2,010 research outputs found

    Business-friendly contracting : how simplification and visualization can help bring it to practice

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    One thesis of this book is that the legal function within businesses will shift from a paradigm of security to one of opportunity. This chapter embraces that likelihood in the context of business contracting, where voices calling for a major shift are starting to surface. It explores how contracts can be used to reach better outcomes and relationships, not just safer ones. It introduces the concept of business-friendly contracting, highlighting the need for contracts to be seen as business tools rather than exclusively as legal tools, and working as business enablers rather than obstacles. By changing the design of contracts and the ways in which those contracts are communicated—through simplification and visualization, for example—legal and business operations can be better integrated. Contracts can then be more useful to business, and contract provisions can actually become more secure by becoming easier to negotiate and implement.fi=vertaisarvioitu|en=peerReviewed

    A study of blood contamination of Siqveland matrix bands

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    AIMS To use a sensitive forensic test to measure blood contamination of used Siqveland matrix bands following routine cleaning and sterilisation procedures in general dental practice. MATERIALS AND METHODS: Sixteen general dental practices in the West of Scotland participated. Details of instrument cleaning procedures were recorded for each practice. A total of 133 Siqveland matrix bands were recovered following cleaning and sterilisation and were examined for residual blood contamination by the Kastle-Meyer test, a well-recognised forensic technique. RESULTS: Ultrasonic baths were used for the cleaning of 62 (47%) bands and retainers and the remainder (53%) were hand scrubbed prior to autoclaving. Overall, 21% of the matrix bands and 19% of the retainers gave a positive Kastle-Meyer test, indicative of residual blood contamination, following cleaning and sterilisation. In relation to cleaning method, 34% of hand-scrubbed bands and 32% of hand-scrubbed retainers were positive for residual blood by the Kastle-Meyer test compared with 6% and 3% respectively of ultrasonically cleaned bands and retainers (P less than 0.001). CONCLUSIONS: If Siqveland matrix bands are re-processed in the assembled state, then adequate pre-sterilisation cleaning cannot be achieved reliably. Ultrasonic baths are significantly more effective than hand cleaning for these items of equipment

    Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

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    Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis

    A Modeling Framework to Assess Strategies Alignment based on Collaborative Network Emotions

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    [DE] The Collaborative Networks (CN) discipline has been largely studied in last decades, addressing different problems and proposing solutions for the robust establishment of collaborative processes, within the enterprises willing to collaborate. The main aim of CN research is, therefore, to generate approaches that enable creating effective relationships in the long term, to achieve stable and agile alliances. The concept of alignment among the CN partners has been considered since the beginning of CN research. Nevertheless, novel perspectives of study in CN, such as the consideration of collaborative emotional states, within the CN, have been introduced in recent years. This paper connects the research area of strategies alignment and the CN emotion models. Accordingly, a modelling framework to assess strategies alignment considering the emotional environment within the CN is proposed. The modelling framework allows representing how the enterprises emotions affect in the selection and alignment of formulated enterprises¿ strategiesAndres, B.; Ferrada, F.; Poler, R.; Camarinha-Matos, L. (2018). A Modeling Framework to Assess Strategies Alignment based on Collaborative Network Emotions. IFIP Advances in Information and Communication Technology. 534:349-361. https://doi.org/10.1007/978-3-319-99127-6_30S349361534Camarinha-Matos, L.M.: Collaborative networks in industry and the role of PRO-VE. Int. J. Prod. Manag. Eng. 2(2), 53–57 (2014)Andres, B., Poler, R.: Models, guidelines and tools for the integration of collaborative processes in non-hierarchical manufacturing networks: a review. Int. J. Comput. Integr. Manuf. 2(29), 166–201 (2016)Bititci, U., Martinez, V., Albores, P., Parung, J.: Creating and managing value in collaborative networks. Int. J. Phys. Distrib. Logist. Manag. 34(3/4), 251–268 (2004)Carbo, B.: Align the organization for improved supply chain performance. ASCET Proj. 2, 244–447 (2002)Macedo, P., Camarinha-Matos, L.: Value systems alignment analysis in collaborative networked organizations management. Appl. Sci. 7(12), 123 (2017)Andres, B., Poler, R.: A decision support system for the collaborative selection of strategies in enterprise networks. Decis. Support Syst. 91, 113–123 (2016)Andres, B., Macedo, P., Camarinha-Matos, L.M., Poler, R.: Achieving coherence between strategies and value systems in collaborative networks. In: Camarinha-Matos, L.M., Afsarmanesh, H. (eds.) PRO-VE 2014. IFIP AICT, vol. 434, pp. 261–272. Springer, Heidelberg (2014). https://doi.org/10.1007/978-3-662-44745-1_26Ferrada, F., Camarinha-Matos, L.M.: A system dynamics and agent-based approach to model emotions in collaborative networks. In: Camarinha-Matos, L.M., Parreira-Rocha, M., Ramezani, J. (eds.) DoCEIS 2017. IFIP AICT, vol. 499, pp. 29–43. 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Rev. 3, 281–296 (2000)Lyneisa, J.M.: System dynamics for market forecasting and structural analysis. Syst. Dyn. Rev. 16(1), 3–25 (2000)Borshchev, A., Filippov, A.: From system dynamics and discrete event to practical agent based modeling: reasons, techniques, tools. In: The 22nd International Conference of the System Dynamics Society (2004)Ferrada, F.: C-EMO: A Modeling Framework for Collaborative Network Emotions Doctoral dissertation, Nova University of Lisbon, Portugal (2017). https://run.unl.pt/handle/10362/26857Scherer, K.R.: Emotions are emergent processes: they require a dynamic computational architecture. Rev. Philos. Trans. R. Soc. Biol. Sci. 364(1535), 3459–3474 (2009

