Publications

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Surgical robots are endowed with valuable features that allow surgeons improving their work in terms of accuracy, quality, efficiency and liability. Tremor reduction, scaled movements, virtual fixtures, pre and intraoperative imaging are some examples of enhancing aids for the surgeon. Moreover, being robotics surgery still at an early phase of development, current research efforts are focused to develop robotic systems able to solve more complex tasks, though the associated costs of robotics makes the convenience of its use in some kind of interventions questionable. After analyzing the main performances and limitations of current surgical robots, this paper foresees advances towards ideal robotic systems that satisfy the requirements of future robots.

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One of the main causes of car accidents is drowsiness. There have been many studies regarding driving monitoring systems in the past few years, although most of them are focused in simulator environments. This paper presents a system to detect drowsiness patterns in real driving environments, where many external conditions need to be taken into account. Initial tests were done in simulator, followed by tests in real vehicles. Although two different approaches have been developed, this paper is focused in the inadequate driving identification based on the steering movements. Its sub-modules are also presented, with a special focus on the active driving detector.

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Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis.

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Nanopharmaceutics composed of a carrier and a protein have the potential to improve the activity of therapeutical proteins. Therapy for lysosomal diseases is limited by the lack of effective protein delivery systems that allow the controlled release of specific proteins to the lysosomes. Here we address this problem by developing functional polyelectrolyte-based nanoparticles able to promote acidic pH-triggered release of the loaded protein. Trimethyl chitosan (TMC) was synthesized and allowed to form polyelectrolyte complexes (PECs) with the lysosomal enzyme α-GAL through self-assembly and ionotropic gelation, with average particle size <200 nm, polydispersity index (PDI) <0.2, ζ potential of 20 mV, and a protein loading efficiency close to 65%. These polyelectrolyte nanoparticles were stable and active under physiological conditions and able to release the enzyme at acidic pH, as demonstrated by in situ atomic force microscopy (AFM). These nanoparticles were further functionalized with Atto 647N for single-particle characterization and tracking their cellular uptake and fate using high-resolution fluorescence microscopy. In contrast with their precursor, TMC, PECs were efficiently internalized by human endothelial cells and mostly accumulated in lysosomal compartments. The superior physicochemical characteristics of the TMC/α-GAL PECs together with their excellent cellular uptake properties indicate their enormous potential as advanced protein delivery systems for the treatment of lysosomal storage diseases.

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A first step towards the multidetection, identification and quantification of anabolic androgenic steroids by enzyme-linked immunosorbent assay (ELISA) has been performed in this study. This proposal combines multiple competitive ELISA assays with different cross-reactivity profiles and multivariate data analysis techniques. Data have been analyzed by principal component analysis in conjunction with a novel K-nearest line classifier. This proposal allows simultaneous detection of up to four different steroids in the range of concentration from 0.1 to 316.2 nM with a total rate of 90.6% of correct detection, even in the presence of cross-reactivities. A methodology for concentration prediction is also presented with satisfactory results.

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Coordination of the expression of Salmonella enterica invasion genes on pathogenicity island 1 (SPI1) depends on a complex circuit involving several regulators that converge on expression of the hilA gene, which encodes a transcriptional activator (HilA), that modulates expression of the SPI1 virulence genes. Two of the global regulators influencing hilA expression are the nucleoid associated proteins Hha and H-NS. They interact and form a complex that modulates gene expression. A chromosomal transcriptional fusion was constructed to assess the effect of these modulators on hilA transcription under several environmental conditions as well as at different stages of the growth curve. The results obtained showed that these proteins play a relevant role in silencing hilA expression both at low temperature and low osmolarity, irrespective of the growth phase. H-NS accounts for the main repressory activity. At high temperature and osmolarity H-NS-mediated silencing completely ceases when cells enter the stationary phase, and hilA expression is induced. Mutants lacking IHF did not induce hilA in cells entering the stationary phase, and this lack of induction was dependent on the presence of H-NS. Band shift assays and in vitro transcription data evidence that for hilA induction under certain growth conditions, IHF is required to alleviate H-NS-mediated silencing.

