Targeted agents for the treatment of metastatic melanoma

In the last year, the armamentarium of melanoma therapeutics has radically changed. Recent discoveries in melanoma biology and immunology have led to novel therapeutics targeting known oncogenes and immunotherapeutic antibodies. Phase III clinical trials of these agents have reported measurable and meaningful benefits to patients with metastatic disease. In this article, we review recent findings and discuss their significance in melanoma therapy. As our understanding of melanoma biology grows, this initial therapeutic success may be enhanced through the use of molecular markers to select patients, and new targeted immunotherapies in sequential or combination drug regimens

Shared mental models and intra-team psychophysiological patterns: A test of the juggling paradigm

We explored implicit coordination mechanisms underlying the conceptual notion of "shared mental models" (SMM) through physiological (i.e., breathing and heart rates) and affective-cognitive (i.e., arousal, pleasantness, attention, self-efficacy, other's efficacy) monitoring of two professional jugglers performing a real-time interactive task of increasing difficulty. There were two experimental conditions: "individual" (i.e., solo task) and "interactive" (i.e., two jugglers established a cooperative interaction by juggling sets of balls with each other). In both conditions, there were two task difficulties: “easy” and “hard”. Descriptive analyses revealed that engaging in a dyadic cooperative motor task (interactive condition) required greater physiological effort (Median Cohen’s d = 2.13) than performing a solo motor task (individual condition) of similar difficulty. Our results indicated a strong positive correlation between the jugglers’ heart rate for the easy (r = .87) and hard tasks (r = .77). The relationship between the jugglers’ breathing rate was significant for the easy task (r = .73) but non-significant for the hard task. The findings are interpreted based on research on SMM and Theory of Mind. Practitioners should advance the notion of “shared-regulation” in the context of team coordination through the use of biofeedback training

A systematic review on the relationship between self-esteem and interrogative suggestibility

Some factors, such as age, learning disability and mental health difficulties, have been identified as making police suspects more vulnerable to suggestibility and false confessions during interview. However, there has been no systematic review on the association between self-esteem and suggestibility. Seven electronic bibliographic databases and reference lists of previous literature reviews of suggestibility in children were searched. Selected studies were quality assessed using pre-defined criteria before data were extracted. Electronic searches yielded 1914 hits. Of these, 685 duplicates, 1181 irrelevant references and 39 references that did not meet the inclusion criteria were removed. Nine publications were included in the review. Significant correlations between self-esteem and suggestibility, most notably on the Yield 1 subscale of the GSS, were found but four of the nine studies found no significant correlation. The prevalent use of self-report measures and lack of clarity in defining self-esteem limit the validity of those studies

Variability in organ-specific EGFR mutational spectra in tumour epithelium and stroma may be the biological basis for differential responses to tyrosine kinase inhibitors

Organ-specific differences in epidermal growth factor receptor (EGFR) mutational spectra and frequencies were found in lung cancer and sporadic and BRCA1/2-related breast cancers. Additionally, we found a high frequency of EGFR mutations in the tumour stroma of these invasive breast carcinomas. Those organ-specific mutational spectra and potential targets in the cancer-associated stroma might influence the efficacy of TKI therapy

A Perspective on Challenges and Issues in Biomarker Development and Drug and Biomarker Codevelopment

A workshop sponsored by the National Cancer Institute and the US Food and Drug Administration addressed past lessons learned and ongoing challenges faced in biomarker development and drug and biomarker codevelopment. Participants agreed that critical decision points in the product life cycle depend on the level of understanding of the biology of the target and its interaction with the drug, the preanalytical and analytical factors affecting biomarker assay performance, and the clinical disease process. The more known about the biology and the greater the strength of association between an analytical signal and clinical result, the more efficient and less risky the development process will be. Rapid entry into clinical practice will only be achieved by using a rigorous scientific approach, including careful specimen collection and standardized and quality-controlled data collection. Early interaction with appropriate regulatory bodies will ensure studies are appropriately designed and biomarker test performance is well characterized

Porosity estimation of (Moso bamboo) by computed tomography and backscattered electron imaging

This study aims to investigate and quantify the porosity in the cross section of Phyllostachys edulis (Moso bamboo) culm wall. The porosity results are expected to be utilised in numerical study of heat and moisture transfer. Computed tomography (CT) and backscattered electron (BSE) imaging methods are utilised in this study because these two methods allow measurements of the anisotropic features of bamboo specimens. The results of these two methods can be represented as the function of the real dimension rather than the pore size distribution of the specimen. The specimens are obtained from eight different locations along the Moso bamboo culms. Both internodes and nodes specimens are measured in this study. The average porosity, standard deviation (SD) and coefficient of variation (COV) are calculated for BSE and CT results. Pearson product-moment correlation coefficient (PPMCC) is also calculated in this study to analyse the correlation between the BSE results and CT results. Typical porosity results from 400 sampling points and 10 portions average porosity are analysed in this study. The CT scanning results show similar trend with BSE results. The correlation relationship between BSE and CT results approaches moderate correlation level to strong correlation level. The average porosity of internode specimens is from 43.9 to 58.8 % by BSE measurement and from 44.9 to 63.4 % by CT measurement. The average porosity of node specimens is from 37.4 to 56.6 % by BSE measurement and from 32.1 to 62.2 % by CT measurement