Differences in Parent and Teacher Rating of Everyday Executive Function in Pediatric Brain Tumor Survivors

We aimed to compare executive function (EF) outcomes in pediatric brain tumor (BT) survivors compared with healthy children (HC) across multiple settings. This retrospective cross-sectional study of BT survivors and age- and gender-matched HC analyzed scale patterns of parent and teacher ratings of EF (Behavior Ratings of Executive Function; BRIEF). We also analyzed relationships between groups and raters (parent/teacher) and clinical elevations across EF domains on the BRIEF. Group differences in aspects of EF emerged from parent ratings in working memory (WM), while significant interactions from teacher ratings emerged on nearly all EF scales. Parents reported impaired cognitive/behavioral flexibility in the BT group four times more than parents of HC. Teachers rated survivors significantly more poorly as a group on the majority of EF domains, and indicated clinical impairment in cognitive/behavioral flexibility, emotional regulation, self-starting/initiation, WM, and planning and organization (P/O) four to ten times more often than the teachers of HC. Overall, teacher ratings of EF impairment in pediatric BT survivors were significantly greater than parent ratings, who reported far fewer EF problems. Possible explanations for inter-rater discrepancies include potential reporting bias/response shift in parents and/or differences in EF demands across settings.     

Biomarker Validation: Common Data Analysis Concerns

Biomarker validation, like any other confirmatory process based on statistical methodology, must discern associations that occur by chance from those reflecting true biological relationships. Validity of a biomarker is established by authenticating its correlation with clinical outcome. Validated biomarkers can lead to targeted therapy, improve clinical diagnosis, and serve as useful prognostic and predictive factors of clinical outcome. Statistical concerns such as confounding and multiplicity are common in biomarker validation studies. This article discusses four major areas of concern in the biomarker validation process and some of the proposed solutions. Because present‐day statistical packages enable the researcher to address these common concerns, the purpose of this discussion is to raise awareness of these statistical issues in the hope of improving the reproducibility of validation study findings.     

Attentional bias mediates the effect of neurostimulation on emotional vulnerability

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which has garnered recent interest in the potential treatment for emotion-based psychopathology. While accumulating evidence suggests that tDCS may attenuate emotional vulnerability, critically, little is known about underlying mechanisms of this effect. The present study sought to clarify this by examining the possibility that tDCS may affect emotional vulnerability via its capacity to modulate attentional bias towards threatening information. Fifty healthy participants were randomly assigned to receive either anodal tDCS (2 mA/min) stimulation to the left dorsolateral prefrontal cortex (DLPFC), or sham. Participants were then eye tracked during a dual-video stressor task designed to elicit emotional reactivity, while providing a concurrent in-vivo measure of attentional bias. Greater attentional bias towards threatening information was associated with greater emotional reactivity to the stressor task. Furthermore, the active tDCS group showed reduced attentional bias to threat, compared to the sham group. Importantly, attentional bias was found to statistically mediate the effect of tDCS on emotional reactivity, while no direct effect of tDCS on emotional reactivity was observed. The findings are consistent with the notion that the effect of tDCS on emotional vulnerability may be mediated by changes in attentional bias, holding implications for the application of tDCS in emotion-based psychopathology. The findings also highlight the utility of in-vivo eye tracking measures in the examination of the mechanisms associated with DLPFC neuromodulation in emotional vulnerability.     

Revealing the faults in medical journals

Medical journals hold an exalted position in medicine, but have many shortcomings. This perspective reviews some of the shortcomings of medical journals which are primarily related to inexperience, bias, and commercialism. The issues discussed include the uncertain mission of the traditional medical journal in the modern digital age, the inherent inexperience of voluntary editorial boards, the weaknesses and capricious nature of decisions made by the peer-review process, the uneven value of most journal articles, the bias in what gets submitted and published in journals, the misunderstanding about the criteria for authorship, the misunderstanding of the need for ethical review board approval of studies, the misunderstanding of the need for informed consent for research from patients and ethical review boards, the various sources of assistance to editors and authors in dealing with the many ethical issues arising in the publication process, the commercialization and manipulation of medical journals by industry, the prevalent and complex financial entanglements of authors with industry, and the imperfect impact factor, which has the potential to be abused. The perspective concludes with theorization of the role of medical journals in the future. Readers need to scrutinize data in the literature carefully and interpret the discussions and conclusions critically, as there are biases in what is published in medical journals. The editors dedicate this article to the memory of Prof. Ludwik Hirszfeld, founder of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences (Wrocław, Poland) and its two journals (Postępy Higieny i Medycyny Doświadczalnej in 1949, Archivum Immunologiae et Therapiae Experimentalis in 1953), who died fifty-five years ago.     

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

Aims/hypothesis The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association.Methods A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric.Results No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69–0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51–0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78–1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24–32% was observed among the three subgroups, although statistical significance was reached only among Asians.Conclusions/interpretation The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians.