Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

El circuit comercial de Barcino: reflexions al voltant de les marques amfòriques

Barcino és encara avui una ciutat romana poc coneguda de la província Tarraconense, que segons la majoria d’especialistes fou fundada per raons polítiques. Malgrat això, una anàlisi detallada de les característiques econòmiques suggereixen que es va crear com a resultat de necessitats comercials, ja que es localitzava en una de les millors zones portuàries del NE de la península. L’article present pretén reconstruir tot el circuit comercial de Barcino a partir de les nombroses estampilles d’àmfores trobades en les excavacions. Aquestes marques comercials no solament evidencien una pròspera producció de vi en l’àrea, sinó també la corresponent demanda externa.

Disseny de circuit de proves de traçabilitat amb rfid

ITENE és un institut tecnològic de recerca situat a Paterna (València). Té una plantapilot especialitzada en logística on les empreses que ho vulguin (mitjançant convenis,en règim de lloguer, etc.), poden utilitzar les instal•lacions (magatzem intel•ligent,aplicacions RFID, etc.), per provar els seus productes i simular processos de logística itraçabilitat.En aquesta planta s'ha detectat la necessitat de poder provar nous productes cometiquetes, detectors i processadors equipats amb tecnologia RFID (Identificació perRadiofreqüència). Aquesta tecnologia consisteix en passar informació que conté unaetiqueta “intel•ligent” cap a un terminal (PC) mitjançant uns detectors que, perproximitat, poden llegir la informació. Per exemple, quan un camió ple de mercaderiesprèviament etiquetades, passa per un pòrtic amb detectors RFID, es genera unainformació que passa directament a un terminal. Al moment es pot saber què porta elcamió, quantitat, color, mides, etc. Si això es combina amb un ERP, es pot descomptarde l'estoc en temps real. De fet s'utilitza per moltes aplicacions logística, control deprocessos de fabricació, traçabilitat de productes, etc.Per aquest motiu, ITENE, mitjançant el contacte de AIFOS SOLUTIONS S.L (empresaespecialitzada en RFID) ha encarregat un sistema de transportadors de banda per provarnoves solucions.L'objecte del present projecte consisteix en el disseny i automatització d'un sistema de 4cintes transportadores 2 elevadors per tal de fer un circuit tancat per moure caixes en un“bucle” de forma automàtica. L'objectiu és “llençar” caixes plenes de productes (etiquetats amb RFID) mitjançant untransportador equipat amb un pòrtic que té instal•lats diversos detectors de radiofreqüència,i poder-ne provar la correcta detecció a diferents velocitats. Un “buffer” s'encarrega desubministrar les caixes d'una en una que, un cop acabat el circuit, tornen al lloc d'on hansortit. Per donar un producte per bo, es realitzen tests de diverses hores i se n'obté unaestadística de lectures bones/dolentes. Si la ràtio és la desitjada es dóna per bo elproducte.Per aconseguir un disseny correcte s'ha utilitzat diferents eines CAD per dimensionar elsistema de transportadors i els seus elements. Tota l'aplicació està realitzada en 3Dmitjançant el software AutoCAD 3D. L'abast d'aquest projecte inclourà la solució mecànica i pneumàtica del sistema, aixícom el seu muntatge i tot el referent a les normes de seguretat per tal que el sistemacompleixi la normativa referida a la seguretat de màquines

An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'

Material and methods. Methylone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (15 and 30 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results. Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α = 1.95 h− 1 and β = 0.72 h− 1. For oral administration, peak methylone concentrations were achieved between 0.5 and 1 h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42 ± 0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate. Discussion. Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.

An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'

Material and methods. Methylone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (15 and 30 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results. Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α = 1.95 h− 1 and β = 0.72 h− 1. For oral administration, peak methylone concentrations were achieved between 0.5 and 1 h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42 ± 0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate. Discussion. Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.

