Neural Competitive Queuing of Ordinal Structure Underlies Skilled Sequential Action.

Fluent retrieval and execution of movement sequences is essential for daily activities, but the neural mechanisms underlying sequence planning remain elusive. Here participants learned finger press sequences with different orders and timings and reproduced them in a magneto-encephalography (MEG) scanner. We classified the MEG patterns for each press in the sequence and examined pattern dynamics during preparation and production. Our results demonstrate the "competitive queuing" (CQ) of upcoming action representations, extending previous computational and non-human primate recording studies to non-invasive measures in humans. In addition, we show that CQ reflects an ordinal template that generalizes across specific motor actions at each position. Finally, we demonstrate that CQ predicts participants' production accuracy and originates from parahippocampal and cerebellar sources. These results suggest that the brain learns and controls multiple sequences by flexibly combining representations of specific actions and interval timing with high-level, parallel representations of sequence position

Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates

β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as ‘transition state analogue’ inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-β-lactamases, and which could also have antimicrobial activity through inhibition of PBPs

A critical review of the research literature on Six Sigma, Lean and StuderGroup's Hardwiring Excellence in the United States: the need to demonstrate and communicate the effectiveness of transformation strategies in healthcare

<p>Abstract</p> <p>Background</p> <p>U.S. healthcare organizations are confronted with numerous and varied transformational strategies promising improvements along all dimensions of quality and performance. This article examines the peer-reviewed literature from the U.S. for evidence of effectiveness among three current popular transformational strategies: Six Sigma, Lean/Toyota Production System, and Studer's Hardwiring Excellence.</p> <p>Methods</p> <p>The English language health, healthcare management, and organizational science literature (up to December 2007) indexed in Medline, Web of Science, ABI/Inform, Cochrane Library, CINAHL, and ERIC was reviewed for studies on the aforementioned transformation strategies in healthcare settings. Articles were included if they: appeared in a peer-reviewed journal; described a specific intervention; were not classified as a pilot study; provided quantitative data; and were not review articles. Nine references on Six Sigma, nine on Lean/Toyota Production System, and one on StuderGroup meet the study's eligibility criteria.</p> <p>Results</p> <p>The reviewed studies universally concluded the implementations of these transformation strategies were successful in improving a variety of healthcare related processes and outcomes. Additionally, the existing literature reflects a wide application of these transformation strategies in terms of both settings and problems. However, despite these positive features, the vast majority had methodological limitations that might undermine the validity of the results. Common features included: weak study designs, inappropriate analyses, and failures to rule out alternative hypotheses. Furthermore, frequently absent was any attention to changes in organizational culture or substantial evidence of lasting effects from these efforts.</p> <p>Conclusion</p> <p>Despite the current popularity of these strategies, few studies meet the inclusion criteria for this review. Furthermore, each could have been improved substantially in order to ensure the validity of the conclusions, demonstrate sustainability, investigate changes in organizational culture, or even how one strategy interfaced with other concurrent and subsequent transformation efforts. While informative results can be gleaned from less rigorous studies, improved design and analysis can more effectively guide healthcare leaders who are motivated to transform their organizations and convince others of the need to employ such strategies. Demanding more exacting evaluation of projects consultants, or partnerships with health management researchers in academic settings, can support such efforts.</p

Patterns of Tobacco-Use Behavior Among Chinese Smokers with Medical Conditions

Understanding the characteristics of Chinese American smokers with medical conditions and factors associated with their tobacco-use behaviors will guide effective cessation programs. In 2008, the authors described socio-demographic profiles of Chinese smokers with medical conditions treated during the period 2002–2006, documented their tobacco-use behaviors (i.e., average daily cigarette use, nicotine dependence, and number of past-year quit attempts), and drew comparisons between subjects recruited from hospitals (IP) and ambulatory settings (OP). Compared to OP, IP were significantly older, less educated, less acculturated, and more likely to be retired. Of the two groups, IP had poorer disease profiles, smoked less (4.4 vs. 11.9 cigarettes per day), and had lower nicotine-addiction scores (5.5 vs. 6.7). There was no difference between groups in past-year quit attempts. After adjustments, the data revealed that being employed and OP was associated with higher average daily cigarette use; IP were less nicotine dependent than OP; and for both groups, years of smoking was negatively associated with past-year quit attempts. Our study suggests that, more than acculturation level, health status influences the Chinese smoker’s level of cigarette use and nicotine addiction. Given the severity of their disease profiles, IP should be aggressively targeted for intervention, as they are more likely to be light smokers and to be less nicotine dependent than OP. Future tobacco treatment studies should pay attention to health status among smokers in health-care settings in order to provide a more accurate assessment of treatment needs and of barriers to successful smoking cessation

Consistency and precision of cancer reporting in a multiwave national panel survey

Abstract Background Many epidemiological studies rely on self-reported information, the accuracy of which is critical for unbiased estimates of population health. Previously, accuracy has been analyzed by comparing self-reports to other sources, such as cancer registries. Cancer is believed to be a well-reported condition. This paper uses novel panel data to test the consistency of cancer reports for respondents with repeated self-reports. Methods Data come from 978 adults who reported having been diagnosed with cancer in at least one of four waves of the Panel Study of Income Dynamics, 1999-2005. Consistency of cancer occurrence reports and precision of timing of onset were studied as a function of individual and cancer-related characteristics using logistic and ordered logistic models. Results Almost 30% of respondents gave inconsistent cancer reports, meaning they said they never had cancer after having said they did have cancer in a previous interview; 50% reported the year of diagnosis with a discrepancy of two or more years. More recent cancers were reported with a higher consistency and timing precision; cervical cancer was reported more inaccurately than other cancer types. Demographic and socio-economic factors were only weak predictors of reporting quality. Conclusions Results suggest that retrospective reports of cancer contain significant measurement error. The errors, however, are fairly random across different social groups, meaning that the results based on the data are not systematically biased by socio-economic factors. Even for health events as salient as cancer, researchers should exercise caution about the presumed accuracy of self-reports, especially if the timing of diagnosis is an important covariate.http://deepblue.lib.umich.edu/bitstream/2027.42/112656/1/12963_2010_Article_108.pd

Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner

Objective: Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs). Methods: To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells. Results: We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane. Significance: Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma

Resveratrol Acts Not through Anti-Aggregative Pathways but Mainly via Its Scavenging Properties against Aβ and Aβ-Metal Complexes Toxicity

It has been recently suggested that resveratrol can be effective in slowing down Alzheimer's disease (AD) development. As reported in many biochemical studies, resveratrol seems to exert its neuro-protective role through inhibition of β-amyloid aggregation (Aβ), by scavenging oxidants and exerting anti-inflammatory activities. In this paper, we demonstrate that resveratrol is cytoprotective in human neuroblastoma cells exposed to Aβ and or to Aβ-metal complex. Our findings suggest that resveratrol acts not through anti-aggregative pathways but mainly via its scavenging properties