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Background: Hand hygiene compliance is generally assessed by observation of adherence to the "WHO five moments" using numbers of opportunities as the denominator. The quality of the activity is usually not monitored since there is no established methodology for the routine assessment of hand hygiene technique. The aim of this study was to objectively assess hand rub coverage of staff using a novel imaging technology and to look for patterns and trends in missed areas after the use of WHO's 6 Step technique. Methods: A hand hygiene education and assessment program targeted 5200 clinical staff over 7 days at the National University Hospital, Singapore. Participants in small groups were guided by professional trainers through 5 educational stations, which included technique-training and UV light assessment supported by digital photography of hands. Objective criteria for satisfactory hand hygiene quality were defined a priori. The database of images created during the assessment program was analyzed subsequently. Patterns of poor hand hygiene quality were identified and linked to staff demographic. Results: Despite the assessment taking place immediately after the training, only 72% of staff achieved satisfactory coverage. Failure to adequately clean the dorsal and palmar aspects of the hand occurred in 24% and 18% of the instances, respectively. Fingertips were missed by 3.5% of subjects. The analysis based on 4642 records showed that nurses performed best (77% pass), and women performed better than men (75% vs. 62%, p < 0.001). Further risk indicators have been identified regarding age and occupation. Conclusion: Ongoing education and training has a vital role in improving hand hygiene compliance and technique of clinical staff. Identification of typical sites of failure can help to develop improved training. [ABSTRACT FROM AUTHOR]

ALK (anaplastic lymphoma kinase) is an RTK (receptor tyrosine kinase) of the IRK (insulin receptor kinase) superfamily, which share an YXXXYY autophosphorylation motif within their A-loops (activation loops). A common activation and regulatory mechanism is believed to exist for members of this superfamily typified by IRK and IGF1RK (insulin-like growth factor receptor kinase-1). Chromosomal translocations involving ALK were first identified in anaplastic large-cell lymphoma, a subtype of non-Hodgkin''s lymphoma, where aberrant fusion of the ALK kinase domain with the NPM (nucleophosmin) dimerization domain results in autophosphosphorylation and ligand-independent activation. Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, which play a major role in neuroblastoma, were recently identified. To provide a structural framework for understanding these mutations and to guide structure-assisted drug discovery efforts, the X-ray crystal structure of the unphosphorylated ALK catalytic domain was determined in the apo, ADP- and staurosporine-bound forms. The structures reveal a partially inactive protein kinase conformation distinct from, and lacking, many of the negative regulatory features observed in inactive IGF1RK/IRK structures in their unphosphorylated forms. The A-loop adopts an inhibitory pose where a short proximal A-loop helix (αAL) packs against the αC helix and a novel N-terminal β-turn motif, whereas the distal portion obstructs part of the predicted peptide-binding region. The structure helps explain the reported unique peptide substrate specificity and the importance of phosphorylation of the first A-loop Tyr1278 for kinase activity and NPM–ALK transforming potential. A single amino acid difference in the ALK substrate peptide binding P−1 site (where the P-site is the phosphoacceptor site) was identified that, in conjunction with A-loop sequence variation including the RAS (Arg-Ala-Ser)-motif, rationalizes the difference in the A-loop tyrosine autophosphorylation preference between ALK and IGF1RK/IRK. Enzymatic analysis of recombinant R1275Q and F1174L ALK mutant catalytic domains confirms the enhanced activity and transforming potential of these mutants. The transforming ability of the full-length ALK mutants in soft agar colony growth assays corroborates these findings. The availability of a three-dimensional structure for ALK will facilitate future structure–function and rational drug design efforts targeting this receptor tyrosine kinase. [ABSTRACT FROM AUTHOR]