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Background The purpose of this review was to understand whether adding antimicrobial agents to hand hygiene products could increase the health benefits of handwashing with plain soap (HWWS) in low-income settings. Methods A review of experimental studies comparing the effects of HWWS with antimicrobial soap and waterless hand sanitizer on health and hand contamination in naturalistic conditions was conducted. In addition, an analysis was completed of the evidence from laboratory studies examining the factors that may affect the impact of antimicrobial soap, taking into account the conditions in low-income settings. Results The review found no evidence for a superior effect of antimicrobial products compared with HWWS on disease incidence and limited evidence for an effect on hand contamination under naturalistic conditions. An analysis of the effectiveness of antimicrobial soap in laboratory settings suggested that it was only more effective than HWWS when handwashing frequency, duration, and product concentrations were above levels that could be expected in low-income settings. Conclusions The limited available evidence suggests that under naturalistic conditions, antimicrobial products are no more effective than HWWS in removing pathogens from hands. Without significant improvement in efficacy, antimicrobial products are unlikely to produce greater health gains than HWWS in low-income settings.

Introduction Diffuse gliomas are highly infiltrative tumours of the central nervous system that lack effective treatment options and suffer from poor survival. We and others have used DNA methylation and gene expression profiling to stratify these tumours into clinically relevant subtypes. Nevertheless, diffuse gliomas are notoriously heterogeneous and a single biopsy is unlikely to reflect all tumour cell populations. Advanced sampling schemes guided by imaging are needed for accurate delineation of heterogeneity. Material and methods We obtained 74 stereotactic image-guided biopsies in eight patients with glioma prior to craniotomy in addition to 102 multi-sector glioma samples from 25 patients from outside sources. Patients underwent extensive imaging including standard magnetic resonance imaging and various advanced modalities. For each patient, multiple biopsies were taken from the tumour core, tumour margin and outside of visible imaging abnormalities and each sample was histologically assessed by two board-certified pathologists. We performed methylation profiling on all samples. We used supervised machine learning to determine methylation subtype composition and predict transcriptional subtypes in each sample. Genome wide DNA copy number was inferred. Results and discussions Principal component analysis of DNA methylation separated samples based on IDH status and tumour cell content. Tumour signal could be detected in samples far outside tumour margins on standard MRI, despite demonstrating lower tumour purity and inconclusive tumour subtypes. Samples taken from inside imaging abnormalities demonstrated concordant methylation subtypes, suggesting that this classifier is reliable and not subject to heterogeneity due to microenvironment cell populations as often the case with gene expression subtyping. Despite uniformity in classification, IDH mutant tumours demonstrated a higher degree of epigenetic heterogeneity compared to wild-type tumours, reflecting hypermethylation established by IDH oncometabolites. Although still imperfect, advanced imaging substantially improved tumour delineation. While samples from inside imaging abnormalities are optimal for diagnostic use, tumour cells infiltrate well beyond these boundaries and treatment of these regions should be considered when safe and feasible. Conclusion These data show methylation profiling is stable across multiple biopsies and could serve as a powerful diagnostic biomarker. Moreover, advanced imaging can more accurately delineate tumour margins and could help direct treatment.

Progressive tumor growth depends on angiogenesis to sustain metabolic needs of tumor cells, thus providing a potential target for cancer therapy. Malignant gliomas have retained their dismal prognosis despite aggressive multimodal conventional therapeutic approaches, illustrating the need for novel therapeutic strategies. Gliomas are a suitable tumor type for probing angiogenesis inhibition as their proliferation is characterized by a prominent proliferative vascular component. In the present review, we discuss the current status and future directions of angiogenesis inhibition in gliomas. We focus on recently developed approaches inducing an antiangiogenic response such as targeted gene delivery, protein tyrosine kinase inhibitors and encapsulated producer cells. Although several of these modalities have shown promising results on their own, the true potential of these novel approaches lies in their combined use with radiotherapy or 'metronomically scheduled' chemotherapy. A combined approach potentially counteracts the selective pressure on hypoxia-resistant malignant tumor cells, circumvents endothelial resistance induced by local cytoprotective responses and enhances the delivery of cytotoxic agents by normalizing vascular physiology. Surrogate markers of angiogenesis currently under study may provide accurate assessment of response in individual patients. Future research on endothelial markers expressed on tumor-associated vasculature as well as endothelial responses to cytotoxic treatment will provide new avenues for molecularly targeted therapy in malignant gliomas. (C) 2004 Elsevier B.V. All rights reserved

Furan o-aminonitriles may be utilized as precursors in the synthesis of flavone-8-carboxylic acids. Some results from in vivo evaluation against P388 leukemia, colon carcinoma 38, and B16 melanoma models suggest that selected examples of the acids are potentially as effective as the antitumor compound, flavone acetic acid. The flavone-8-carboxylic acids did not exhibit significant activity against an in vitro HIV screen or an in vitro antitumor screen consisting of a cell panel of 60 lines.

The relation of stress scores with cortisol and sAA under the curve (AUC) values from the injured children was examined using Spearman correlations controlling for age. Cortisol AUC was not related to stress scores for either group. The relation of sAA AUC differed significantly between the TBI and EI groups for the total, avoidance, and arousal scores (ps < .03). Higher stress scores were significantly associated with lower sAA AUC levels for TBI andwith higher AUC for participants with EI. TBIwas associatedwithelevated sAAaswell as an increased cortisol stress response in younger participants. Additional research is needed toexaminedivergent relationsof sAAwith stress symptoms in youth with TBI and EI.

We thank David R Cox for developing a suitable non-parametric method for estimation of the case fatality rate. ACG and NMF receive fellowship support from The Royal Society. SR and NMF receive research funding from the Howard Hughes Medical Institute, CF, LJA-R, and NMF from the Medical Research Council, and RMA from the Wellcome Trust. We thank Tom Johnston for Geographic Information System assistance. We thank all our colleagues in the Department of Health and the Hospital Authority for their work in data collection and processing, and pay tribute to all the front-line health workers who are caring for patients with SARS. ARTICLES