293 research outputs found

    The Leader’s Mind Matters: The Effect of Mindful Leadership Development Programs on Leadership Effectiveness, Mindfulness, and Well-Being Among Global Manufacturing Leaders

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    The purpose of this quasi-experimental quantitative study was to examine the effects of mindful leadership development programs and mindfulness practices on wellbeing, dispositional mindfulness, and leadership effectiveness among 102 global manufacturing leaders facing volatile, uncertain, complex, and ambiguous (VUCA) business environments. Organizations worldwide report challenges to develop leaders to lead effectively and maintain well-being in VUCA environments. Evidence points to the benefits of mindfulness to reduce stress and anxiety, in addition to providing behavioral and cognitive improvements to support leadership effectiveness. Although a few global organizations are offering mindful leadership development programs, there is a gap between industry practices and scholarly research. The results of this study suggest leaders who completed one mindful leadership development program reported greater well-being and received higher annual leadership effectiveness performance appraisal scores (PAS). Leaders who engaged in consistent mindfulness practices also reported higher levels of leadership effectiveness (PAS) as compared to leaders without a mindfulness practice. Implications exist for the bodies of knowledge concerning well-being and leadership effectiveness in VUCA environments, and leadership development programs. Recommendations were provided for future research, culture and strategy, professional practice, and executive leadership. This is the first study (to date) to investigate the effects of mindful leadership development programs for global manufacturing leaders facing VUCA conditions

    The Alternate Arm Converter: A New Hybrid Multilevel Converter With DC-Fault Blocking Capability

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    This paper explains the working principles, supported by simulation results, of a new converter topology intended for HVDC applications, called the alternate arm converter (AAC). It is a hybrid between the modular multilevel converter, because of the presence of H-bridge cells, and the two-level converter, in the form of director switches in each arm. This converter is able to generate a multilevel ac voltage and since its stacks of cells consist of H-bridge cells instead of half-bridge cells, they are able to generate higher ac voltage than the dc terminal voltage. This allows the AAC to operate at an optimal point, called the “sweet spot,” where the ac and dc energy flows equal. The director switches in the AAC are responsible for alternating the conduction period of each arm, leading to a significant reduction in the number of cells in the stacks. Furthermore, the AAC can keep control of the current in the phase reactor even in case of a dc-side fault and support the ac grid, through a STATCOM mode. Simulation results and loss calculations are presented in this paper in order to support the claimed features of the AAC

    LD Motif Recognition by Talin: Structure of the Talin-DLC1 Complex

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    Cell migration requires coordination between integrin-mediated cell adhesion to the extracellular matrix and force applied to adhesion sites. Talin plays a key role in coupling integrin receptors to the actomyosin contractile machinery, while deleted in liver cancer 1 (DLC1) is a Rho GAP that binds talin and regulates Rho, and therefore actomyosin contractility. We show that the LD motif of DLC1 forms a helix that binds to the four-helix bundle of the talin R8 domain in a canonical triple-helix arrangement. We demonstrate that the same R8 surface interacts with the paxillin LD1 and LD2 motifs. We identify key charged residues that stabilize the R8 interactions with LD motifs and demonstrate their importance in vitro and in cells. Our results suggest a network of competitive interactions in adhesion complexes that involve LD motifs, and identify mutations that can be used to analyze the biological roles of specific protein-protein interactions in cell migration

