Improving subsidiaries' innovation through knowledge inflows from headquarters and peer subsidiaries

This study develops a conceptual model that compares the intensity of the impact of knowledge inflows from peer subsidiaries and from the headquarters in the promotion of a focal subsidiary's innovation activities, moderated by socialization mechanisms and national cultural distance. The authors test hypotheses with a dataset comprised of survey data from 202 multinational corporations (MNC) Portuguese subsidiaries. The results indicate that although knowledge inflows from both the headquarters and peer subsidiaries promote the focal subsidiary's innovations capabilities, headquarters' knowledge transfer is a superior and more efficient source of knowledge in the promotion of a subsidiary's new product development. Moreover, socialization mechanisms, both lateral and vertical integrating mechanisms, act as critical instruments that facilitate the incorporation of the incoming knowledge flows into innovation. This study extends the literature on knowledge transfer in MNCs by exploring how two sources of knowledge transfer, the headquarters and peer subsidiaries, influence a focal subsidiary's new product development, investigating socialization mechanisms and national cultural distance moderating effects.info:eu-repo/semantics/publishedVersio

Model discrimination in time-course kinetics : the glyoxalase pathway in S. cerevisiae

Tese de doutoramento, Bioquímica (Bioquímica Teórica), Universidade de Lisboa, Faculdade de Ciências, 2010.The present work addresses the problem of model discrimination in enzyme kinetics. Frequently, more than one kinetic model is considered during the characterization of an enzymatic reaction or a metabolic pathway. The statistical selection of a model may be difficult if the candidate models fit the experimental data with very similar fitting scores. Since each model corresponds to a different possible mechanism of the studied process, model selection also reflects the choice of a particular mechanism. In addition, predictions given by models with equal fitting scores may be different. The glyoxalase system is a metabolic pathway that has been studied using two alternative kinetic models. These models could not be discriminated despite extensive kinetic experiments and an alternative branched mechanism combining the two models has been proposed. This pathway is therefore ideal for model discrimination research in Biochemistry. The glyoxalase pathway comprises the enzymes glyoxalase I and glyoxalase II. Glyoxalase I catalyzes the isomerization of the hemithioacetal that forms from the condensation of methylglyoxal (a by-­product of glycolysis) and glutathione to S-­D-­lactoylglutathione. Glyoxalase II catalyzes the hydrolysis of S-­D-­glutathione to D-­ lactate and glutathione. The methylglyoxal-­glutathione hemithioacetal forms spontaneously without the presence of enzymes. Therefore the glyoxalase I reaction can be described either as irreversible single-­substrate or as irreversible two-­substrate, considering that the hemithioacetal forms before binding the enzyme or that it forms in the active centre of the enzyme after sequential binding of glutathione and methylglyoxal, respectively. The glyoxalase system is the most important catabolic pathway for methylglyoxal. Methylglyoxal is a toxic agent due to its ability to react with proteins and nucleic acid amine groups that leads to formation of advanced glycation end-­products. Therefore the glyoxalase pathway was suggested to be a potential dug target for its cellular defensive role against methylglyoxal. An introduction to the subjects developed through this dissertation is given in chapter 1, covering the state of art of research on the glyoxalase pathway and methylglyoxal metabolism and on relevant mathematical and computational methods for model analysis and discrimination. In chapter 2 the glyoxalase system is investigated by analyzing the algebraic solutions of the rate equations describing the pathway at steady state. The two mentioned glyoxalase I kinetic models were used in this approach. It is observed that for the existence of a steady state a minimum amount of glutathione must be available;; in addition, glyoxalase I and II activities must exceed thresholds higher than the flux of the pathway. It is shown that methylglyoxal steady-­state concentration is not sensitive to variations of glyoxalase II activity but varies significantly with total glutathione concentration and methylglyoxal formation rate. Sensitivity to glyoxalase I activity depends on the kinetic model describing the enzyme: highly sensitivity if the two-­ substrate model is used but not so for the one-­substrate model. The pathway seems to operate very far from the conditions of disruption of the physiological steady state to assure a very low methylglyoxal concentration and a fast regeneration and high concentration of free glutathione. Time-­course kinetic studies with purified yeast enzyme and yeast permeabilized cells are described in chapter 3. Akaike’s information criterion and residual analysis are used to discuss the selection of the most appropriate kinetic model for glyoxalase I. Parameter least-­square estimates for this study are obtained with a combination of the stochastic Differential Evolution with the deterministic downhill-­simplex optimization algorithms. Although the two-­substrate model performs slightly better for the purified enzyme data, the Akaike score differences for both data sets and the residual analysis for the permeabilized cell data are not conclusive. A method developed to design optimized experimental conditions for model discrimination is explained in chapter 4. The method employs a multiobjective optimization algorithm (the Generalized Differential Evolution, generation 3) to search for the experimental conditions that maximize the divergence between the reaction time courses predicted by the models. The Kullback-­Leibler distance is the measure of divergence employed. The combination of the chosen algorithm and divergence criterion is successful in finding solutions that result in very different predictions from the two models for glyoxalase I in the presence of glyoxalase II, proving to be useful for planning model discrimination experiments. The importance of keeping a high free glutathione concentration seems to establish the properties of the glyoxalase pathway identified in chapter 2. Glutathione is also a key antioxidant and its oxidized form is reduced through the glutathione reductase system at the expense of NADPH. Indeed, the pyridine nucleotides NADPH and NADH have crucial metabolic roles. NADH, formed mainly in catabolic reactions, is the substrate of the respiratory chain and therefore it ultimately supplies the synthesis of ATP. NADPH is the main reducing agent in biosynthetic pathways. In addition, the pyridine nucleotides are among the metabolites that participate in a larger number of reactions in the cell. Therefore it is important to understand the effects of concentration changes of these metabolites. In chapter 5 perturbations to pyridine nucleotide concentrations are studied in living yeast cells cultured in bioreactors. The results for five recombinant S. cerevisiae strains overexpressing a cytosolic NADH oxidase, a mitochondrial NADH oxidase, a cytosolic NADH kinase, a mitochondrial NADH kinase and a cytosolic soluble pyridine nucleotide transhydrogenase are discussed. Extracellular and intracellular metabolite measurements and a stoichiometric model are used to assess the consequences of such perturbations, unveiling how metabolism in intact cells adapts to different redox conditions. Strains with enhanced NADH oxidation in the cytosol show a lower glycerol production. On the other hand enhanced NADH consumption in the mitochondrion lowers ethanol production and enhances ATP synthesis efficiency. The results presented here show that different kinetic models may fit experimental data equally well, making the selection of one model extremely. An original contribution is established to aid planning experiments for model discrimination. In addition, a broad characterization of the effects of perturbations to pyridine nucleotide metabolism is given, which is valuable to understand the complex response of yeast’s metabolic network, with direct biotechnological application.Fundação para a Ciência e Tecnologia – Ministério da Ciência, Tecnologia e Ensino Superior, Portugal (SFRH/BD/21947/2005

