This research, aims to analyse the EFQM 2020 Model, supported by a literature review and content analysis, to identify its theoretical foundations and the more relevant novelties compared with the ...2013 version. The EFQM 2020 Model is based on the link between an organisation's purpose and strategy, aligned with the United Nations Sustainable Development Goals (SDGs), to simultaneously deliver performance and ensure transformation, creating enduring value for its key stakeholders and achieving remarkable results. The model adopts a strategic management lens and fits well in the Business Model description. The term excellence is no longer explicitly present, replaced by 'outstanding' (the best it can be). The model is less prescriptive compared to the 2013 version and comprises seven criteria grouped in three dimensions, Direction (why), Execution (how), and Results (what), supported by 23 Criterion Parts and 2 Results Criterion, plus 112 guidance points, and the RADAR assessment tool. Business Excellence Models are mainly designed with contributions from leaders and business experts. Nevertheless, on a theoretical level, several management theories support the EFQM 2020 Model. Although restricted to conceptual and theoretical analysis, this analysis can help academics and business leaders understand this novel model and support future empirical research.
The European Foundation for Quality Management (EFQM) 2020 model is a comprehensive and updated business model that encompasses sustainability and shares features with Industry 4.0, emphasizing ...transformation and improved organizational performance, yet with different theoretical and practical foundations. This research highlights the EFQM 2020 model’s novelties and its relationships/implications with the Industry 4.0 paradigm, contributing to the Quality 4.0 body of knowledge. Several linkages between the EFQM 2020 model and Industry 4.0 have been identified, namely, at the criteria level and guidance points, which can support successful digital transformation by combining quality and excellence with Industry 4.0. However, given the model’s generic and non-prescriptive nature, there is no specific reference to the nine Industry 4.0 pillars. Additionally, the links between direction and organizational culture and leadership criteria and driving performance and transformation are not evident, which might be a concern for business and technology transformation strategies. Managing knowledge, skills, and capabilities is critical for the successful adoption of Industry 4.0. The EFQM model adds a strategic and technologically unbiased perspective to Industry 4.0, providing an integrated business excellence framework for Quality 4.0. With empirical support of the model application, future research is recommended to develop this subject further.
Given the increase in antibiotic-resistant bacteria, alongside the alarmingly low rate of newly approved antibiotics for clinical usage, we are on the verge of not having effective treatments for ...many common infectious diseases. Historically, antibiotic discovery has been crucial in outpacing resistance and success is closely related to systematic procedures-platforms-that have catalyzed the antibiotic golden age, namely the Waksman platform, followed by the platforms of semi-synthesis and fully synthetic antibiotics. Said platforms resulted in the major antibiotic classes: aminoglycosides, amphenicols, ansamycins, beta-lactams, lipopeptides, diaminopyrimidines, fosfomycins, imidazoles, macrolides, oxazolidinones, streptogramins, polymyxins, sulphonamides, glycopeptides, quinolones and tetracyclines. During the genomics era came the target-based platform, mostly considered a failure due to limitations in translating drugs to the clinic. Therefore, cell-based platforms were re-instituted, and are still of the utmost importance in the fight against infectious diseases. Although the antibiotic pipeline is still lackluster, especially of new classes and novel mechanisms of action, in the post-genomic era, there is an increasingly large set of information available on microbial metabolism. The translation of such knowledge into novel platforms will hopefully result in the discovery of new and better therapeutics, which can sway the war on infectious diseases back in our favor.
The move towards a new Circular Economy (CE) economic model has been advocated and supported in Portugal, however, there is limited research on this topic. To address this gap, a quantitative ...research based on an online survey was carried out among 99 Portuguese organizations, encompassing a wide range of sectors and sizes. The results show that CE is regarded as a strategic and relevant issue for profitability and value creation. Furthermore, the perception that it requires the adoption of new business models in addition to the classical “reduce, reuse and recycle” approach is growing. Moreover, based on the hypotheses raised, results suggest that the level of CE adoption is positively impacted by the status of the EMS (Environmental Management System) certification and the willingness to improve the environmental performance and achieve a sustainable business model. However, CE activities are still relatively modest and a friendlier context (fiscal, legal, organizational, etc.) and the stronger support from supply chain agents and consumers are required. Future research should focus on how to design and shape the transition from a linear to a CE economy and to ascertain if the positive attitude towards CE is materialized in changing the way business is done.
Coenzyme Q biosynthesis in health and disease Acosta, Manuel Jesús; Vazquez Fonseca, Luis; Desbats, Maria Andrea ...
Biochimica et biophysica acta,
August 2016, 2016-Aug, 2016-08-00, Letnik:
1857, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Coenzyme Q (CoQ, or ubiquinone) is a remarkable lipid that plays an essential role in mitochondria as an electron shuttle between complexes I and II of the respiratory chain, and complex III. It is ...also a cofactor of other dehydrogenases, a modulator of the permeability transition pore and an essential antioxidant.
