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The Fifth Generation (5G) mobile networking coupled with Internet of Things (IoT) can provide innovative solutions for a wide range of uses cases. The flexibility of virtualized, softwarized and multi-tenant infrastructures and the high performance promised by 5G technology are key to cope with the deployment of the IoT use cases demanded by various vertical businesses. Such 5G IoT use cases incur challenging Quality of Service (QoS) requirements especially connectivity for millions of IoT devices to achieve massive Machine-Type Communication (mMTC). In addition, network slicing is a key enabling technology in 5G multi-tenant networks to create logical virtualized networks for delivering customised solutions to meet diverse QoS requirements. This work presents a 5G IoT framework with network slicing capabilities able to manage a vast number of heterogeneous IoT network slices dynamically on demand. The proposed solution has been empirically tested and validated in five realistic vertical-oriented IoT use cases. The achieved results demonstrate a excellent stability, isolation and scalability while being able to meet extreme QoS requirements even in the most congested and stressful scenarios.

Network slicing is a primary Fifth-Generation (5G) mobile networking technology to create virtualised and softwarised logical networks for various vertical businesses with diverging Quality of Service (QoS) requirements. Meanwhile, there is a clear gap in providing network slicing capabilities in 5G multi-tenant networks to enable guaranteed QoS in terms of well-defined network metrics for the multiple tenants sharing the same physical infrastructure. This article designs and implements novel software data path architecture that enables such network slicing with assured QoS in 5G multi-tenant networks. Highly flexible and customisable definition of network slicing is also allowed to be aligned with different existing definitions on demand and at run time. The proposed architecture has been prototyped based on the popular Open Virtual Switch (OVS), and empirically validated to demonstrate the deployment and management of network slices with the above capabilities. Intensive scalability results are provided where more than 8,192 network slices are achieved simultaneously with warranted QoS through performance isolation in terms of bandwidth and delay in a real softwarised 5G multi-tenant infrastructure at speeds of up to 10 Gbps.

Background: Plasma concentration of natalizumab falls above the therapeutic threshold in many patients who, therefore, receive more natalizumab than necessary and have higher risk of progressive multifocal leukoencephalopathy.Objective: To assess in a single study the individual and treatment characteristics that influence the pharmacokinetics and pharmacodynamics of natalizumab in multiple sclerosis (MS) patients in the real-world practice.Methods: Prospective observational study to analyse the impact of body weight, height, body surface area, body mass index, gender, age, treatment duration, and dosage scheme on natalizumab concentrations and the occupancy of α4-integrin receptor (RO) by natalizumab.Results: Natalizumab concentrations ranged from 0.72 to 67 μg/ml, and RO from 26 to 100%. Body mass index inversely associated with natalizumab concentration (beta = −1.78; p ≤ 0.001), as it did body weight (beta = −0.34; p = 0.001), but not height, body surface area, age or gender Extended vs. standard dose scheme, but not treatment duration, was inversely associated with natalizumab concentration (beta = −7.92; p = 0.016). Similar to natalizumab concentration, body mass index (beta = −1.39; p = 0.001) and weight (beta = −0.31; p = 0.001) inversely impacted RO. Finally, there was a strong direct linear correlation between serum concentrations and RO until 9 μg/ml (rho = 0.71; p = 0.003). Nevertheless, most patients had higher concentrations of natalizumab resulting in the saturation of the integrin.Conclusions: Body mass index and dosing interval are the main variables found to influence the pharmacology of natalizumab. Plasma concentration of natalizumab and/or RO are wide variable among patients and should be routinely measured to personalize treatment and, therefore, avoid either over and underdosing.

Introduction In the last few years, a new T cell therapy, chimeric antigen receptor-T (CAR-T) cells, has been developed. CAR-T cells are highly effective at inhibiting antitumor activity, but they can cause a wide spectrum of unusual side effects. Areas covered The present review provides an overview of the adverse events of CAR-T cell therapy, focusing on cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, increased risk of infections, and other long-term complications. Representative studies addressing the safety and efficacy of CAR-T cell therapy are summarized. Expert opinion In the coming years, we predict a great expansion in the use of CAR-T cell therapy with it applied to a higher number of patients with both malignant neoplasms and immune-mediated diseases. Despite physicians and patient expectations about the potential of this therapy, there are still several barriers that may limit providers' ability to supply quality care. This exciting and powerful new therapy requires the formation of new multidisciplinary teams to carry out a safe treatment administration and to successfully manage the resultant complications. The follow-up of these therapies is important for two aspects: effectiveness in different populations and real-life safety in short and in long-term follow-up.

Inflammation is a biological response of the immune system to harmful stimuli. Importantly, inflammation is also a hallmark of several human diseases such as cancer or diabetes. Novel drugs to treat this response are constantly researched, but the formulation is usually forgotten. Cyclodextrins (CDs) are a well-known excipient for complexing and drug delivery. Anti-inflammatory drugs and bioactive compounds with similar activities have been favored from these CD processes. CDs also illustrate anti-inflammatory activity per se. This review tried to describe the capacities of CDs in this field, and is divided into two parts: Firstly, a short description of the inflammation disease (causes, symptoms, treatment) is explained; secondly, the effects of different CDs alone or forming inclusion complexes with drugs or bioactive compounds are discussed.

The discovery of antifibrotic agents have resulted in advances in the therapeutic management of idiopathic pulmonary fibrosis (IPF). Currently, nintedanib and pirfenidone have become the basis of IPF therapy based on the results of large randomized clinical trials showing their safety and efficacy in reducing disease advancement. However, the goal of completely halting disease progress has not been reached yet. Administering nintedanib with add-on pirfenidone is supposed to enhance the therapeutic benefit by simultaneously acting on two different pathogenic pathways. All this becomes more important in the context of the ongoing global pandemic of coronavirus disease 2019 (COVID-19) because of the fibrotic consequences following SARS-CoV-2 infection in some patients. However, little information is available about their drug–drug interaction, which is important mainly in polymedicated patients. The aim of this review is to describe the current management of progressive fibrosing interstitial lung diseases (PF-ILDs) in general and of IPF in particular, focusing on the pharmacokinetic drug-drug interactions between these two drugs and their relationship with other medications in patients with IPF.