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Biomaterial surface properties, via alterations in the adsorbed protein layer, and the presence of specific functional groups can influence integrin binding specificity, thereby modulating cell adhesion and differentiation processes. The adsorption of fibronectin, a protein directly involved in osteoblast adhesion to the extracellular matrix, has been related to different physical and chemical properties of biomaterial surfaces. This study used blasting particles of different sizes and chemical compositions to evaluate the response of MG63 osteoblast-like cells on smooth and blasted titanium surfaces, with and without fibronectin coatings, by means of real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays. This response included (a) expression of the alpha(5), alpha(v) and alpha(3) integrin subunits, which can bind to fibronectin through the RGD binding site, and (b) expression of alkaline phosphatase (ALP) and osteocalcin (OC) as cell-differentiation markers. ALP activity and synthesis of OC were also tested. Cells on SiC-blasted Ti surfaces expressed higher amounts of the alpha(5) mRNA gene than cells on Al2O3-blasted Ti surfaces. This may be related to the fact that SiC-blasted surfaces adsorbed higher amounts of fibronectin due to their higher surface free energy and therefore provided a higher number of specific cell-binding sites. Fn-coated Ti surfaces decreased alpha(5) mRNA gene expression, by favoring the formation of other integrins involved in adhesion over alpha(5)beta(1). The changes in alpha(5) mRNA expression induced by the presence of fibronectin coatings may moreover influence the osteoblast differentiation pathway, as fibronectin coatings on Ti surfaces also decreased both ALP mRNA expression and ALP activity after 14 and 21 days of cell culture.

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The study of flow cycle morphology provides new information about the breathing pattern. This study proposes the characterization of cycle morphology in chronic heart failure patients (CHF) patients, with periodic (PB) and non-periodic breathing (nPB) patterns, and healthy subjects. Principal component analysis is applied to extract a respiratory cycle model for each time segment defined by a 30-s moving window. To characterize morphology of the model waveform, a number of parameters are extracted whose significance is evaluated in terms of the following three classification problems: CHF patients with either PB or nPB, CHF patients versus healthy subjects, and nPB patients versus healthy subjects. 26 CHF patients (8 with PB and 18 with non-periodic breathing pattern (nPB)) and 35 healthy subjects are studied. The results show that a respiratory cycle compressed in time characterizes PB patients, i.e., shorter inspiratory and expiratory periods, and higher dispersion of the maximum inspiratory and expiratory flow value (accuracy of 87%). The maximal expiratory flow instant occurs earlier in CHF patients than in healthy subjects (accuracy of 87%), with a steeper slope between inspiration and expiration. It is also found that the standard deviation of the expiratory period, evaluated for each subject, is much lower in CHF patients than in healthy subjects. The maximal expiratory flow instant occurs earlier (accuracy of 84%) in nPB patients, when comparing subjects with similar respiratory pattern like nPB patients and healthy subjects.

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One of the most challenging problems in intensive care is the process of discontinuing mechanical ventilation, called weaning process. An unnecessary delay in the discontinuation process and an early weaning trial are undesirable. This paper proposes to analysis the respiratory pattern variability of these patients using autoregressive modeling techniques: autoregressive models (AR), autoregressive moving average models (ARMA), and autoregressive models with exogenous input (ARX). A total of 153 patients on weaning trials from mechanical ventilation were analyzed: 94 patients with successful weaning (group S); 38 patients that failed to maintain spontaneous breathing (group F), and 21 patients who had successful weaning trials, but required reintubation in less than 48 h (group R). The respiratory pattern was characterized by their time series. The results show that significant differences were obtained with parameters as model order and first coefficient of AR model, and final prediction error by ARMA model. An accuracy of 86% (84% sensitivity and 86% specificity) has been obtained when using order model and first coefficient of AR model, and mean of breathing duration.

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The gold standard for diagnosing Sleep Apnea Hypopnea Syndrome (SAHS) is the Polysomnography (PSG), an expensive, labor-intensive and time-consuming procedure. It would be helpful to have a simple screening method that allowed to early determining the severity of a subject prior to his/her enrolment for a PSG. Several differences have been reported in the acoustic snoring characteristics between simple snorers and SAHS patients. Previous studies usually classify snoring subjects into two groups given a threshold of Apnea-Hypoapnea Index (AHI). Recently, Bayes multi-group classification with Gaussian Probability Density Function (PDF) has been proposed, using snore features in combination with apnea-related information. In this work we show that the Bayes classifier with Kernel PDF estimation outperforms the Gaussian approach and allows the classification of SAHS subjects according to their severity, using only the information obtained from snores. This could be the base of a single

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Measurement of upper airway resistance is of interest in sleep disordered breathing to estimate upper airway patency. Resistance is calculated with the airflow and respiratory effort signals. However, there is no consensus on a standard for upper airway resistance measurement. This study proposes a new benchmarking method to objectively compare different upper airway resistance measurement methods by objectively differentiating between breaths with inspiratory flow limitation (high resistance) and non-limited breaths (low resistance). Resistance was measured at peak-Pes, at peak-flow, at the linear portion of a polynomial equation, as an area comparative and as average resistance for an inspiration. A total of 20 patients with systematic, gold-standard esophageal pressure and nasal airflow acquisition were analyzed and 109,955 breaths were automatically extracted and evaluated. Relative resistance values in relationship to a reference resistance value obtained during wakefulness were also analyzed. The peak-Pes measurement method obtained the highest separation index with significant (p < 0.001) differences to the other methods, followed by the area comparative and the peak-flow methods. As expected, average resistances were significantly (p < 0.001) lower for the non-IFL than for the IFL group. Hence, we recommend employing the peak-Pes for accurate upper airway resistance estimation.

