Methodological approach to study the dynamics of production networks: Discrete-event simulation modelling

This paper shows how discrete-event simulation represents an appropriate tool for approaching the dynamics of production networks. Three important factors influencing production network dynamics, specifically finite production capacity, manufacturing lead time, and its variability are discussed and a basic discrete-event simulation model is presented. Such model, which in its basic form represents a simple retail/distribution two-stage supply chain, is then extended in order to take into account those factors that can not be included in a classical control theoretical model

Optimal planning and campaign scheduling of biopharmaceutical processes using a continuous-time formulation

This work addresses the optimal planning and campaign scheduling of biopharmaceutical manufacturing processes, considering multiple operational characteristics, such as the campaign schedule of batch and/or continuous process steps, multiple intermediate deliveries, sequence dependent changeovers operations, product storage restricted to shelf-life limitations, and the track-control of the production/campaign lots due to regulatory policies. A new mixed integer linear programing (MILP) model, based on a Resource Task Network (RTN) continuous time single-grid formulation, is developed to comprise the integration of all these features. The performance of the model features is discussed with the resolution of a set of industrial problems with different data sets and process layouts, demonstrating the wide application of the proposed formulation. It is also performed a comparison with a related literature model, showing the advantages of the continuous-time approach and the generality of our model for the optimal production management of biopharmaceutical processes

Estudio bibliométrico sobre disertaciones y tesis en enfermería con aproximación fenomenológica: tendencia y perspectivas

This study aimed to analyze the scientific production of nursing dissertations and theses with a phenomenological approach published from 1981 to 2002. A descriptive, retrospective and bibliometric research was carried out. The material analysis, which is part of the database of the catalogue Information on Nursing Research and Researchers, resulted in 217 studies, 71,9% from the master's course and 28,1% from the doctoral course. Among the obtained results, it stands out that the theoretical-philosophical reference chosen to support the data discussion found in investigations has not been used emphatically. There is a need to discuss the unveiled data, through the subjects' discourse, in the light of the philosophical reference framework mentioned in the research trajectory.Este trabajo tuvo como objetivo analizar la producción científica sobre disertaciones y tesis de enfermería con aproximación fenomenológica publicadas de 1981 a 2002. Fue una investigación del tipo descriptivo, retrospectivo y bibliométrico. El análisis del material perteneciente a la base de datos del catálogo Informaciones sobre Investigaciones y Investigadores en Enfermería resultó en 217 estudios: el 71,9% de maestría y el 28,1% del doctorado. Entre los resultados alcanzados, se destaca que el referencial teórico-filosófico elegido para soportar el análisis de datos encontrados en las investigaciones no ha sido utilizados con énfasis. Se destaca la necesidad de discutir los datos encontrados a través del discurso de los sujetos, a la luz del referencial teórico-filosófico mencionado en la trayectoria de investigación.Este estudo teve por objetivo analisar a produção científica sobre dissertações e teses de enfermagem com abordagem fenomenológica, publicadas de 1981 a 2002. Trata-se de pesquisa do tipo descritiva, retrospectiva e bibliométrica. A análise do material, que consta na base de dados do catálogo Informações sobre Pesquisas e Pesquisadores em Enfermagem, resultou em 217 estudos: 71,9% do curso de mestrado e 28,1% do curso de doutorado. Dentre os resultados obtidos destaca-se que o referencial teórico-filosófico escolhido para subsidiar a discussão dos dados encontrados nas investigações não tem sido utilizado com ênfase. Aponta-se a necessidade de discutir os dados desvelados, por meio dos discursos dos sujeitos, à luz do referencial teórico-filosófico, mencionado na trajetória da pesquisa

Using self-organizing maps to investigate environmental factors regulating colony size and breeding success of the White Stork (Ciconia ciconia)

We studied variations in the size of breeding colonies and in breeding performance of White Storks Ciconia ciconia in 2006–2008 in north-east Algeria. Each colony site was characterized using 12 environmental variables describing the physical environment, land-cover categories, and human activities, and by three demographic parameters: the number of breeding pairs, the number of pairs with chicks, and the number of fledged chicks per pair. Generalized linear mixed models and the self-organizing map algorithm (SOM, neural network) were used to investigate effects of biotic, abiotic, and anthropogenic factors on demographic parameters and on their relationships. Numbers of breeding pairs and of pairs with chicks were affected by the same environmental factors, mainly anthropogenic, which differed from those affecting the number of fledged chicks per pair. Numbers of fledged chicks per pair was not affected by colony size or by the number of nests with chicks. The categorization of the environmental variables into natural and anthropogenic, in connection with demographic parameters, was relevant to detect factors explaining variation in colony size and breeding parameters. The SOM proved a relevant tool to help determine actual dynamics in White Stork colonies, and thus to support effective conservation decisions at a regional scale