Resumen La ruta de senalizacion de las proteinas de la familia Janus cinasa (JAK) esta implicada en la patogenia de muchas enfermedades inflamatorias y autoinmunitarias, como la artritis reumatoide (AR), la psoriasis y la enfermedad inflamatoria intestinal. Una gran cantidad de citocinas implicadas en el desarrollo de estas enfermedades utilizan esta via de senalizacion para transducir senales intracelulares. En los ultimos anos, la aparicion de los inhibidores de las proteinas JAK (jakinibs) ha demostrado que los farmacos relacionados con esta ruta patogenica pueden tener gran aplicabilidad clinica. Tofacitinib y baricitinib, primeros jakinibs aprobados para el tratamiento de la AR, estan en estudio para el tratamiento de otras enfermedades autoinmunitarias. Asimismo, otros jakinibs se encuentran en diferentes fases de desarrollo. En este trabajo se revisan los principales aspectos en cuanto a eficacia, interacciones farmacologicas y seguridad tanto de los jakinibs clasicos como de los de nueva generacion.

Queued Radio Frequency Identification (RFID) networks arise naturally in many applications, where tags are grouped into batches, and each batch must be processed before the next reading job starts. In these cases, the system must be able to handle all incoming jobs, keeping the queue backlogs bounded. This property is called stability. Besides, in RFID networks, it is common that some readers cannot operate at the same time, due to mutual interferences. This fact reduces the maximum traffic that readers can process since they have to share the channel. Synchronous networks share the channel using a TDMA approach. The goal of this work is to analytically determine whether a synchronous queued RFID network attains stable operation under a given incoming traffic. Stability depends on the service rate, which is characterized in this paper using an exact numerical method based on a recursive analytical approach, overcoming the limitations of previous works, which were based on simplifications. We also address different flow optimization problems, such as computing the maximum joint traffic that a network can process stably, selecting the minimal number of readers to process a given total load, or determining the optimal timeslot duration, which are novel in the RFID literature. Ministerio de Economía, Industria y Competitividad | Ref. TEC2016-76465-C2-1-R

IntroductionRecent studies explored promising new quantitative methods to analyze electroencephalography (EEG) signals. This paper analyzes the correlation of two EEG parameters, Brain Symmetry Index (BSI) and Laterality Coefficient (LC), with established functional scales for the stroke assessment.MethodsThirty-two healthy subjects and thirty-six stroke patients with upper extremity hemiparesis were recruited for this study. The stroke patients where subdivided in three groups according to the stroke location: Cortical, Subcortical, and Cortical + Subcortical. The participants performed assessment visits to record the EEG in the resting state and perform functional tests using rehabilitation scales. Then, stroke patients performed 25 sessions using a motor-imagery based Brain Computer Interface system (BCI). BSI was calculated with the EEG data in resting state and LC was calculated with the Event-Related Synchronization maps.ResultsThe results of this study demonstrated significant differences in the BSI between the healthy group and Subcortical group (P = 0.001), and also between the healthy and Cortical+Subcortical group (P = 0.019). No significant differences were found between the healthy group and the Cortical group (P = 0.505). Furthermore, the BSI analysis in the healthy group based on gender showed statistical differences (P = 0.027). In the stroke group, the correlation between the BSI and the functional state of the upper extremity assessed by Fugl-Meyer Assessment (FMA) was also significant, ρ = −0.430 and P = 0.046. The correlation between the BSI and the FMA-Lower extremity was not significant (ρ = −0.063, P = 0.852). Similarly, the LC calculated in the alpha band has significative correlation with FMA of upper extremity (ρ = −0.623 and P < 0.001) and FMA of lower extremity (ρ = −0.509 and P = 0.026). Other important significant correlations between LC and functional scales were observed. In addition, the patients showed an improvement in the FMA-upper extremity after the BCI therapy (ΔFMA = 1 median [IQR: 0–8], P = 0.002).ConclusionThe quantitative EEG tools used here may help support our understanding of stroke and how the brain changes during rehabilitation therapy. These tools can help identify changes in EEG biomarkers and parameters during therapy that might lead to improved therapy methods and functional prognoses.

This paper presents an orchestration framework for the delivery of 5G vertical services and end-to-end network slices in a multi-domain scenario. The proposed architecture relies on a business model where verticals and service providers take the roles of digital service consumers, digital service providers and network service providers, each acting in its administrative domain. The interactions and delivery procedures among these entities leverage on standard solutions for interfaces and information models defined by ETSI and 3GPP. The paper also presents proof-of-concept applications of the proposed architecture in two H2020 European research initiatives.

Radio Frequency Identification (RFID) is considered one of the pioneering technologies of the Internet of Things (IoT). It allows to bind physical environments to information processing systems, adding new capabilities like automatic inventorying, location, or sensing with batteryless tags. Indeed, many data flows of physical objects can be tracked using this technology, and it is common to find heterogeneous traffics present in the same facility, each managed by different sets of readers. For example, in a grocery store, typically we have two kinds of readers: those carrying out a continuous inventory, whose goal is knowing the contents of the shelves as accurately as possible, and a set of checking-out readers at exit gates for the billing process that has to minimize the waiting time of customers. Another example of multiclass traffic is a hospital, where new families of sensing tags allow staff to wirelessly monitor patients&mdash, which obviously must be done as a priority&mdash, and coexist with other readers aimed at precisely knowing the location of equipment or drugs. Even with the same goal, there could be readers requiring different setups, for example in the hospital case, readers located at doors for inventorying purposes have a short time available to identify passing-by objects or people, and thus they have to work with a higher priority than regular readers performing inventorying tasks. In this work, we investigate a modification of the standard listen-before-talk (LBT) protocol for RFID networks which can support this kind of multipriority environment, by offering different qualities of service to each traffic. Results demonstrate that by tuning the protocol setup, it is possible to establish a trade-off between the performance of each traffic. This is shown for the two cited examples, the grocery shop and the hospital, using a simulation tool allowing us to implement a full-scale RFID model. In addition, we present a greedy mechanism for online reader setup. Instead of selecting offline a hard priority level, this greedy algorithm is able to adapt the priority to achieve the required quality-of-service (QoS) level.