Climate change impacts on lakes: an integrated ecological perspective based on a multi-faceted approach, with special focus on shallow lakes

Freshwater ecosystems and their biodiversity are presently seriously threatened by global development and population growth, leading to increases in nutrient inputs and intensification of eutrophication-induced problems in receiving fresh waters, particularly in lakes. Climate change constitutes another threat exacerbating the symptoms of eutrophication and species migration and loss. Unequivocal evidence of climate change impacts is still highly fragmented despite the intensive research, in part due to the variety and uncertainty of climate models and underlying emission scenarios but also due to the different approaches applied to study its effects. We first describe the strengths and weaknesses of the multi-faceted approaches that are presently available for elucidating the effects of climate change in lakes, including space-for-time substitution, time series, experiments, palaeoecology and modelling. Reviewing combined results from studies based on the various approaches, we describe the likely effects of climate changes on biological communities, trophic dynamics and the ecological state of lakes. We further discuss potential mitigation and adaptation measures to counteract the effects of climate change on lakes and, finally, we highlight some of the future challenges that we face to improve our capacity for successful prediction.

Systems Medicine and Integrated Care to Combat Chronic Noncommunicable Diseases.

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.

Integrated regulation of the type III secretion system and other virulence determinants in Ralstonia solanacearum

In many plant and animal bacterial pathogens, the Type III secretion system (TTSS) that directly translocates effector proteins into the eukaryotic host cells is essential for the development of disease. In all species studied, the transcription of the TTSS and most of its effector substrates is tightly regulated by a succession of consecutively activated regulators. However, the whole genetic programme driven by these regulatory cascades is still unknown, especially in bacterial plant pathogens. Here, we have characterised the programme triggered by HrpG, a host-responsive regulator of the TTSS activation cascade in the plant pathogen Ralstonia solanacearum. We show through genome-wide expression analysis that, in addition to the TTSS, HrpG controls the expression of a previously undescribed TTSS-independent pathway that includes a number of other virulence determinants and genes likely involved in adaptation to life in the host. Functional studies revealed that this second pathway co-ordinates the bacterial production of plant cell wall-degrading enzymes, exopolysaccharide, and the phytohormones ethylene and auxin. We provide experimental evidence that these activities contribute to pathogenicity. We also show that the ethylene produced by R. solanacearum is able to modulate the expression of host genes and can therefore interfere with the signalling of plant defence responses. These results provide a new, integrated view of plant bacterial pathogenicity, where a common regulator activates synchronously upon infection the TTSS, other virulence determinants and a number of adaptive functions, which act co-operatively to cause disease.

Macrofossils in Raraku Lake (Easter Island) integrated with sedimentary and geochemical records towards a palaeoecological synthesis for the last 34,000 years

Macrofossil analysis of a composite 19 m long sediment core from Rano Raraku Lake (Easter Island)was related to litho-sedimentary and geochemical features of the sediment. Strong stratigraphical patterns are shown by indirect gradient analyses of the data. The good correspondence between the stratigraphical patterns derived from macrofossil (Correspondence Analysis) and sedimentary and geochemical data (Principal Component Analysis) shows that macrofossil associations provide sound palaeolimnological information in conjunction with sedimentary data. The main taphonomic factors in fluencing the macrofossil assemblages are run-off from the catchment, the littoral plant belt, and the depositional environment within the basin. Five main stages during the last 34,000 calibrated years BP (cal yr BP) are characterised from the lithological, geochemical, and macrofossil data. From 34 to 14.6 cal kyr BP (last glacial period) the sediments were largely derived from the catchment, indicating a high energy lake environment with much erosion and run-off bringing abundant plant trichomes, lichens, and mosses into the centre of Raraku Lake.

Preliminary integrated magnetostratigraphic and biostratigraphic correlation in the Miocene Lorca Basin (Murcia, SE Spain).