    Carboxyhaemoglobin levels and their determinants in older British men

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    Background: Although there has been concern about the levels of carbon monoxide exposure, particularly among older people, little is known about COHb levels and their determinants in the general population. We examined these issues in a study of older British men.Methods: Cross-sectional study of 4252 men aged 60-79 years selected from one socially representative general practice in each of 24 British towns and who attended for examination between 1998 and 2000. Blood samples were measured for COHb and information on social, household and individual factors assessed by questionnaire. Analyses were based on 3603 men measured in or close to (< 10 miles) their place of residence.Results: The COHb distribution was positively skewed. Geometric mean COHb level was 0.46% and the median 0.50%; 9.2% of men had a COHb level of 2.5% or more and 0.1% of subjects had a level of 7.5% or more. Factors which were independently related to mean COHb level included season (highest in autumn and winter), region (highest in Northern England), gas cooking (slight increase) and central heating (slight decrease) and active smoking, the strongest determinant. Mean COHb levels were more than ten times greater in men smoking more than 20 cigarettes a day (3.29%) compared with non-smokers (0.32%); almost all subjects with COHb levels of 2.5% and above were smokers (93%). Pipe and cigar smoking was associated with more modest increases in COHb level. Passive cigarette smoking exposure had no independent association with COHb after adjustment for other factors. Active smoking accounted for 41% of variance in COHb level and all factors together for 47%.Conclusion: An appreciable proportion of men have COHb levels of 2.5% or more at which symptomatic effects may occur, though very high levels are uncommon. The results confirm that smoking (particularly cigarette smoking) is the dominant influence on COHb levels

    EVIDENCE BASED PUBLIC HEALTH POLICY AND PRACTICE Explaining the recent decrease in coronary heart disease mortality rates in Ireland, 1985-2000

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    Study objectives: To examine the proportion of the recent decline in coronary heart disease (CHD) deaths in Ireland attributable to (a) &apos;&apos;evidence based&apos;&apos; medical and surgical treatments, and (b) changes in major cardiovascular risk factors. Design setting: IMPACT, a previously validated model, was used to combine and analyse data on the use and effectiveness of specific cardiology treatments and risk factor trends, stratified by age and sex. The main data sources were published trials and meta-analyses, official statistics, clinical audits, and observational studies. Results: Between 1985 and 2000, CHD mortality rates in Ireland fell by 47% in those aged 25-84. Some 43.6% of the observed decrease in mortality was attributed to treatment effects and 48.1% to favourable population risk factor trends; specifically declining smoking prevalence (25.6%), mean cholesterol concentrations (30.2%), and blood pressure levels (6.0%), but offset by increases in adverse population trends related to obesity, diabetes, and inactivity (213.8%). Conclusions: The results emphasise the importance of a comprehensive strategy that maximises population coverage of effective treatments, and that actively promotes primary prevention, particularly tobacco control and a cardioprotective diet

    NMR assignment of the C-terminal actin-binding domain of talin.

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    Talin is a large dimeric 270 kDa adapter protein which binds the cytoplasmic face of a subset of integrin beta-subunits and couples them to the actin cytoskeleton. Here we report the near complete 15N, 13C and 1H chemical shift assignments for the C-terminal actin-binding domain

    Evidence that talin alternative splice variants from Ciona intestinalis have different roles in cell adhesion

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    BACKGROUND: Talins are large, modular cytoskeletal proteins found in animals and amoebozoans such as Dictyostelium discoideum. Since the identification of a second talin gene in vertebrates, it has become increasingly clear that vertebrate Talin1 and Talin2 have non-redundant roles as essential links between integrins and the actin cytoskeleton in distinct plasma membrane-associated adhesion complexes. The conserved C-terminal I/LWEQ module is important for talin function. This structural element mediates the interaction of talins with F-actin. The I/LWEQ module also targets mammalian Talin1 to focal adhesion complexes, which are dynamic multicomponent assemblies required for cell adhesion and cell motility. Although Talin1 is essential for focal adhesion function, Talin2 is not targeted to focal adhesions. The nonvertebrate chordate Ciona intestinalis has only one talin gene, but alternative splicing of the talin mRNA produces two proteins with different C-terminal I/LWEQ modules. Thus, C. intestinalis contains two talins, Talin-a and Talin-b, with potentially different activities, despite having only one talin gene. RESULTS: We show here that, based on their distribution in cDNA libraries, Talin-a and Talin-b are differentially expressed during C. intestinalis development. The I/LWEQ modules of the two proteins also have different affinities for F-actin. Consistent with the hypothesis that Talin-a and Talin-b have different roles in cell adhesion, the distinct I/LWEQ modules of Talin-a and Talin-b possess different subcellular targeting determinants. The I/LWEQ module of Talin-a is targeted to focal adhesions, where it most likely serves as the link between integrin and the actin cytoskeleton. The Talin-b I/LWEQ module is not targeted to focal adhesions, but instead preferentially labels F-actin stress fibers. These different properties of C. intestinalis the Talin-a and Talin-b I/LWEQ modules mimic the differences between mammalian Talin1 and Talin2. CONCLUSION: Vertebrates and D. discoideum contain two talin genes that encode proteins with different functions. The urochordate C. intestinalis has a single talin gene but produces two separate talins by alternative splicing that vary in a domain crucial for talin function. This suggests that multicellular organisms require multiple talins as components of adhesion complexes. In C. intestinalis, alternative splicing, rather than gene duplication followed by neo-functionalization, accounts for the presence of multiple talins with different properties. Given that C. intestinalis is an excellent model system for chordate biology, the study of Talin-a and Talin-b will lead to a deeper understanding of cell adhesion in the chordate lineage and how talin functions have been parceled out to multiple proteins during metazoan evolution