Despite being saturated, a huge quantity of “novel” functional food products reaches the food market every day and companies are looking for new products to catch consumers’ attention. In the present study, the inclusion complexes of oxyresveratrol with α-, β- and γ-CD are characterized using DSC, TGA, SEM and molecular docking and their complexing capacities arecompared. As β-CD showed the best results, i) 0.2 mM oxyresveratrol alone, ii) 0.2 mM oxyresveratrol complexed with 8 mM β-CD and iii) 4 mM oxyresveratrol solubilized with 8 mM β-CD were used to fortify, juice and milk food models, and kept in typical storage conditions (darkness and/or refrigerated) conditions for one month. The results showed that CD supplementation leads to a higher oxyresveratrol concentration and antioxidant capacity than when not used. Oxyresveratrol/β-CD food models were stable for five weeks. The most typical variables measured were compared. In vitro digestion pointed to similar bioaccessibility. The bacteriostatic effect was also studied and the greater effectiveness of oversaturated solutions was demostrated. These results should be useful for the food industry for designing hydrophilic products containing oxyresveratrol.

There is a significant lack of software firewalls for 5G networks especially when the support for the Internet of Things (IoT) technologies such NB-IoT are considered. The main contribution of this research work is an advanced software firewall based on the Open Virtual Switch (OVS), which is able to provide firewall capabilities over these 5G IoT devices. The proposed software firewall is able to significantly scale up the number of rules to fulfill the 5G Key Performance Indicator of controlling 1 million IoT devices per square kilometer. Intensive experimental results are achieved in this work, validating the suitability of the proposed architecture for this remarkable level of scalability. In the most demanding conditions, where more than 1 million of firewall rules are installed and 1 million NB-IoT devices are sending traffic, yielding a total of 4 Gbps, the system shows only 8% of packet loss and 4 ms delay.

Background The food industry is constantly attempting to develop better products that will have a positive effect on health (commonly known as functional foods). In this respect, cyclodextrins (CDs) could be of interest because they are tasteless, non-caloric and odourless molecules with several valuable characteristics, such as a capacity to separate chiral compounds and solubilize or stabilize bioactive compounds (BaC). Scope and approach This review represents a revision of the state-of-the-art of CDs and their uses in the food industry. Key findings and conclusions We analysed their metabolism and regulatory aspects of current applications of CDs: as carriers, for removing components, to produce or extract BaC, their use as nanosensors or in food packaging. We study how inclusion complexed are formed referring to the most common techniques and parameters Moreover, how inclusion complexes are formed will be studied with reference to the most common techniques and parameters. In conclusion, their applications in the food and other industries will increase in the coming years without a doubt.

Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI, This study was funded in part by the project Discovery, Validation and Implementation of Biomarkers for Precision Oncology [PIE15/00068], and the project FIS PI17/01865 from the Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, awarded to RC, and the projects [JR 17/00007 and PI17/008], awarded to NRL.

Resumen Las interacciones farmacologicas de los agentes biologicos no son bien conocidas. Debido a que los farmacos biologicos no son metabolizados por las enzimas del citocromo P450 (CYP450) ni interaccionan con los transportadores transmembrana, existe la percepcion de que estos no presentan interacciones medicamentosas con los farmacos de sintesis quimica. Sin embargo, el aclaramiento de los agentes biologicos puede variar en funcion de la respuesta inmune o si se modifica la expresion de sus celulas diana, lo cual puede ocurrir por la accion de muchos agentes quimicos. Ademas, algunos biologicos son capaces de modular la expresion de las enzimas del sistema CYP450. En esta revision, se proporciona una descripcion de las propiedades farmacocineticas y posibles interacciones de los farmacos biologicos, centrandonos en los anticuerpos monoclonales, y como estos pueden interaccionar con las moleculas de sintesis quimica. Creemos que su conocimiento es importante para los clinicos y afecta a varias especialidades medicas.

The pharmacological interactions of biological agents are not well known. Because biologic agents are not metabolised by cytochrome P450 (CYP) enzymes and do not interact with cell membrane transporters, it is generally perceived that they are free from interactions with small molecule drugs. However, the clearance of biological agents varies depending on the modulation of the immune response or by either increasing or reducing the expression of target cells of the biological agents, which can occur through the action of multiple synthetic chemical agents. Furthermore, some biological agents may modify the metabolism of chemical drugs through their effects on the expression of P450 system enzymes.. In this review, we will provide an outline of the pharmacokinetics properties and pharmacologic interactions of biological drugs, focusing on monoclonal antibodies, and how these can interact with chemical synthesis molecules. We believe knowledge of them is important for clinicians and affects multiple clinical specialties.

This review brings together publications in the form of articles, reports, theses and patents related to the use of solid oxide fuel cells in aircraft with a focus on replacing the current auxiliary units with a hybrid system. The potential advantages and main challenges of the new technology are reported, indicating some possible trends in this technology. However, even after many studies, some initial challenges remain. For example, the hybrid system did not achieve the necessary weight-efficiency-ratio, and there seems to be no consensus on the choice of the best fuel. We conclude that the most viable short-term applications appear to be unmanned units, particularly because of security issues and low technology maturity. Smaller power applications, in which the new system is responsible for peripheral services such as a power supply for air conditioning, toilets, and heating up food, are candidates to enter the market in the short or medium term. In the long term, applications for fully electric aircraft and clean fuels will certainly be the focus of larger aircraft manufacturers.

There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events.

