238 research outputs found

    Agent Technology in Supply Chains and Networks: An exploration of high potential future applications

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    This paper reports on an ongoing research project that\ud is aimed at evaluating how software agents can improve\ud performance of supply chains and networks. To conduct\ud this evaluation, first a framework is developed to classify\ud potential applications of software agents to supply\ud networks. The framework was used in workshop sessions\ud with logistics and information systems experts from\ud industry, software/consultancy and academia to identify\ud promising areas for agents. Based on the framework and\ud the outcome of the workshop sessions, this paper presents\ud promising application areas for the near future and\ud beyond

    Invasive monitoring of the clinical effects of high intra-abdominal pressure for insertion of the first trocar.

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    Background: To analyze the effects of transitory, high intra-abdominal pressure on clinical, hemodynamic, blood gas and metabolic parameters.

Methods: Sixty-seven laparoscopic patients were divided into groups P12 (n = 30, maximum intra-abdominal pressure of 12 mmHg) and P20 (n = 37, maximum intra-abdominal pressure of 20 mmHg). Through radial artery cannulation, mean arterial pressure (MAP) was assessed and blood gas analysis – pH, arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), bicarbonate (HCO3) and base excess (BE) – was performed. These parameters were evaluated in both groups at time point zero, before CO2 insufflation; at time point one (TP1), when intra-abdominal pressure of 12 mmHg was reached in both groups; at time point two (TP2), 5 minutes after reaching intra-abdominal pressure of 12 mmHg in group P12 and of 20 mmHg in group P20; and at time point three (TP3), 10 minutes after reaching intra-abdominal pressure of 12 mmHg in group P12 and 10 minutes after TP1 in group P20, when intra-abdominal pressure decreased from 20 mmHg to 12 mmHg. Values out of the normal range or the occurrence of atypical phenomena suggestive of organic disease indicated clinical changes.

Results: Significant variations in MAP, pH, HCO3 and BE were observed in group P20; these changes, however, were within normal limits. Clinical changes were also within normal limits, and no pathological phenomena were observed.

Conclusions: Brief, intra-abdominal hypertension for the insertion first trocar insertion causes variations in MAP, pH, HCO3 and BE without adverse effects, and it may protect from iatrogenic injury

    Why and how do political actors pursue risky welfare state reforms?

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    Why and how do political actors pursue risky welfare state reforms, in spite of the institutional mechanisms and political resistance that counteract change? This is one of the key puzzles of contemporary welfare state research, which is brought about by the absence of a complete account that identifies both the cause and causal mechanisms of risky reforms. In this article we offer a remedy for this lacuna. Prospect theory teaches us that political actors will only undertake risky reforms if they consider themselves to be in a losses domain, that is when their current situation is unacceptable. Next, we discuss the strategies that political actors use to avoid the blame associated with risky reforms. These provide the causal mechanisms linking cause and effect. The sudden outburst of risky reforms in formerly 'immovable' Italy provides an empirical illustration of our account. Copyright © 2007 Sage Publications

    The ASCIZ-DYNLL1 axis promotes 53BP1-dependent non-homologous end joining and PARP inhibitor sensitivity

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    53BP1 controls a specialized non-homologous end joining (NHEJ) pathway that is essential for adaptive immunity, yet oncogenic in BRCA1 mutant cancers. Intra-chromosomal DNA double-strand break (DSB) joining events during immunoglobulin class switch recombination (CSR) require 53BP1. However, in BRCA1 mutant cells, 53BP1 blocks homologous recombination (HR) and promotes toxic NHEJ, resulting in genomic instability. Here, we identify the protein dimerization hub—DYNLL1—as an organizer of multimeric 53BP1 complexes. DYNLL1 binding stimulates 53BP1 oligomerization, and promotes 53BP1’s recruitment to, and interaction with, DSB-associated chromatin. Consequently, DYNLL1 regulates 53BP1-dependent NHEJ: CSR is compromised upon deletion of Dynll1 or its transcriptional regulator Asciz, or by mutation of DYNLL1 binding motifs in 53BP1; furthermore, Brca1 mutant cells and tumours are rendered resistant to poly-ADP ribose polymerase (PARP) inhibitor treatments upon deletion of Dynll1 or Asciz. Thus, our results reveal a mechanism that regulates 53BP1-dependent NHEJ and the therapeutic response of BRCA1-deficient cancers

    Conserved and species-specific molecular denominators in mammalian skeletal muscle aging

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    Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species. Two downregulated pathways, the electron transport chain and oxidative phosphorylation, were common among all four species in response to aging. Quantitative PCR, biochemical analysis, mitochondrial DNA measurements, and electron microscopy revealed a conserved age-dependent decrease in mitochondrial content, and a reduction in oxidative phosphorylation complexes in monkeys and humans. Western blot analysis of key proteins in mitochondrial biogenesis discovered that (i) an imbalance toward mitochondrial fusion occurs in aged skeletal muscle and (ii) mitophagy is not overtly affected, presumably leading to the observed accumulation of abnormally large, damaged mitochondria with age. Select transcript expression analysis uncovered that the skeletal inflammatory profile differentially increases with age, but is most pronounced in humans, while increased oxidative stress (as assessed by protein carbonyl adducts and 4-hydroxynonenal) is common among all species. Expression studies also found that there is unique dysregulation of the nutrient sensing pathways among the different species with age. The identification of conserved pathways indicates common molecular mechanisms intrinsic to health and lifespan, whereas the recognition of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process

    When and How Can Endpoints Be Changed after Initiation of a Randomized Clinical Trial?