The Lorca basin is one of the Neogene basins OS South Eastern Spain. The infilling Tortonian-Messinian deposits are mainly composed OS marls and reach up to 1,200 m in thickness. A biostratigraphic survey OS these deposits, assisted by the determination OS the magnetic polarity reversal pattern Sor most OS these deposits (900 m), has enabled the Tortonian-Messinian chronostratigraphy to be precised. The close sampling space for biostratigraphic determination has enabled the accurate location OS Sour main biostratigraphic events than can be correlated with charactenstic events of the Mediterranean biostratigraphic Zones. In addition, the location OS the TortonianNessinian boundary has been accurately placed at some 150 m below the main gypsurn unit outcropping in the basin. The integrated bio-magnetostratigraphic data fiom the studied section allows a tentative interpretation OS the identified magnetozones. Thus, a correlation to the Geomagnetic Polarity Time Scale is presented for more than 900 m of pre-evaporite Miocene stratigraphic succession fiom the Lorca basin. Moreover, about 15' OS anticlockwise rotation has been detected. Its significance is evaluated in the basin geodynamic framework.

Landscape Systems and Human Land-Use Interactions in Mediterranean Highlands and Littoral Plains during the Late Holocene: Integrated Analysis from the InterAmbAr Project (North-Eastern Catalonia).

The main goal of the InterAmbAr reseach project is to analyze the relationships between landscape systems and human land-use strategies on mountains and littoral plains from a long-term perspective. The study adopts a high resolution analysis of small-scale study areas located in the Mediterranean region of north-eastern Catalonia. The study areas are distributed along an altitudinal transect from the high mountain (above 2000m a.s.l.) to the littoral plain of Empordà (Fig. 1). High resolution interdisciplinary research has been carried out from 2010, based on the integration of palaeoenvironmental and archaeological data. The micro-scale approach is used to understand human-environmental relationships. It allows better understanding of the local-regional nature of environmental changes and the synergies between catchment-based systems, hydro-sedimentary regimes, human mobility, land-uses, human environments, demography, etc.

An integrated model of adoption and development of e-commerce in companies

Since the mid-1990s researchers have sought to understand why some firms embark on e-commerceoperations on the Internet while others prefer to wait and see how events unfold. We still have todetermine which variables contribute to explaining the extent to which firms use e-commerce, giventhat to date the literature has not yet offered conclusive evidence on this question. The current workaims to provide an integrated vision of the set of factors influencing the e-commerce adoptionprocess. We use a sample of 2,038 firms of all types that trade their products either with otherorganizations or with end-consumers.

DAI-DEPUR: an integrated and distributed architecture for wastewater treatment plants supervision

The activated sludge process - the main biological technology usually applied towastewater treatment plants (WWTP) - directly depends on live beings (microorganisms), and therefore on unforeseen changes produced by them. It could be possible to get a good plant operation if the supervisory control system is able to react to the changes and deviations in the system and can take thenecessary actions to restore the system’s performance. These decisions are oftenbased both on physical, chemical, microbiological principles (suitable to bemodelled by conventional control algorithms) and on some knowledge (suitable to be modelled by knowledge-based systems). But one of the key problems in knowledge-based control systems design is the development of an architecture able to manage efficiently the different elements of the process (integrated architecture), to learn from previous cases (spec@c experimental knowledge) and to acquire the domain knowledge (general expert knowledge). These problems increase when the process belongs to an ill-structured domain and is composed of several complex operational units. Therefore, an integrated and distributed AIarchitecture seems to be a good choice. This paper proposes an integrated and distributed supervisory multi-level architecture for the supervision of WWTP, that overcomes some of the main troubles of classical control techniques and those of knowledge-based systems applied to real world systems

Microcontroller-based interface circuit for inductive sensors

This work proposes a fully-digital interface circuit for the measurement of inductive sensors using a low-cost microcontroller (µC) and without any intermediate active circuit. Apart from the µC and the sensor, the circuit just requires an external resistor and a reference inductance so that two RL circuits with a high-pass filter (HPF) topology are formed. The µC appropriately excites such RL circuits in order to measure the discharging time of the voltage across each inductance (i.e. sensing and reference) and then it uses such discharging times to estimate the sensor inductance. Experimental tests using a commercial µC show a non-linearity error (NLE) lower than 0.5%FSS (Full-Scale Span) when measuring inductances from 1 mH to 10 mH, and from 10 mH to 100 mH.