Ubiquitous applications rely on the data available from sources of different nature and its collection requires careful planning to take into account their availability and accuracy. One of the base technologies of IoT and ubiquitous applications are RFID. Indeed, many data flows of physical objects can be tracked using this technology, and it is common to find heterogeneous traffics present in the same facility, each managed by different sets of readers. For example, we focus on the example of a grocery store, with two kinds of readers: (i) those for carrying out a continuous inventory process, which goal is knowing the contents of the shelves as accurately as possible, and (ii) a set of checking out readers at exit gates for the billing process that has to minimize the waiting time of customers. In this work we investigate a modification of the standard LBT protocol for RFID networks which can support this kind of multi-priority environments, by offering different qualities of service to each traffic. Results demonstrate that by tuning the protocol setup it is possible to establish a trade-off between the performance of either traffic.

RFID networks are subject to interferences caused by simultaneous readers’ operation, and different arbitration mechanisms have been proposed to deal with this issue. If the network is synchronized, it is possible to implement schedulers which decide, at each particular timeslot, which set of readers operates, thus reducing or eliminating interferences. In this paper, we analyze the performance of an optimal scheduler, which controls the transmission power in the RFID cells using a policy which is randomized and stationary, and which aims at maximizing the joint incoming traffic for a given set of readers subject to attain a stable network operation. We have studied two families of policies: (i) the on/off power policy where all active readers operate with the same transmission power, and (ii) an independent power policy where the transmission powers can be different. Additionally, we have compared the performance against a purely on/off policy where readers use a nominal transmission power of 1 W. Results highlight that on/off power policies are only marginally worse than independent power policies, despite the higher flexibility of the latter ones. Thus, a network designer may rely on/off policies. Finally, we have also shown that arbitration mechanisms between readers are required even for networks operating with the DRE masking mode.

This study discusses the solid oxide fuel cell (SOFC) technology paths in the United States and Japan under the national innovation system (NIS) framework using the available literature and a patent landscape. By examining technology trajectories, it is possible to identify and justify the patterns of key players and institutions from the NISs of the two countries that shaped the development of these technologies. These patterns are especially relevant to the analysis of the role of institutional arrangements in policymaking. This study presents the concept of a NIS and explores the main aspects of the Japanese and U.S. NISs regarding the SOFC technology path. This study analyzes historical patent evolution, patent applicants and their industrial sectors, international patent classifications (IPCs) and international patent activity. Moreover, this study highlights the correlations of the SOFC manufacturing and operation with patent data. This study examines the role of NISs in SOFC technology shaping from two main aspects: through independent historical events that motivated the establishment of institutional arrangements from which SOFCs have benefited and through shaping policies and efforts that are intended to promote the development of SOFC and related technologies. The results of this study demonstrate differences in terms of the sectors that are involved in the SOFC patenting activity, the IPCs of the filed patents and the international patent activity, which support the role of NISs in technology shaping.

Niemann Pick disease Type C (NPC) is a recessive rare disease caused by the mutation on NPC1 and/or NPC2 genes changing the processing of the Low-density proteins (LDL) resulting in an accumulation of lipids in the cells. Until today there is not a cure, the current treatment is based on palliative affairs to reduce the symptoms and prevent its appearance. Among all the treatments proposed the use of cyclodextrins (CDs), nanocarriers which can complex cholesterol, is one of the most useful alternatives. Indeed, for several years 2-hydroxypropyl-β-CD (HPβ-CD) is approved as orphan drug for FDA and EMA to the treatment. However, different CDs based materials are created each year to improve the cholesterol uptake. This review is focused on the novelty of CD based materials for NPC treatment.

Radiofrequency Identification (RFID) installations with passive tags pose the interference problem among readers. Tags require a minimal power-up signal strength sent by the reader to operate and therefore the system is very sensitive to interferences. To face this issue, two mechanisms are used: (a) an anti-collision protocol, which serves to solve tags’ collisions, and (b) a network coordination protocol, which coordinates readers operation to avoid them transmitting at the same time (and thus interfering each other).In this paper we address a thorough study of the standardized coordination protocol Listen Before Talk (LBT), which has been issued by the European regulation ETSI 302 208. The goal is describing the network operation in terms of the achievable throughput, by carefully detailing all the critical settings of a real facility: (a) a physical model for the channel which involves precise computations of powers and gains, sensitivities and channel fading, (b) modeling the anti-collision mechanism ISO 18000-6C (Framed Slotted Aloha), (c) precise operation of the LBT according to the ETSI regulation, (d) realistic traffic modeling (batch works), and (e) accurately computing the precise operation among readers.A variety of results is provided, which are mainly in these categories: throughput versus traffic, versus cell layout, versus network layout, versus reader and anti-collision protocol setup. They can be employed by practitioners in real-world application to understand the performance of RFID networks.

The Janus kinase (JAK) pathway is implicated in the pathogenesis of many inflammatory and autoimmune diseases including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. There are a lot of proinflammatory cytokines involved in such diseases using this pathway to transduce intracellular signals. In the last years, JAK inhibitors (jakinibs) have appeared with a great success, showing that these kinds of drugs have a great applicability in clinical practice. Tofacitinib and baricitinib, the first jakinibs approved for the treatment of RA, are being investigated also for treating other autoimmune systemic diseases. Likewise, other jakinibs are in several phases of development. This review analyses the safety and clinical efficacy of the jakinibs, starting with the classics and continuing with next-generation jakinibs.

Introduction: Adult onset Still's disease (AOSD) is an uncommon systemic inflammatory disease on the clinical spectrum of autoinflammatory disorders. Its presentation and clinical course may result in several well-differentiated phenotypes: from a systemic and highly symptomatic pattern to a chronic articular pattern. Overproduction of numerous pro-inflammatory cytokines is observed in AOSD. Anakinra (ANK), a human interleukin (IL)-1R antagonist, has recently been approved in the EU for the treatment of AOSD. Areas covered: In this review, we discuss the main studies on the efficacy and safety on ANK for the treatment of AOSD. The vast majority of them are retrospective studies and case series. Expert commentary: Overall, ANK is an effective biologic agent for the treatment of AOSD, especially for the systemic pattern and also for those patients who have life-threatening complications, which frequently occur over the course of the disease. The initial dose usually indicated of ANK in adults is 100 mg/day subcutaneously, although dose reduction can be performed in some cases once the disease is under control. The safety profile of ANK is favorable and similar to that described in other rheumatic diseases. In conclusion, ANK is an effective and safe agent for the treatment of AOSD.