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    Contains fulltext : 52680.pdf ( ) (Open Access)OBJECTIVES: It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio). DESIGN: A randomized, placebo-controlled, double-blind clinical trial. SETTING: Radboud University Nijmegen Medical Centre, The Netherlands. PARTICIPANTS: Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals. INTERVENTION: Acclydine or placebo for 14 wk. OUTCOME MEASURES: Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis. RESULTS: There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI -4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI -201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio -0.5 (95% CI -2.8 to +1.7, p = 0.63). CONCLUSION: We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS

    How to Conduct International Geriatric Rehabilitation Research?

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    With an ageing global population and an increasing focus on aging in place, the number of people in need of geriatric rehabilitation (GR) is rapidly increasing. As current GR practice is very heterogenous, cross-country comparisons could allow us to learn from each other and optimise the effectiveness of GR. However, international GR research comes with many challenges. This article summarises the facilitators and barriers relating to the recruitment of rehabilitation centres, the inclusion of patients, and data collection, as experienced by experts in the field of international GR research. The three most important methodological recommendations for conducting cross-national collaborative research in the field of GR are (1) make use of existing (inter)national networks and social media to aid recruitment of GR centres; (2) clearly define the GR treatment, setting, and patient characteristics in the inclusion criteria; and (3) use a hierarchical study structure to communicate transparently and regularly with both national and local coordinators. International GR research would greatly benefit from the implementation of a core dataset in regular GR care. Therefore, future studies should focus on developing an international consensus regarding the outcomes and corresponding cross-culturally validated measurement instruments to be used during GR

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Characterizing Hospital Workers' Willingness to Respond to a Radiological Event

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    Terrorist use of a radiological dispersal device (RDD, or "dirty bomb"), which combines a conventional explosive device with radiological materials, is among the National Planning Scenarios of the United States government. Understanding employee willingness to respond is critical for planning experts. Previous research has demonstrated that perception of threat and efficacy is key in the assessing willingness to respond to a RDD event.An anonymous online survey was used to evaluate the willingness of hospital employees to respond to a RDD event. Agreement with a series of belief statements was assessed, following a methodology validated in previous work. The survey was available online to all 18,612 employees of the Johns Hopkins Hospital from January to March 2009.Surveys were completed by 3426 employees (18.4%), whose demographic distribution was similar to overall hospital staff. 39% of hospital workers were not willing to respond to a RDD scenario if asked but not required to do so. Only 11% more were willing if required. Workers who were hesitant to agree to work additional hours when required were 20 times less likely to report during a RDD emergency. Respondents who perceived their peers as likely to report to work in a RDD emergency were 17 times more likely to respond during a RDD event if asked. Only 27.9% of the hospital employees with a perception of low efficacy declared willingness to respond to a severe RDD event. Perception of threat had little impact on willingness to respond among hospital workers.Radiological scenarios such as RDDs are among the most dreaded emergency events yet studied. Several attitudinal indicators can help to identify hospital employees unlikely to respond. These risk-perception modifiers must then be addressed through training to enable effective hospital response to a RDD event

    Structural elements of coordination mechanisms in collaborative planning processes and their assessment through maturity models: Application to a ceramic tile company

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    Maturity is defined as a measure to evaluate the capabilities of an organization in regards to a certain discipline. The Collaborative Planning Process is a very complex process and Coordination mechanisms are especially relevant in this field to align the plans of the supply chain members. The objective of this paper is to develop a maturity model and a methodology to perform assessment for the Structural Elements of Coordination Mechanisms in the Collaborative Planning Process. Structural elements are specified in order to characterize coordination mechanisms in a collaborative planning context and they have been defined as key areas to be assessed by the maturity model. The identified structural elements are: number of decision-makers, collaboration level, interdependence relationships nature, interdepen-dence relationships type, number of coordination mechanisms, information exchanged, information processing, decision sequence characteristics and stopping criteria. Structural elements are assessed using the scheme of five levels: Initial, Repeatable, Defined, Managed and Optimized. This proposal has been applied to a ceramic tile company and the results are also reported.Cuenca, L.; Boza Garcia, A.; Alemany DĂ­az, MDM.; Trienekens, JJ. (2013). Structural elements of coordination mechanisms in collaborative planning processes and their assessment through maturity models: Application to a ceramic tile company. Computers in Industry. 64(8):898-911. doi:10.1016/j.compind.2013.06.019S89891164
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