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The aim of this study was to evaluate the respiratory muscles efficiency during a progressive incremental flow (IF) respiratory test in healthy and Chronic Obstructive Pulmonary Disease (COPD) subjects. To achieve this, the relationship between mouth Inspiratory Pressure (IP) increment, which is a measure of the force produced by respiratory muscles, and respiratory muscular activity increment, evaluated by means of Mechanomyografic (MMG) signals of the diaphragm muscle, was analyzed. Moreover, the correlation between the respiratory efficiency measure and the obstruction severity of the subjects was also examined. Data from two groups of subjects were analyzed. One group consisted of four female subjects (two healthy subjects and two moderate COPD patients) and the other consisted of ten male subjects (six severe and four very severe COPD patients). All subjects performed an easy IF respiratory test, in which small IP values were reached. We have found that there is an increase of amplitude and a displacement towards low frequencies in the MMG signals when the IP increases. Furthermore, it has also been found that respiratory muscles efficiency is lower when greater the obstructive severity of the patients is, and it is lower in women than in men. These results suggest that the information provided by MMG signals could be used to evaluate the muscular efficiency in healthy and COPD subjects.

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MEET is an R package that integrates a set of algorithms for the detection of transcription factor binding sites (TFBS). The MEET R package includes five motif searching algorithms: MEME/MAST(Multiple Expectation-Maximization for Motif Elicitation), Q-residuals, MDscan (Motif Discovery scan), ITEME (Information Theory Elements for Motif Estimation) and MATCH. In addition MEET allows the user to work with different alignment algorithms: MUSCLE (Multiple Sequence Comparison by Log-Expectation), ClustalW and MEME. The package can work in two modes, training and detection. The training mode allows the user to choose the best parameters of a detector. Once the parameters are chosen, the detection mode allows to analyze a genome looking for binding sites. Both modes can combine the different alignment and detection methods, offering multiple possibilities. Combining the alignments and the detection algorithms makes possible the comparison between detection models at the same level, without having to care about the differences produced during the alignment process. The MEET R package can be downloaded from http://sisbio.recerca.upc.edu/R/MEET_1.0. tar.gz

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Snoring is one of the earliest and most consistent sign of upper airway obstruction leading to Sleep Apnea-Hypopnea Syndrome (SAHS). Several studies on post-apneic snores, snores that are emitted immediately after an apnea, have already proven that this type of snoring is most distinct from that of normal snoring. However, post-apneic snores are more unlikely and sometimes even inexistent in simple snorers and mild SAHS subjects. In this work we address that issue by proposing the study of normal non-regular snores. They correspond to successive snores that are separated by normal breathing cycles. The results obtained establish the feasibility of acoustic parameters of normal non-regular snores as a promising tool for a prompt screening of SAHS severity.

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Autonomic nervous system regulates the behavior of cardiac and respiratory systems. Its assessment during the ventilator weaning can provide information about physio-pathological imbalances. This work proposes a non linear analysis of the complexity of the heart rate variability (HRV) and breathing duration (TTot) applying recurrence plot (RP) and their interaction joint recurrence plot (JRP). A total of 131 patients on weaning trials from mechanical ventilation were analyzed: 92 patients with successful weaning (group S) and 39 patients that failed to maintain spontaneous breathing (group F). The results show that parameters as determinism (DET), average diagonal line length (L), and entropy (ENTR), are statistically significant with RP for TTot series, but not with HRV. When comparing the groups with JRP, all parameters have been relevant. In all cases, mean values of recurrence quantification analysis are higher in the group S than in the group F. The main differences between groups were found on the diagonal and vertical structures of the joint recurrence plot.