This paper introduces a smart assistant for professional volleyball training based on machine-learning techniques (SAETA). SAETA addresses two main aspects of elite sports coaching: 1) technical-tactical effort control, which aims at controlling exercise effort and fatigue levels and 2) exercise quality training, which complements the former by analyzing the execution of player movements. SAETA relies on a sensing infrastructure that monitors both players and their environment, and produces real-time data that is analyzed by different modules of a decision engine. Technical-tactical effort control is based on a dynamic programming model, which selects the best activity and rest durations in interval training, with the goal of maximizing effort while preventing fatigue. Exercise quality control consists of two stages. In the first stage, movements are detected by means of a $k$ -nearest neighbors classifier and in the second stage, movement intensity is classified according to recent statistical data from the player being analyzed. These analyses are reported to coaches and players in real-time. SAETA has been developed in close collaboration with the Universidad Catolica San Antonio de Murcia volleyball team, which competes in the Spanish women’s premier league. Data gathered during training sessions has provided a knowledge base for the algorithms developed, and has been used for the validation of results.

Background Recent times have witnessed a significant increase in the number of patients affected by problems related to oncological treatment Aims of this study is to evaluate dental affectation among patients awaiting hematopoietic progenitor cell transplant (HPCT), and they showed high caries risk, so it should establish a protocol prior to transplantation. Material and methods The study included 72 patients due for HPCT. Clinical and radiological explorations were performed and oral photos taken. The amount of caries, missing teeth and fillings were registered for each patient. CAO, DMFS and Restoration Indices were calculated. Results 83% of patients presented caries. 48 patients (67%) had lost at least one tooth. Only 32 patients (44%) had received some sort of conservative treatment. The average CAO index value obtained was 10.37. The DMFS index showed an average of 27.06 affected surfaces. Of the 72 patients studied, 40 (56%) showed a restoration index value of zero. Conclusions These patients presented a high number of carious teeth and a low restoration index. The presence of so many possible septic foci in an individual, who will later become susceptible to infection, highlights the importance of preventative treatment and bucco-dental restoration within this patient population. These patients with a high caries risk can be treated with CAMBRA system. Key words:Hematopoietic progenitor cell transplantation, high caries risk, state of oral health, haematological disease, CAMBRA system.

In this work, we propose ANT, a network of agents which exchange information in a stigmergy-based fashion. In ANT, each system’s actor distributes pheromones as a way of indicating places’ attractiveness, as well as for building a proper routing path to those sites. The goal of ANT is to improve the chances of discovering points of interest, as well as to reduce the time required for doing so. We have applied ANT to a tourist mobility scenario, where both people and things (events, restaurants, performances, etc.) participate. ANT has achieved notable success in this example case. We find that probability of discovering temporary events and dates improves by more than 35%, while the mean time employed to determine static point decreases by more than a third. We also introduce a mobile-based architecture which performs ANT tasks efficiently and easily for the user. This research has been supported by the project AIM, ref. TEC2016-76465-C2-1-R (AEI/FEDER, EU).

Leukaemia represents 30–40% of all paediatric malignant tumours and is the main cause of death in patients aged

Wireless sensor networks (WSNs) can gather in situ real data measurements and work unattended for long periods, even in remote, rough places. A critical aspect of WSN design is node placement, as this determines sensing capacities, network connectivity, network lifetime and, in short, the whole operational capabilities of the WSN. This paper proposes and studies a new node placement algorithm that focus on these aspects. As a motivating example, we consider a network designed to describe the distribution of helium-3 (3He), a potential enabling element for fusion reactors, on the Moon. 3He is abundant on the Moon’s surface, and knowledge of its distribution is essential for future harvesting purposes. Previous data are inconclusive, and there is general agreement that on-site measurements, obtained over a long time period, are necessary to better understand the mechanisms involved in the distribution of this element on the Moon. Although a mission of this type is extremely complex, it allows us to illustrate the main challenges involved in a multi-objective WSN placement problem, i.e., selection of optimal observation sites and maximization of the lifetime of the network. To tackle optimization, we use a recent adaptation of the ant colony optimization (ACOR) metaheuristic, extended to continuous domains. Solutions are provided in the form of a Pareto frontier that shows the optimal equilibria. Moreover, we compared our scheme with the four-directional placement (FDP) heuristic, which was outperformed in all cases.

Three compounds have been synthesized with formulae [3-MeRad][Ni(dmit)2] (1), [4-MeRad][Ni(dmit)2] (2) and [4-PrRad][Ni(dmit)2] (3) where [Ni(dmit)2]- is an anionic pi-radical (dmit = 1,3-dithiol-2-thione-4,5-dithiolate) and [3-MeRad]+ is 3-N-methylpyridinium alpha-nitronyl nitroxide, [4-MeRad]+ is 4-N-methylpyridinium alpha-nitronyl nitroxide and [4-PrRad]+ is 4-N-propylpyridinium alpha-nitronyl nitroxide. The temperature-dependent magnetic susceptibility of 1 revealed that an antiferromagnetic interaction operates between the 3-MeRad+ radical cations with exchange coupling constants of J1 = - 1.72 cm-1 and antiferromagnetism assigned to the spin ladder chains of the Ni(dmit)2 radical anions. Compound 1 exhibits semiconducting behavior and 3 presents capacitor behavior in the temperature range studied (4 - 300 K).

A small-scale, single operation, dry degerminator, originating from Brazil was tested on six maize samples (from France and Mali) at two moisture contents (10 and 15% wb). The yield of brewery maize grits (< 1% lipids) was higher for extensively dry (10% me) and hard grains. It ranged from 50 to 70% for four cultivars, which was equivalent or higher than for industrial plants. The rancidity of the products was controlled by the fat acidity level, which was 40?60 mg KOH 100 g?1db, after 4 months storage of degermed flour. This indicates that degermed products can be stored at 35°C for up to 6 months without developing significant rancid off?flavour. Thus the Brazilian dry degerminator appears suitable for the treatment of maize in the tropical zone of Africa. (Resume d'auteur)

This paper presents a novel system for effort control in team-sport training, where each component is associated with a particularized program. The system relies on a decision engine that analyzes training data and provides instructions to athletes, and on a sensing infrastructure which monitors athletes' biometrics and movements and gathers environmental data such as humidity or temperature. The prototype has been developed using IMOTE2 and MicaZ sensors under TinyOS and BioHarness biometric belts. The decision technique estimates the ratios of each effort regime, based on best-fit polynomial approximations using historical data from previous training sessions. The complete system results in a virtual coach, operating in real time and automatically. This methodology has been piloted in an experiment with the UCAM Volleyball Murcia team, top of the Spanish national women's volleyball league. Data obtained during training sessions have provided a knowledge base for the algorithms developed and allowed for validation of the results.

Background The outpatient pharmacy unit (OPU), in consensus with the digestive service (DIG), held an intervention on selected chronic hepatitis B virus (HBV) infected outpatients. It consisted of decreasing the frequency of oral treatment from a monthly to a bimonthly basis. The aim was to reduce patient visits to the hospital and to diminish the healthcare burden in order to use human resources to improve pharmaceutical care. Purpose To evaluate the impact on adherence and viral load (VL) after dispensing treatment on a bimonthly basis instead of a monthly basis to selected HBV outpatients. Material and methods In May 2014, patients were transversely selected by OPU following the criteria reached by consensus with DIG: age >18 years, receiving any oral drug (alone or combined) for HBV infection, HBV VL ≤100 copies/mL in their last analysis, on stable treatment for at least 6 months previous to the study and related adherence throughout that period >80%. All selected patients were informed about the importance of adherence, and bimonthly dispensation was offered to them. The next set of data was collected from the medical records: sex, age and VL. Adherence was measured by indirect methods from the dispensation programme registry (Farmatools). In May 2015, adherence since the intervention and VL values were revised for the selected patients to evaluate the effect of the intervention. Results 94 patients met the criteria but only 73 wanted to change to bimonthly dispensation: 56.15% male, median (P50) age 52 (44–61). Results refer to 63 patients, as 8 patients had no analysis after the intervention and 2 were lost to follow-up. After the intervention, 6 patients still met the criteria. 35 patients maintained the same VL and 17 had decreased VL (13 to undetectable). 9 had increased VL but still met the criteria and 8 of them had adherence variation Conclusion Bimonthly dispensation is a safe tool for maintaining stable adherence and VL in selected patients and could be used to rationalise the use of the limited human resources of pharmacy services and reduce patient visits to hospital. References and/or Acknowledgements Ibarra O. Adherencia al tratamiento VHB. Grupo Hepatopatias Viricas. SEFH.2 junio 2010. Barcelona No conflict of interest.

Background Natalizumab is approved for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) who have failed firstline treatment or who have highly active disease. The drug has proved highly effective. However, it has been associated with a risk of progressive multifocal leukoencephalopathy (PML). Purpose To evaluate natalizumab maintenance in our centre and the motives for suspension. Material and methods Retrospective observational study of RRMS patients treated with natalizumab in the past 5 years in our hospital. Collected data were: age, gender, diagnosis, previous treatments, Expanded Disability Status Scale (EDSS), length of treatment, Ac JCV, adverse reactions, and reasons for beginning and suspending treatment. Results We analysed 36 patients: 22 women and 14 men. Mean (SD) age of patients: 39.1 (59) years. 12 (33.3%) patients had 2 or more previous medications, 20 (55,5%) had 1 previous medication and 4 (11.1%) had no previous medication. Previous treatment was interferon beta in 16 patients (44.4%), glatiramero in 14 (38,8%) and fingolimod and teriflunomida in 1 patient (2.7%) each. The reasons for starting natalizumab therapy were treatment failure in 27 patients (75%), aggressive disease start in 4 patients (11.1%) and other reasons in 5 patients (13.8%). 20 patients (55.5%) were seropositive to JVC (index value ranged from 0.02 to 3.7), of whom 3 suffered positive seroconversion. Mean (SD) EDSS score was 2.9 (2.04). 6 patients (16.6%) had hypersensitivity reactions, with positive natalizumab antibodies in 2 patients.13 (36.1%) had perfusion reactions. Median duration of treatment was 26 months. 2 patients (5.5%) had progressed in the disease. The main reasons for suspending therapy were risk of developing PML in 9 patients (25%), treatment failure in 4 patients (11.1%), the patient’s wish in 3 (8.3%) cases and other reasons in 2 (5.5%) patients. There were no PML events. Conclusion The average duration of maintenance of treatment with natalizumab was 26 months; the principal motive for suspension was the risk of PML. Effective scoreboards for PML risk are important and necessary to identify patients at greatest risk, and to be able to minimise the risk. References and/or Acknowledgements EMA data sheet Hospital La Princesa Clinical Histories No conflict of interest.

Los requerimientos de ácidos grasos esenciales (AGEs) y ácidos grasos poliinsaturados de cadena larga (AGPI-CL) durante los últimos meses de gestación y los primeros años de vida son importantes de acuerdo al crecimiento y desarrollo neuronal que está teniendo lugar durante este periodo de vida. El objetivo de este trabajo ha sido destacar la importancia de garantizar un correcta ingesta de AGEs para cubrir los requerimientos nutricionales de estos, a través de la ingesta de alimentos que contienen en su composición nutricional a estos ácidos de forma natural o han sido enriquecidos con ellos. La metodología empleada para este fin ha sido la utilización de bases de datos electrónicas como MedLine, ScienceDirect, Scirus, Trip database y de la hemeroteca científica de la Universidad de Murcia; También han sido consultadas las páginas web de organismos nacionales e internacionales tales como la Asociación Española de Pediatría (AEP), Agencia Europea de Seguridad Alimentaria (EFSA) y European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN). Los resultados obtenidos muestran como los AGEs e incluso los AGPI-CL (DHA y ARA) son esenciales para el correcto desarrollo del lactante y niño de corta edad; pues aún estando el lactante desde el primer día de vida dotado de todo el sistema enzimático necesario para la conversión de AGEs en sus correspondientes AGPI-CL y sus derivados, esta conversión podría ser insuficiente, siendo necesario y/o esencial el aporte de estos AGPI-CL a través de la dieta. Las conclusiones derivadas de este trabajo fueron que durante los seis primeros meses de vida el aporte de AGEs y AGPI-CL está asegurado a través de la leche materna o en su defecto a través de las fórmulas de inicio; a partir de los 6 meses con la introducción de la alimentación complementaria y la introducción de la leche de vaca a partir de los 12 meses de vida (introducción en contra de las recomendaciones de ESPGHAN), podría verse comprometida la aportación de estos ácidos. Existe un vacío legal en cuanto a la aportación de AGEs a través de la alimentación complementaria distinta a los cereales; sin embargo, comités como el de la AEP recomienda que en los tarritos infantiles de carnes y pescados con verdura, el aporte de AL sea entre 3-4.5% de la energía de la dieta y al menos 0.5% desde ALN para satisfacer los requerimientos de AGEs en lactantes y niños de corta edad. Essential fatty acids and long-chain unsaturated fatty acids are important for growth and neuronal development during the final months of gestation and the early years of life. The aim of this study is to highlight the importance of ensuring a correct intake of EFAs for nutritional requirements through the intake of foods which naturally contain these acids or which have been enriched with them. The methodology used was basee on the review of electronic databases MedLine, ScienceDirect, Scirus, Trip database and that of the scientific journal library of the University of Murcia. National and international websites such as the Asociación Española de Pediatría (AEP), European Agency for Food Safety (EAFS) and the European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN) were also consulted. The results show how EFAs and also AGPI-CL (DHA and ARA) are essential for the correct development of breastfeeders and infants. Even though the breastfeeder is enzymatically fully equipped from the first day of life to convert EFAs into AGPI-CL and derivatives, the conversion may be insufficient and it may be necessary to include AGPI-CL in the diet. The conclusions are that during the first 6 months of life the provision of EFAs and AGPI-CL is assured thanks to the mother’s milk or through starter formulas; at six months the introduction of complementary foods and the adaptation to cow’s milk at twelve months (against the recommendations of the ESPGHAN) may affect the provision of these acids. There is a legal vacuum in the issue of the provision of EFAs through complementary foods other than cereals although committees like the AEP recommend that AL in meat and fish baby foods with vegetables should suppose 3-4.5% of the energy provision, and ALN at least 0.5% in order to satisfy EFA requirements in breastfeeders ans infants.

Outdoor sport practitioners can improve greatly their performance if they train at the right intensity. Nevertheless, in common training systems, performance is only evaluated at the end of the training session, and sensed data are incomplete because only human biometrics are analyzed. These systems do not consider environmental conditions, which may influence athletes’ performance directly during instruction. In this paper, we introduce a decision making method for a multi-step training scenario based on dynamic program optimization and formulated as a Markov Decision Process, which allow athletes to complete heterogeneous training programs with several levels of exercise intensity. This methodology is applied in a pilot experiment of cross-country running. Environment and athletes are monitored by means of a wireless sensor network deployed over the running circuit, and by mobile elements carried by the users themselves, which monitor their heart rate (HR). The goal is to select, for a given user, a running track that optimizes heart rate according to a predefined training program. Results show that the proposal is of practical interest. It achieves a notable success in heart rate control over non-optimal track selection policies. The importance of environmental data is shown as well, since heart rate control improves when those data are taken into account.

In this paper, we comparatively analyze a set of decision making methodologies that have been successfully applied to improve athletes' training in real-time. The decision-making processes are based on the environmental data as well as on the athletes' biometrics in a scenario with runners in cross country circuits. Data acquisition is performed by means of a WSN which measures temperature and circuits slopes, whereas heart rate is monitored for each athlete. In all cases, the goal was to select the best tracks in the circuit to control the heart rate of the athlete within a given interval. Two broad types of decision-making procedures have been studied: (i) optimal classifiers, and (ii) dynamic programming. Results show a notable performance increase of these methods over heuristics, as well as the importance of environmental sensor data.

Outdoor sport practitioners can improve greatly their results if they train at the right intensity. Nevertheless, in common training systems the athlete's performance is used for evaluation at the end of the exercises, and the sensed data is incomplete because only human biometrics are analyzed. These systems do not consider environmental conditions, which may have direct influence on athlete's performance during training. In this paper, we present the system architecture and implementation of an ambient intelligence assistant for runners. Our system is composed of a Wireless Sensor Network (WSN) deployed over a cross-country running circuit, and by mobile elements carried by the users, which monitor their heart rate (HR). The goal is to select, for a given user, suitable tracks where the heart rate will be in the selected HR range. The decision-taking process is based on k-NN classification and has achieved a success classification ratio of 70%.

Several research programs are tackling the use of Wireless Sensor Networks (WSN) at specific fields, such as e-Health, e-Inclusion or e-Sport. This is the case of the project “Ambient Intelligence Systems Support for Athletes with Specific Profiles”, which intends to assist athletes in their training. In this paper, the main developments and outcomes from this project are described. The architecture of the system comprises a WSN deployed in the training area which provides communication with athletes’ mobile equipments, performs location tasks, and harvests environmental data (wind speed, temperature, etc.). Athletes are equipped with a monitoring unit which obtains data from their training (pulse, speed, etc.). Besides, a decision engine combines these real-time data together with static information about the training field, and from the athlete, to direct athletes’ training to fulfill some specific goal. A prototype is presented in this work for a cross country running scenario, where the objective is to maintain the heart rate (HR) of the runner in a target range. For each track, the environmental conditions (temperature of the next track), the current athlete condition (HR), and the intrinsic difficulty of the track (slopes) influence the performance of the athlete. The decision engine, implemented by means of (m; s)-splines interpolation, estimates the future HR and selects the best track in each fork of the circuit. This method achieves a success ratio in the order of 80%. Indeed, results demonstrate that if environmental information is not take into account to derive training orders, the success ratio is reduced notably. This work has been supported by grants DEP2006-56158-C03-01/02/03, TEC2007-67966 -01/02/TCM CON-PARTE-1/2 (Ministerio de Educacion y Ciencia, Spain), TSI-020301-2008-16 ELISA and TSI-020301-2008-2 PIRAmIDE (Ministerio de Industria, Turismo y Comercio, Spain), and it has been also developed within the framework of “Programa de Ayudas a Grupos de Excelencia de la Region de Murcia”, funded by Fundacion Seneca, Agencia de Ciencia y Tecnologia de la Region de Murcia (Plan Regional de Ciencia y Tecnologia 2007/2010).

Background Strategies to simplify HIV treatment are driven by concerns about the long-term toxicity of chronic combination antiretroviral therapy (ART), cost, and the risk of drug resistance over time due to non-adherence. Ritonavir-boosted protease inhibitors (PIs) can be an alternative. Purpose To assess the effectiveness and safety of ritonavir-boosted PI monotherapy and whether the switching has been done in compliance with European AIDS Clinical Society guidelines. Material and methods A large, retrospective observational, non-interventionist study was carried out including 91 patients on ritonavir-boosted PI monotherapy. Patients were followed since they started ART to December 2013 (the date at which all of the patients had been switched for at least 6 months). Data were collected and summarised in a table with the following characteristics: Date of HIV diagnose, PI/r monotherapy toxicity, Adherence and Date of starting with PI/r monotherapy, viral load at the moment of the simplification, viral load in December 2013. Results 21 out of 91 (23%) patients had detectable HIV-RNA at the moment of the simplification thus they did not meet the guideline recommendations for switching. 15 out of 91 (16%) patients had a detectable viral load on December 2013 thus the switching had failed in them. Patients had fewer episodes of lipodystrophy, only 14 out of 91 (15%), and cardiovascular complications, only 4 out of 91 (4.35%). 84 out of 91 (92%) patients had more than 85% adherence to the treatment. Conclusion The overall effectiveness of ritonavir-boosted protease inhibitor monotherapy is inferior to ART. However 84% of patients have no viral rebound with HIV-RNA levels above 50 copies/ml, which is why there may be a subset of patients with a history of prolonged viral suppression who may benefit from switching to ritonavir-boosted protease inhibitor (PI) monotherapy to reduce adverse reactions and costs, and achieve more adherence. References and/or acknowledgements Hospital de La Princesa Team No conflict of interest.

Background In 2005, the Safe Use of Drug and Health Products website was launched by the Health Department of the Madrid Autonomous Community. Any health professional can communicate drug prescription errors detected through Functional Risk Management Units (UFR). Patient safety is a strategic guideline used. Considering that the drug treatment is one of the most widely used health services, and one of the most complex and effective, in terms of technology, attention needs to be given to this point and to its safe use. Purpose To analyse the medicines errors submitted from the Pharmacy Service to the UFR, to identify and prioritise actions for improvement. Materials and methods The submissions made through an online formulary to the Safe Use of Drug and Health Products website were analysed from September 2011 to September 2013. –From all items of the formulary, we collected: error type, patient consequences, stage of the process and place where it happened. –Error notification is anonymous and confidential. Results During the study, 159 errors were reported. Regarding the process stage: 135 (84.9%) during prescription, 13 (8.2%) while dispensing, 3 (1.88%) during manufacture, 3 (1.88%) during administration, 3 (1.88%) during labelling, 1 (0.63%) during validation and 1 (0.63%) during transcription. Concerning the type of error: 54 (33.96%) were due to a dose error, 25 (15.72%) to an administration frequency error, 22 (13.83%) due to a drug selection error, 12 (6.92%) due to a dispensing error, 8 (5%) due to a manufacturing error, 4 (2.5%) due to dispensing to the wrong patient, 3 (1.8%) due to a treatment length error and 3 (1.8%) due to a lack of drug quality. Regarding the consequences for the patient: 70 (44%) didn’t reach the patient; of the 69 (43.3%) events that could have caused an error, 17 (10.7%) reached the patient with no damage, 2 (1.2%) harm was done but was impossible to trace, 1 (1.72%) monitoring was required. Concerning the unit where the error took place: 111 (69.8%) in the hospital plant, 23 (14.5%) in the Pharmacy Service, 18 (11.3%) in the Urgency Service and 8 (5%) in other units. Conclusions Recording and categorising the drug errors provides the most accurate information about which points must be improved regarding the complex process of drug use. A lot of drug errors occur during the prescription but most of them do not reach the patients. The errors prompt us to continue improving the electronic validation of prescriptions, as well as future actions in other areas. No conflict of interest.

Background Breastfeeding is the gold standard of infant feeding, however not all infants with cow’s milk protein allergy (CMPA) tolerate human milk. In these cases, it seems recommended the use of extensively hydrolyzed formula (eHF). Preliminary analyses such as antigenicity and protein quality evaluation are needed to ensure that new formula will be nutritionally suitable, tolerated and safe for infants with CMPA. The aim of this study was to determine the protein quality of a whey hydrolysate (WH) and casein hydrolysate (CH).

Processing conditions for making pasta from blends of maize (Zea mays L) flour and durum wheat (Triticum durum Desf) semolina (ratio 66 : 33w) were studied. The maize mill stream characteristics determined the quality of the maize pasta; flours with low lipid content and very fine granulometry produced pasta with good colour characteristics and high cooking quality (with especially good surface conditions). The use of white maize varieties was preferred; they produced pasta which, after heat treatment, had colour indices close to those of durum wheat pasta. Extrusion conditions affected the colour characteristics and cooking quality of the pasta. The cooking qualities of macaroni products were better than those of spaghetti. In all cases, heat treatment (90¼C for 2 h) improved the cooking quality of the pasta : it reduced cooking losses but did not alter the surface condition and viscoelasticity index