    The clinical features of the piriformis syndrome: a systematic review

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    Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

    Limits to the Rate of Adaptive Substitution in Sexual Populations

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    In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, , that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is , where is the population size, is the rate of beneficial mutations per genome, and is their mean selective advantage. Heritable variance in log fitness due to unlinked loci reduces by under polygamy and under monogamy. With a linear genetic map of length Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on , , , and only through the baseline density: . Under the approximation that the interference due to different sweeps adds up, we show that , implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for ; for higher , the rate of adaptation grows above , but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common—diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection

    Corrigendum to: Cohort profile: Extended Cohort for E-health, Environment and DNA (EXCEED)

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    This is a correction to: International Journal of Epidemiology, Volume 48, Issue 3, June 2019, Pages 678–679j, https://doi.org/10.1093/ije/dyz07

    Improving the Prognostic Ability through Better Use of Standard Clinical Data - The Nottingham Prognostic Index as an Example

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    Background Prognostic factors and prognostic models play a key role in medical research and patient management. The Nottingham Prognostic Index (NPI) is a well-established prognostic classification scheme for patients with breast cancer. In a very simple way, it combines the information from tumor size, lymph node stage and tumor grade. For the resulting index cutpoints are proposed to classify it into three to six groups with different prognosis. As not all prognostic information from the three and other standard factors is used, we will consider improvement of the prognostic ability using suitable analysis approaches. Methods and Findings Reanalyzing overall survival data of 1560 patients from a clinical database by using multivariable fractional polynomials and further modern statistical methods we illustrate suitable multivariable modelling and methods to derive and assess the prognostic ability of an index. Using a REMARK type profile we summarize relevant steps of the analysis. Adding the information from hormonal receptor status and using the full information from the three NPI components, specifically concerning the number of positive lymph nodes, an extended NPI with improved prognostic ability is derived. Conclusions The prognostic ability of even one of the best established prognostic index in medicine can be improved by using suitable statistical methodology to extract the full information from standard clinical data. This extended version of the NPI can serve as a benchmark to assess the added value of new information, ranging from a new single clinical marker to a derived index from omics data. An established benchmark would also help to harmonize the statistical analyses of such studies and protect against the propagation of many false promises concerning the prognostic value of new measurements. Statistical methods used are generally available and can be used for similar analyses in other diseases

    Rescue of Dystrophic Skeletal Muscle by PGC-1α Involves a Fast to Slow Fiber Type Shift in the mdx Mouse

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    Increased utrophin expression is known to reduce pathology in dystrophin-deficient skeletal muscles. Transgenic over-expression of PGC-1α has been shown to increase levels of utrophin mRNA and improve the histology of mdx muscles. Other reports have shown that PGC-1α signaling can lead to increased oxidative capacity and a fast to slow fiber type shift. Given that it has been shown that slow fibers produce and maintain more utrophin than fast skeletal muscle fibers, we hypothesized that over-expression of PGC-1α in post-natal mdx mice would increase utrophin levels via a fiber type shift, resulting in more slow, oxidative fibers that are also more resistant to contraction-induced damage. To test this hypothesis, neonatal mdx mice were injected with recombinant adeno-associated virus (AAV) driving expression of PGC-1α. PGC-1α over-expression resulted in increased utrophin and type I myosin heavy chain expression as well as elevated mitochondrial protein expression. Muscles were shown to be more resistant to contraction-induced damage and more fatigue resistant. Sirt-1 was increased while p38 activation and NRF-1 were reduced in PGC-1α over-expressing muscle when compared to control. We also evaluated if the use a pharmacological PGC-1α pathway activator, resveratrol, could drive the same physiological changes. Resveratrol administration (100 mg/kg/day) resulted in improved fatigue resistance, but did not achieve significant increases in utrophin expression. These data suggest that the PGC-1α pathway is a potential target for therapeutic intervention in dystrophic skeletal muscle
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