The relationship between magnetic and electrophysiological responses to complex tactile stimuli.

Background Magnetoencephalography (MEG) has become an increasingly popular technique for non-invasively characterizing neuromagnetic field changes in the brain at a high temporal resolution. To examine the reliability of the MEG signal, we compared magnetic and electrophysiological responses to complex natural stimuli from the same animals. We examined changes in neuromagnetic fields, local field potentials (LFP) and multi-unit activity (MUA) in macaque monkey primary somatosensory cortex that were induced by varying the rate of mechanical stimulation. Stimuli were applied to the fingertips with three inter-stimulus intervals (ISIs): 0.33s, 1s and 2s. Results Signal intensity was inversely related to the rate of stimulation, but to different degrees for each measurement method. The decrease in response at higher stimulation rates was significantly greater for MUA than LFP and MEG data, while no significant difference was observed between LFP and MEG recordings. Furthermore, response latency was the shortest for MUA and the longest for MEG data. Conclusion The MEG signal is an accurate representation of electrophysiological responses to complex natural stimuli. Further, the intensity and latency of the MEG signal were better correlated with the LFP than MUA data suggesting that the MEG signal reflects primarily synaptic currents rather than spiking activity. These differences in latency could be attributed to differences in the extent of spatial summation and/or differential laminar sensitivity

Six sigma, absorptive capacity and organisational learning orientation

"This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Production Research, available online: http://wwww.tandfonline.com/10.1080/00207543.2010.543175."The importance of the Six Sigma methodology in industry is growing constantly. However, there are few empirical studies that analyze the advantages of this methodology and its positive effects on organizational performance. The purpose of this paper is to extend understanding of the success of Six Sigma quality management initiatives by investigating the effects of Six Sigma teamwork and process management on absorptive capacity. It also seeks to understand the relation between absorptive capacity and organizational learning as two sources of sustainable competitive advantage. The information used comes from a larger study, the data for which were collected from a random sample of 237 European firms. Of these 237 organizations, 58 are Six Sigma organizations. Structural Equation Modelling (SEM) was used to test the hypotheses. The main findings show that Six Sigma teamwork and process management positively affect the development of absorptive capacity. A positive and significant relationship is also observed between absorptive capacity and organizational learning orientation. The findings of this study justify Six Sigma implementation in firms. This study provides us with an in-depth understanding of some structural elements that characterize the Six Sigma methodology, enabling us to provide an explanation for its success

Proteomic Analysis of Polypeptides Captured from Blood during Extracorporeal Albumin Dialysis in Patients with Cholestasis and Resistant Pruritus

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis

Do social networks affect the use of residential aged care among older Australians?

Background: Older people's social networks with family and friends can affect residential aged care use. It remains unclear if there are differences in the effects of specific (with children, other relatives, friends and confidants) and total social networks upon use of low-level residential care and nursing homes. Methods: Data were drawn from the Australian Longitudinal Study of Ageing. Six waves of data from 1477 people aged ≥ 70 collected over nine years of follow-up were used. Multinomial logistic regressions of the effects of specific and total social networks on residential care use were carried out. Propensity scores were used in the analyses to adjust for differences in participant's health, demographic and lifestyle characteristics with respect to social networks. Results Higher scores for confidant networks were protective against nursing home use (odds ratio [OR] upper versus lower tertile of confidant networks = 0.50; 95%CI 0.33–0.75). Similarly, a significant effect of upper versus lower total network tertile on nursing home use was observed (OR = 0.62; 95%CI 0.43–0.90). Evidence of an effect of children networks on nursing home use was equivocal. Nursing home use was not predicted by other relatives or friends social networks. Use of lower-level residential care was unrelated to social networks of any type. Social networks of any type did not have a significant effect upon low-level residential care use. Discussion: Better confidant and total social networks predict nursing home use in a large cohort of older Australians. Policy needs to reflect the importance of these particular relationships in considering where older people want to live in the later years of life.Lynne C Giles, Gary FV Glonek, Mary A Luszcz and Gary R Andrew

Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies

Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and protein–protein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type. We found that first neighbours have at least as high degree, betweenness centrality and clustering coefficient as cancer-related proteins themselves, indicating a previously unknown central network position. We identified a complementary strategy for mutated and differentially expressed proteins, where the affect of differentially expressed proteins having smaller network centrality is compensated with high centrality first neighbours. These first neighbours can be considered as key, so far hidden, components in cancer rewiring, with similar importance as mutated proteins. These observations strikingly suggest targeting first neighbours as a novel strategy for disrupting cancer-specific networks. Remarkably, our survey revealed 223 marketed drugs already targeting first neighbour proteins but applied mostly outside oncology, providing a potential list for drug repurposing against solid cancers. For the very central first neighbours, whose direct targeting would cause several side effects, we suggest a cancer-mimicking strategy by targeting their interactors (second neighbours of cancer-related proteins, having a central protein affecting position, similarly to the cancer-related proteins). Hence, we propose to include first neighbours to network medicine based approaches for (but not limited to) anticancer therapies