Perceção de risco de incêndios florestais em Portugal: o caso dos agentes com intervenção turística no Parque Natural do Vale do Guadiana

A presente dissertação é um estudo exploratório com o principal objetivo de apurar a perceção de risco de incêndios por parte dos operadores do PNVG - Parque Natural do Vale do Guadiana. Para maximizar a dimensão da amostra, foi aplicado um inquérito a 35 entidades com atividades em turismo, em caça e agricultura, assim como aos membros da Comissão de Cogestão do PNVG. Para a análise e interpretação dos dados foram utilizadas a análise quantitativa e análise qualitativa. Os resultados verificaram que em diferentes dimensões os setores de atividade divergem de opiniões, sem nunca deixarem de mostrar preocupação e esforço na procura e melhoria de estratégias de mitigação na ocorrência de incêndios. A análise qualitativa salientou a preocupação com a biodiversidade e com a manutenção e limpeza do PNVG. O estudo indicou a importância que o setor turístico deverá conferir aos impactos causados pela possível ocorrência de incêndios florestais; - Perception of risk of forest fires in Portugal: the case of tourist agents with intervention in the Guadiana Valley Natural Park. Abstract: The dissertation is an exploratory study aiming to ascertain the perception of fire risk by operators of the PNVG - Guadiana Valley Natural Park. To maximize the sample size, a survey was applied to 35 entities with activities in tourism, hunting and agriculture, as well as to members of the PNVG's Co-management Commission. For data analysis and interpretation, quantitative analysis and qualitative analysis were used. The results showed that in different dimensions the activity sectors have different opinions, but never fail to show concern and efforts in the search and improvement of mitigation strategies in the occurrence of fires. The qualitative analysis highlights the concern with biodiversity, as well as with the maintenance and cleaning of the PNVG. The study allowed verifying the degree of importance that the tourism sector should give to the impacts caused by the possible occurrence of forest fires