CoQ is synthesized in mitochondria by a set of at least 12 proteins that form a multiprotein complex. The exact composition of this complex is still unclear. Most of the genes involved in CoQ biosynthesis (COQ genes) have been studied in yeast and have mammalian orthologues. Some of them encode enzymes involved in the modification of the quinone ring of CoQ, but for others the precise function is unknown. Two genes appear to have a regulatory role: COQ8 (and its human counterparts ADCK3 and ADCK4) encodes a putative kinase, while PTC7 encodes a phosphatase required for the activation of Coq7.
Mutations in human COQ genes cause primary CoQ10 deficiency, a clinically heterogeneous mitochondrial disorder with onset from birth to the seventh decade, and with clinical manifestation ranging from fatal multisystem disorders, to isolated encephalopathy or nephropathy.
The pathogenesis of CoQ10 deficiency involves deficient ATP production and excessive ROS formation, but possibly other aspects of CoQ10 function are implicated.
CoQ10 deficiency is unique among mitochondrial disorders since an effective treatment is available. Many patients respond to oral CoQ10 supplementation. Nevertheless, treatment is still problematic because of the low bioavailability of the compound, and novel pharmacological approaches are currently being investigated. This article is part of a Special Issue entitled ‘EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2–6, 2016’, edited by Prof. Paolo Bernardi.
•Coenzyme Q is an essential component of the mitochondrial respiratory chain and an antioxidant.•Its biosynthesis requires a set of at least 12 proteins encoded by COQ genes.•These proteins form a complex localized to the inner mitochondrial membrane.•Mutations in COQ genes cause primary CoQ10 deficiency.•Many patients with CoQ10 deficiency respond to oral CoQ10 supplementation.
The purpose of this paper is the assessment of the ISO 14001:2015 transition process among Portuguese ISO 14001 certified organizations, including those that successfully have already achieved ISO ...14001:2015 certification. A considerable number of the surveyed companies proceeded with the transition to the ISO 14001:2015 by introducing slight adjustments and were supported by external consultants. Nearly all of the respondent companies (97%) intend to transition until 15th September 2018. The highest ranked reported benefit is the “integrated approach with other management sub-systems” with a well-consolidated perception from the surveyed companies. This is aligned with the ISO 14001:2015 goal of improving the compatibility of management standards supported on the Annex SL. “Alignment with business strategy”, “improved top management commitment” and “improved internal and external communication” are also perceived to obtain significant benefits from ISO 14001:2015. The statistical tests carried out (Kruskal–Wallis) confirmed that the perception of some achieved ISO 14001:2015 certification benefits is dependent on the size of the organization. Concerning the motivations to proceed with certification, results suggest that there is not a particular company profile that is compelled to certify their EMS based on a specific type of motivation (Internal or External). Due to ISO 14001:2015 novelty, these exploratory results should be subjected to additional research confirmation.
A major factor contributing to the etiology of depression is a neurochemical imbalance of the dopaminergic and serotonergic systems, which is caused by persistently high levels of circulating stress ...hormones. Here, a computational model is proposed to investigate the interplay between dopaminergic and serotonergic-kynurenine metabolism under cortisolemia and its consequences for the onset of depression. The model was formulated as a set of nonlinear ordinary differential equations represented with power-law functions. Parameter values were obtained from experimental data reported in the literature, biological databases, and other general information, and subsequently fine-tuned through optimization. Model simulations predict that changes in the kynurenine pathway, caused by elevated levels of cortisol, can increase the risk of neurotoxicity and lead to increased levels of 3,4-dihydroxyphenylaceltahyde (DOPAL) and 5-hydroxyindoleacetaldehyde (5-HIAL). These aldehydes contribute to alpha-synuclein aggregation and may cause mitochondrial fragmentation. Further model analysis demonstrated that the inhibition of both serotonin transport and kynurenine-3-monooxygenase decreased the levels of DOPAL and 5-HIAL and the neurotoxic risk often associated with depression. The mathematical model was also able to predict a novel role of the dopamine and serotonin metabolites DOPAL and 5-HIAL in the ethiology of depression, which is facilitated through increased cortisol levels. Finally, the model analysis suggests treatment with a combination of inhibitors of serotonin transport and kynurenine-3-monooxygenase as a potentially effective pharmacological strategy to revert the slow-down in monoamine neurotransmission that is often triggered by inflammation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The low rate of discovery and rapid spread of resistant pathogens have made antibiotic discovery a worldwide priority. In cell-based screening, the mechanism of action (MOA) is identified after ...antimicrobial activity. This increases rediscovery, impairs low potency candidate detection, and does not guide lead optimization. In this study, high-throughput Fourier-transform infrared (FTIR) spectroscopy was used to discriminate the MOA of 14 antibiotics at pathway, class, and individual antibiotic level. For that, the optimal combinations and parametrizations of spectral preprocessing were selected with cross-validated partial least squares discriminant analysis, to which various machine learning algorithms were applied. This coherently resulted in very good accuracies, independently of the algorithms, and at all levels of MOA. Particularly, an ensemble of subspace discriminants predicted the known pathway (98.6%), antibiotic classes (100%), and individual antibiotics (97.8%) with exceptional accuracy, and similar results were obtained for simulated novel MOA. Even at very low concentrations (1 μg/mL) and growth inhibition (15%), over 70% pathway and class accuracy was achieved, suggesting FTIR spectroscopy can probe the grey chemical matter. Prediction of inhibitory effect was also examined, for which a squared exponential Gaussian process regression yielded a root mean square error of 0.33 and a
R
2
of 0.92, indicating that metabolic alterations leading to growth inhibition are intrinsically reflected on FTIR spectra beyond cell density.