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Several studies have shown differences in acoustic snoring characteristics between patients with Sleep Apnea-Hypopnea Syndrome (SAHS) and simple snorers. Usually a few manually isolated snores are analyzed, with an emphasis on postapneic snores in SAHS patients. Automatic analysis of snores can provide objective information over a longer period of sleep. Although some snore detection methods have recently been proposed, they have not yet been applied to full-night analysis devices for screening purposes. We used a new automatic snoring detection and analysis system to monitor snoring during full-night studies to assess whether the acoustic characteristics of snores differ in relation to the Apnea-Hypopnea Index (AHI) and to classify snoring subjects according to their AHI. A complete procedure for device development was designed, using databases with polysomnography (PSG) and snoring signals. This included annotation of many types of episodes by an expert physician: snores, inspiration and exhalation breath sounds, speech and noise artifacts, The AHI of each subject was estimated with classical PSG analysis, as a gold standard. The system was able to correctly classify 77% of subjects in 4 severity levels, based on snoring analysis and sound-based apnea detection. The sensitivity and specificity of the system, to identify healthy subjects from pathologic patients (mild to severe SAHS), were 83% and 100%, respectively. Besides, the Apnea Index (AI) obtained with the system correlated with the obtained by PSG or Respiratory Polygraphy (RP) (r=0.87, p<0.05).

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Innovative Developments in Virtual and Physical Prototyping presents essential research in the area of Virtual and Rapid Prototyping. The volume contains reviewed papers presented at the 5th International Conference on Advanced Research in Virtual and Rapid Prototyping, hosted by the Centre for Rapid and Sustainable Product Development of the Polytechnic Institute of Leiria, Portugal, from September 28 to October 1, 2011. A wide range of topics is covered, such as CAD and 3D Data Acquisition Technologies, Additive and Nano Manufacturing Technologies, Rapid Tooling & Manufacturing, Biomanufacturing, Materials for Advanced Manufacturing Processes, Virtual Environments and Simulation, Applications of Virtual and Physical Prototyping Technologies. Innovative Developments in Virtual and Physical Prototyping is intended for engineers, designers and manufacturers who are active in the areas of mechanical, industrial and biomedical engineering.

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The nanoscale analysis of living cells using atomic force microscopy (AFM)-based techniques is an exciting, rapidly evolving research field. During the past years, there has been tremendous progress in using AFM to observe cell surfaces at high resolution, to study cellular mechanics, to localize cell surface receptors, and to measure the forces involved in cellular interactions. This timely book provides a comprehensive overview of the use of AFM and related scanning probe microscopies for cell surface analysis, from the basics to the applications. The book will appeal to anyone involved in cell biology, microbiology, biophysics, biochemistry, or nanobiosciences. It covers all cell types, from viruses and protoplasts to bacteria and animal cells, and discusses a range of advanced AFM modalities, including high-resolution imaging, nanoindentation measurements, recognition imaging, as well as single-molecule and single-cell force spectroscopy. The different chapters are authored by cutting-edge experts, each representing his or her specialized areas. Each chapter covers methodologies for sample preparation and analysis, and highlights recent examples to illustrate the power of AFM techniques in life sciences and nanomedicine.

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La robótica en el campo de la medicina ofrece un gran potencial y es motivo de investigación en numerosos centros en todo el mundo. Sin embargo, en sus distintos ámbitos: asistencia, rehabilitación y cirugía, encuentra todavía muchas limitaciones que condicionan su amplia implantación.

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Huntington disease (HD) is a neurodegenerative disorder that predominantly affects neurons of the forebrain. We have applied the Illumina massively parallel sequencing to deeply analyze the small RNA populations of two different forebrain areas, the frontal cortex (FC) and the striatum (ST) of healthy individuals and individuals with HD. More than 80% of the small-RNAs were annotated as microRNAs (miRNAs) in all samples. Deep sequencing revealed length and sequence heterogeneity (IsomiRs) for the vast majority of miRNAs. Around 80–90% of the miRNAs presented modifications in the 3′-terminus mainly in the form of trimming and/or as nucleotide addition variants, while the 5′-terminus of the miRNAs was specially protected from changes. Expression profiling showed strong miRNA and isomiR expression deregulation in HD, most being common to both FC and ST. The analysis of the upstream regulatory regions in co-regulated miRNAs suggests a role for RE1-Silencing Transcription Factor (REST) and P53 in miRNAs downregulation in HD. The putative targets of deregulated miRNAs and seed-region IsomiRs strongly suggest that their altered expression contributes to the aberrant gene expression in HD. Our results show that miRNA variability is a ubiquitous phenomenon in the adult human brain, which may influence gene expression in physiological and pathological conditions.