    An investigation into the age and origin of Suranga in the foothills of the Western Ghats of India

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    This document is the Accepted Manuscript version. The final publication is available at Springer via: https://doi.org/10.1007/s12685-015-0125-yThis paper presents the evidence for determining the age and origin of suranga irrigation found mainly in southern Karnataka and northern Kerala in the foothills of the Western Ghats of south India. It draws on on-going research that has attempted to use an interdisciplinary approach to date the system using Indian Archives, British and Portuguese colonial archives, etymology, oral testimony archaeology, phenology and palaeo dating techniques. The results from this study put the origins of the system at around 1900–1940 CE. These results are compared with the current academic discourse that supports the view that the system originates from ancient Persia and qanat technology, because of the long established trade links with Persia and the Arabian Peninsula in the Malabar region. We argue that a new ‘origin discourse’ should be framed around these much more recent dates. The methodological constraints behind both theories are discussed throughout to enable the reader to appreciate the limitations of both arguments.Peer reviewedFinal Accepted Versio

    Structural and biophysical properties of the integrin-associated cytoskeletal protein talin

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    Talin is a large cytoskeletal protein (2541 amino acid residues) which plays a key role in integrin-mediated events that are crucial for cell adhesion, migration, proliferation and survival. This review summarises recent work on the structure of talin and on some of the structurally better defined interactions with other proteins. The N-terminal talin head (approx. 50 kDa) consists of an atypical FERM domain linked to a long flexible rod (approx. 220 kDa) made up of a series of amphipathic helical bundle domains. The F3 FERM subdomain in the head binds the cytoplasmic tail of integrins, but this interaction can be inhibited by an interaction of F3 with a helical bundle in the talin rod, the so-called “autoinhibited form” of the molecule. The talin rod contains a second integrin-binding site, at least two actin-binding sites and a large number of binding sites for vinculin, which is important in reinforcing the initial integrin–actin link mediated by talin. The vinculin binding sites are defined by hydrophobic residues buried within helical bundles, and these must unfold to allow vinculin binding. Recent experiments suggest that this unfolding may be mediated by mechanical force exerted on the talin molecule by actomyosin contraction

    Using haloperidol as an anti-emetic in palliative care: informing practice through evidence from cancer treatment and post-operative contexts

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    YesNausea and vomiting are common symptoms in palliative care. Haloperidol is often used as an antiemetic in this context, although direct evidence supporting this practice is limited. To evaluate the efficacy and clinical use of haloperidol as an antiemetic in nonpalliative care contexts to inform practice, the authors conducted a rapid review of (i) published evidence to supplement existing systematic reviews, and (ii) practical aspects affecting the use of haloperidol including formulations and doses that are commonly available internationally. In nausea and vomiting related to cancer treatment, haloperidol was superior to control in two small studies. In postoperative nausea and vomiting (PONV), two randomized controlledtrials found treatment with haloperidol comparable to ondansetron. In palliative care, an observational study found a complete response rate of 24% with haloperidol (one in four patients) which would be consistent with a number needed to treat (NNT) of 3 to 5 derived from PONV. There remains insufficient direct evidence to definitively support the use of haloperidol for the management of nausea and vomiting in palliative care. However, generalizing evidence from other clinical contexts may have some validity
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