longitudinal study

Purpose: This is one of the first studies to report that the Achenbach internalising scales were much more effective at identifying those with current comorbid depression and anxiety, rather than individual mood disorder. Introduction: The Achenbach behaviour checklists (YSR,YASR) are widely used, low cost screening tools used to assess problem behaviour. Several studies report good association between the checklists and psychiatric diagnoses; although with varying degrees of agreement. Most are cross-sectional studies involving adolescents referred to mental health services; few are in large community-based studies. This study examined the usefulness of the Achenbach internalising scales in the primary screening (both predictive and concurrent)for depression and anxiety. Methods: The sample was 2400 young adults from an Australian population-based prospective birth cohort study. The association between the empirical anxiety and depression scales were individually assessed against DSM-IV depression and anxiety diagnoses. Odds ratios and diagnostic efficiency tests report the findings. Results: Adolescents with internalising symptoms were twice (OR 2.3, 95%CI 1.7 to 3.1) as likely to be diagnosed with later DSM-IV depression. YASR internalising scale predicted DSM-IV mood disorders (depression OR = 6.9, 95% CI 5.0–9.5; anxiety OR = 5.1, 95% CI 3.8–6.7) in the previous 12 months. The internalising scales were much more effective at identifying those with comorbid depression and anxiety. Conclusions: Adolescence and early adulthood are key risk periods for the onset of anxiety and depression. This study found that young people with internalising behaviour problems were more likely to have comorbid depression and anxiety DSM-IV disorder.

Cinema studies : Women's Experimental Cinema edited by Robin Blaetz

Women’s Experimental Cinema provides lively introductions to the work of fifteen avant-garde women filmmakers, some of whom worked as early as the 1950s and many of whom are still working today. In each essay in this collection, a leading film scholar considers a single filmmaker, supplying biographical information, analyzing various influences on her work, examining the development of her corpus, and interpreting a significant number of individual films. The essays rescue the work of critically neglected but influential women filmmakers for teaching, further study, and, hopefully, restoration and preservation. Just as importantly, they enrich the understanding of feminism in cinema and expand the terrain of film history, particularly the history of the American avant-garde.

Gender studies : Intersex by Catherine Harper

Intersex is the condition whereby an individual is born with biological features that are simultaneously perceived as male and female. Ranging from the ambiguous genitalia of the true 'hermaphrodite' to the 'mildly or internally intersexed', the condition may be as common as cleft palate. Like cleft palate, it is hidden and surgically altered, but for very different reasons. Intersex draws heavily on the personal testimony of intersexed individuals, their loved ones and medical carers. The impact of early sex-assignment surgery on an individual's later life is examined within the context of ethical and clinical questions. Harper challenges the conventional and radical 'treatment' of intersexuality through non-consensual infant sex-assignment surgery. In doing so, she exposes powerful myths, taboos and constructions of gender - the perfect phallus, a bi-polar model of gender and the infallibility of medical decisions. Handling sensitive material with care, this book deepens our understanding of a condition that has itself only been medically understood in recent years.

Validation of β-actin used as endogenous control for gene expression analysis in mechanobiology studies : amendments

We write in response to the letter by Liu et al. [1] commenting on our article, ‘‘Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment’’ [2]. The study by Liu et al. demonstrates that the commonly used endogeneous reference gene (ERG), b-actin, is upregulated by mechanical loading, indicating a potential bias in the determined target gene expression when normalizing to b-actin, such as in our report on unchanged vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIF)-1a mRNA levels in mechanically loaded mesenchymal stem cells (MSCs).

French version of the Family Attitude Scale : psychometric properties and relation of attitudes to the respondent's psychiatric status

The Family Attitude Scale (FAS) is a self-report measure of critical or hostile attitudes and behaviors towards another family member, and demonstrates an ability to predict relapse in psychoses. Data are not currently available on a French version of the scale. The present study developed a French version of the FAS, using a large general population sample to test its internal structure, criterion validity and relationships with the respondents' symptoms and psychiatric diagnoses, and examined the reciprocity of FAS ratings by respondents and their partners. A total of 2072 adults from an urban population undertook a diagnostic interview and completed self-report measures, including an FAS about their partner. A subset of participants had partners who also completed the FAS. Confirmatory factor analyses revealed an excellent fit by a single-factor model, and the FAS demonstrated a strong association with dyadic adjustment. FAS scores of respondents were affected by their anxiety levels and mood, alcohol and anxiety diagnoses, and moderate reciprocity of attitudes and behaviors between the partners was seen. The French version of the FAS has similarly strong psychometric properties to the original English version. Future research should assess the ability of the French FAS to predict relapse of psychiatric disorders.

Lesson studies in Chinese kindergartens

Lesson studies are a powerful form of professional development (Doig and Groves, 2011). The processes of creating, enacting, analyzing, and refining lessons to improve teaching practices are key components of lesson studies. Lesson studies have been the primary form of professional development in Japanese classrooms for many years (Lewis, Perry and Hurd, 2009). This model is now used to improve instruction in many South-East Asian countries (White and Lim, 2008), as well as increasingly in North America (Lesson Study Research Group, 2004), and South Africa (Ono and Ferreira, 2010). In China, this form of professional development aimed at improving teaching, has also been adopted, originating from Soviet models of teacher professional development arising from influences post 1949 (China Education Yearbook, 1986). Thus, China too has a long history of improving teaching and learning through this form of school-based professional learning.