Observation of Bc+ →j /ψD (∗)K (∗) decays

A search for the decays B+c→J/ψD(*)0K+ and B+c→J/ψD(*)+K*0 is performed with data collected at the LHCb experiment corresponding to an integrated luminosity of 3 fb−1. The decays B+c→J/ψ0K+ and B+c→J/ψD*0K+ are observed for the first time, while first evidence is reported for the B+c→JψD*+K*0 and B+c→J/ψD+K*0 decays. The branching fractions of these decays are determined relative to the B+c→J/ψπ+ decay. The B+c mass is measured, using the J/ψD0K+ final state, to be 6274.28±1.40(stat)±0.32(syst) MeV/c2. This is the most precise single measurement of the B+c mass to date

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013

Intricate macrophage-colorectal cancer cell communication in response to radiation

Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients' treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy

Individual-environment interactions in swimming: The smallest unit for analysing the emergence of coordination dynamics in performance?

Displacement in competitive swimming is highly dependent on fluid characteristics, since athletes use these properties to propel themselves. It is essential for sport scientists and practitioners to clearly identify the interactions that emerge between each individual swimmer and properties of an aquatic environment. Traditionally, the two protagonists in these interactions have been studied separately. Determining the impact of each swimmer’s movements on fluid flow, and vice versa, is a major challenge. Classic biomechanical research approaches have focused on swimmers’ actions, decomposing stroke characteristics for analysis, without exploring perturbations to fluid flows. Conversely, fluid mechanics research has sought to record fluid behaviours, isolated from the constraints of competitive swimming environments (e.g. analyses in two-dimensions, fluid flows passively studied on mannequins or robot effectors). With improvements in technology, however, recent investigations have focused on the emergent circular couplings between swimmers’ movements and fluid dynamics. Here, we provide insights into concepts and tools that can explain these on-going dynamical interactions in competitive swimming within the theoretical framework of ecological dynamics

eLearning resources to supplement postgraduate neurosurgery training.

BACKGROUND: In an increasingly complex and competitive professional environment, improving methods to educate neurosurgical residents is key to ensure high-quality patient care. Electronic (e)Learning resources promise interactive knowledge acquisition. We set out to give a comprehensive overview on available eLearning resources that aim to improve postgraduate neurosurgical training and review the available literature. MATERIAL AND METHODS: A MEDLINE query was performed, using the search term "electronic AND learning AND neurosurgery". Only peer-reviewed English-language articles on the use of any means of eLearning to improve theoretical knowledge in postgraduate neurosurgical training were included. Reference lists were crosschecked for further relevant articles. Captured parameters were the year, country of origin, method of eLearning reported, and type of article, as well as its conclusion. eLearning resources were additionally searched for using Google. RESULTS: Of n = 301 identified articles by the MEDLINE search, n = 43 articles were analysed in detail. Applying defined criteria, n = 28 articles were excluded and n = 15 included. Most articles were generated within this decade, with groups from the USA, the UK and India having a leadership role. The majority of articles reviewed existing eLearning resources, others reported on the concept, development and use of generated eLearning resources. There was no article that scientifically assessed the effectiveness of eLearning resources (against traditional learning methods) in terms of efficacy or costs. Only one article reported on satisfaction rates with an eLearning tool. All authors of articles dealing with eLearning and the use of new media in neurosurgery uniformly agreed on its great potential and increasing future use, but most also highlighted some weaknesses and possible dangers. CONCLUSION: This review found only a few articles dealing with the modern aspects of eLearning as an adjunct to postgraduate neurosurgery training. Comprehensive eLearning platforms offering didactic modules with clear learning objectives are rare. Two decades after the rise of eLearning in neurosurgery, some promising solutions are readily available, but the potential of eLearning has not yet been sufficiently exploited

Climate, history, society over the last millennium in southeast Africa

Climate variability has been causally linked to the transformation of society in pre-industrial southeast Africa. A growing critique, however, challenges the simplicity of ideas that identify climate as an agent of past societal change; arguing instead that the value of historical climate–society research lies in understanding human vulnerability and resilience, as well as how past societies framed, responded and adapted to climatic phenomena. We work across this divide to present the first critical analysis of climate–society relationships in southeast Africa over the last millennium. To achieve this, we review the now considerable body of scholarship on the role of climate in regional societal transformation, and bring forward new perspectives on climate–society interactions across three areas and periods using the theoretical frameworks of vulnerability and resilience. We find that recent advances in paleoclimatology and archaeology give weight to the suggestion that responses to climate variability played an important part in early state formation in the Limpopo valley (1000–1300), though evidence remains insufficient to clarify similar debates concerning Great Zimbabwe (1300–1450/1520). Written and oral evidence from the Zambezi-Save (1500–1830) and KwaZulu-Natal areas (1760–1828) nevertheless reveals a plurality of past responses to climate variability. These were underpinned by the organization of food systems, the role of climate-related ritual and political power, social networks, and livelihood assets and capabilities, as well as the nature of climate variability itself. To conclude, we identify new lines of research on climate, history and society, and discuss how these can more directly inform contemporary African climate adaptation challenges