Co-creation, innovation, decision-making, tech-transfer, and sustainability actions

Funding Information: Open access funding provided by FCT|FCCN (b-on). This work was funded by the European Union’s Horizon 2020 program [H2020-SC5-2019–2]—869520 NextLand, [H2020-SPACE-202]—101004362 NextOcean, Fundação para a Ciência e a Tecnologia (UIDB/00124/2020 and Social Sciences DataLab, PINFRA/22209/2016), POR Lisboa and POR Norte (Social Sciences DataLab, PINFRA/22209/2016). Publisher Copyright: © 2023, The Author(s).European Community (EC) Horizon-funded projects and Earth Observation-based Consortia aim to create sustainable value for Space, Land, and Oceans. They typically focus on addressing Sustainable Development Goals (SDGs). Many of these projects (e.g. Commercialization and Innovation Actions) have an ambitious challenge to ensure that partners share core competencies to simultaneously achieve technological and commercial success and sustainability after the end of the EC funds. To achieve this ambitious challenge, Horizon projects must have a proper governance model and a systematized process that can manage the existing paradoxical tensions involving numerous European partners and their respective agendas and stakeholders. This article presents the VCW-Value Creation Wheel (Lages in J Bus Res 69: 4849–4855, 2016), as a framework that has its roots back in 1995 and has been used since 2015 in the context of numerous Space Business, Earth Observation, and European Community (EC) projects, to address complex problems and paradoxical tensions. In this article, we discuss six of these paradoxical tensions that large Horizon Consortia face in commercialization, namely when managing innovation ecosystems, co-creating, taking digitalization, decision-making, tech-transfer, and sustainability actions. We discuss and evaluate how alliance partners could find the optimal balance between (1) cooperation, competition, and coopetition perspectives; (2) financial, environmental, and social value creation; (3) tech-push and market-pull orientations; (4) global and local market solutions; (5) functionality driven and human-centered design (UX/UI); (6) centralized and decentralized online store approaches. We discuss these challenges within the case of the EC H2020 NextLand project answering the call for greening the economy in line with the Sustainable Development Goals (SDGs). We analyze NextLand Online Store, and its Business and Innovation Ecosystem while considering the input of its different stakeholders, such as NextLand’s commercial team, service providers, users, advisors, EC referees, and internal and external stakeholders. Preliminary insights from a twin project in the field of Blue Economy (EC H2020 NextOcean), are also used to support our arguments. Partners, referees, and EC officers should address the tensions mentioned in this article during the referee and approval processes in the pre-grant and post-grant agreement stages. Moreover, we propose using the Value Creation Wheel (VCW) method and the VCW meta-framework as a systematized process that allows us to co-create and manage the innovation ecosystem while engaging all the stakeholders and presenting solutions to address these tensions. The article concludes with theoretical implications and limitations, managerial and public policy implications, and lessons for Horizon Europe, earth observation, remote sensing, and space business projects.publishersversionpublishe

Improving subsidiaries' innovation through knowledge inflows from headquarters and peer subsidiaries

This study develops a conceptual model that compares the intensity of the impact of knowledge inflows from peer subsidiaries and from the headquarters in the promotion of a focal subsidiary's innovation activities, moderated by socialization mechanisms and national cultural distance. The authors test hypotheses with a dataset comprised of survey data from 202 multinational corporations (MNC) Portuguese subsidiaries. The results indicate that although knowledge inflows from both the headquarters and peer subsidiaries promote the focal subsidiary's innovations capabilities, headquarters' knowledge transfer is a superior and more efficient source of knowledge in the promotion of a subsidiary's new product development. Moreover, socialization mechanisms, both lateral and vertical integrating mechanisms, act as critical instruments that facilitate the incorporation of the incoming knowledge flows into innovation. This study extends the literature on knowledge transfer in MNCs by exploring how two sources of knowledge transfer, the headquarters and peer subsidiaries, influence a focal subsidiary's new product development, investigating socialization mechanisms and national cultural distance moderating effects.authorsversionpublishe

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research