Key points
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Antibiotic MOA and potency estimated with high-throughput FTIR spectroscopy
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Sub-inhibitory MOA identification suggests ability to explore grey chemical matter
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Data analysis optimization improved MOA identification at antibiotic level by 38%
Human cytomegalovirus (HCMV) is an opportunistic pathogen causing disease mainly in immunocompromised patients or after congenital infection. HCMV infection of the respiratory tract leads to ...pneumonitis in the immunocompromised host, which is often associated with a bad clinical course. The related mouse cytomegalovirus (MCMV) likewise exhibits a distinct tropism for the lung and thus provides an elegant model to study host-pathogen interaction. Accordingly, fundamental features of cytomegalovirus (CMV) pneumonitis have been discovered in mice that correlate with clinical data obtained from humans. Recent studies have provided insight into MCMV cell tropism and localized inflammation after infection of the respiratory tract. Accordingly, the nodular inflammatory focus (NIF) has been identified as the anatomical correlate of immune control in lungs. Several hematopoietic cells involved in antiviral immunity reside in NIFs and their key effector molecules have been deciphered. Here, we review what has been learned from the mouse model with focus on the microanatomy of infection sites and antiviral immunity in MCMV pneumonitis.
ISO 9001: 2015 adoption: a multi-country empirical research da Fonseca, Luis Miguel Ciravegna Martins; Domingues, José Pedro; Machado, Pilar Baylina ...
Journal of industrial engineering and management,
01/2019, Letnik:
12, Številka:
1
Journal Article
Odprti dostop
Purpose: This paper aims at identifying obstacles, benefits, leading practices and lessons learned in the transition/certification of the revised standard for quality management systems ISO 9001:2015 ...for organizations in various sector, countries and spanning a range of sizes. Design/methodology/approach: Based on literature review and inputs from experts in management systems certification, a quantitative survey was launched in Portugal, Romania, Switzerland, and Turkey in April 2018, addressed at quality and organizational managers and CEOs from ISO 9001:2015-certified organizations by certification bodies partners of the leading International Quality Network (IQNet). The answers were collected anonymously through an automated online database, until the end of April 2018. The overall response rate was 3.1%, encompassing 222 organizations already certified according to ISO 9001:2015. Findings: The surveyed organizations reported significant benefits from ISO 9001:2015 implementation. Only 3.9% of the respondents considered the 3-year transition period (from September 15, 2015, to September 15, 2018) as too short. The respondents' organizations attended ISO 9001:2015 training and seminars, and collected information from websites, newsletters, books and interpretation guides and directly from certification bodies. Some (29.8%) relied on their own internal resources for the transition processes, while external consultants supported 22.7%. The respondents considered the adoption of risk-based thinking the major difficulty to be overcome, but simultaneously as the major benefit to be realized. The alignment with other management systems, the increased top management commitment, the identification of risks and opportunities and the knowledge management were also reported as significant benefits. The initial timing when organizations started working on the transition process and the activities carried out seem to differ between countries, while the adjustments performed to the existing management systems seem to differ by sector and size of the organization. The benefits attained by the organizations vary according to the perception regarding the information resources made available and organizations should be aware of the advantages of early planning. The organizations that rated the benefits of ISO 9001:2015 adoption higher considered the information resources as adequate and started working with ISO 9001:2015 at an earlier stage, while those that rated the benefits lower stated that the information resources were made available too late. The organizations that successfully managed the ISO 9001:2015 transition/certification process were the ones that attended ISO 9001:2015 training courses and seminars and got useful information from their certification body. This research highlights the relevance of the geographical context, of the organization size and the sector for successful adoption of ISO 9001:2015. The identification and promotion of resources that led to the highest benefits are worth pursuing. The replication of this study can add a time perspective and the assessment if these perceptions are expected to materialize into tangible results such as cost benefits and higher customer satisfaction. Research limitations/implications: Due to the novelty of ISO 9001:2015, these results should be subjected to additional validation and longitudinal analyses. Although measures have been taken to minimize possible bias errors from both non-respondents', and respondents' subjectivity, these limitations of the survey methodology should be acknowledged. Practical implications: The findings of this research provide standardization and certification bodies and quality management systems practitioners with leading practices in the implementation of ISO 9001:2015 and guidance for an efficient and effective transition/adoption. Originality/value: This investigation contributes to the ISO 9001:2015 body of knowledge by mapping the transition/certification processes with a multi-country perspective. The results empirically validate the potential value of transitioning or adopting ISO 9001:2015 and give insights on the implementation methodologies, leading practices to follow, difficulties to overcome and benefits to realize, to maximize the success of ISO 9001:2015 adoption.
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