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In a previous study, we found that metaphase chromosomes are formed by thin plates, and here we have applied atomic force microscopy (AFM) and friction force measurements at the nanoscale (nanotribology) to analyze the properties of these planar structures in aqueous media at room temperature. Our results show that high concentrations of NaCl and EDTA and extensive digestion with protease and nuclease enzymes cause plate denaturation. Nanotribology studies show that native plates under structuring conditions (5 mM Mg2+) have a relatively high friction coefficient ( ≈ 0.3), which is markedly reduced when high concentrations of NaCl or EDTA are added ( ≈ 0.1). This lubricant effect can be interpreted considering the electrostatic repulsion between DNA phosphate groups and the AFM tip. Protease digestion increases the friction coefficient ( ≈ 0.5), but the highest friction is observed when DNA is cleaved by micrococcal nuclease ( ≈ 0.9), indicating that DNA is the main structural element of plates. Whereas nuclease-digested plates are irreversibly damaged after the friction measurement, native plates can absorb kinetic energy from the AFM tip without suffering any damage. These results suggest that plates are formed by a flexible and mechanically resistant two-dimensional network which allows the safe storage of DNA during mitosis.

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BACKGROUND:Ribonucleotide reduction is the only de novo pathway for synthesis of deoxyribonucleotides, the building blocks of DNA. The reaction is catalysed by ribonucleotide reductases (RNRs), an ancient enzyme family comprised of three classes. Each class has distinct operational constraints, and are broadly distributed across organisms from all three domains, though few class I RNRs have been identified in archaeal genomes, and classes II and III likewise appear rare across eukaryotes. In this study, we examine whether this distribution is best explained by presence of all three classes in the Last Universal Common Ancestor (LUCA), or by horizontal gene transfer (HGT) of RNR genes. We also examine to what extent environmental factors may have impacted the distribution of RNR classes.RESULTS:Our phylogenies show that the Last Eukaryotic Common Ancestor (LECA) possessed a class I RNR, but that the eukaryotic class I enzymes are not directly descended from class I RNRs in Archaea. Instead, our results indicate that archaeal class I RNR genes have been independently transferred from bacteria on two occasions. While LECA possessed a class I RNR, our trees indicate that this is ultimately bacterial in origin. We also find convincing evidence that eukaryotic class I RNR has been transferred to the Bacteroidetes, providing a stunning example of HGT from eukaryotes back to Bacteria. Based on our phylogenies and available genetic and genomic evidence, class II and III RNRs in eukaryotes also appear to have been transferred from Bacteria, with subsequent within-domain transfer between distantly-related eukaryotes. Under the three-domains hypothesis the RNR present in the last common ancestor of Archaea and eukaryotes appears, through a process of elimination, to have been a dimeric class II RNR, though limited sampling of eukaryotes precludes a firm conclusion as the data may be equally well accounted for by HGT.CONCLUSIONS:Horizontal gene transfer has clearly played an important role in the evolution of the RNR repertoire of organisms from all three domains of life. Our results clearly show that class I RNRs have spread to Archaea and eukaryotes via transfers from the bacterial domain, indicating that class I likely evolved in the Bacteria. However, against the backdrop of ongoing transfers, it is harder to establish whether class II or III RNRs were present in the LUCA, despite the fact that ribonucleotide reduction is an essential cellular reaction and was pivotal to the transition from RNA to DNA genomes. Instead, a general pattern of ongoing horizontal transmission emerges wherein environmental and enzyme operational constraints, especially the presence or absence of oxygen, are likely to be major determinants of the RNR repertoire of genomes.

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A partir de cambios legi s l at ivos y de cambios en las estrategias de financiación, la investigación en células madre en España ha experimentado una progresión espectacular, combinándose la investigación básica con la translacional. Los avances en este campo pueden suponer enormes beneficios en pos del desarrollo de la medicina regenerativa.

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Perspective projection presents objects as they are naturally seen by the eye. However, this type of mapping strongly distorts their geometric properties as angles, which are not preserved under perspective transformations. In this work, this angular variation serves to model the visual effect of perspective projection. Thus, knowing that the angular distortion depends on the point of view of the observer, it is demonstrated that it is possible to determine the pose of an object as a consequence of its perspective distortion. It is a computational approach to direct perception in which spatial information of a scene is calculated directly from the optic array. Experimental results show the robustness provided by the use of angles and establishes this 3D measurement technique as an emulation of a visual perception process.

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Understanding the relationships between material surface properties, behaviour of adsorbed proteins and cellular responses is essential to design optimal material surfaces for tissue engineering. In this study we modify thin layers of plasma polymerized hexamethyldisiloxane (PPHMDS) by ammonia treatment in order to increase surface wettability and the corresponding biological response. The physico-chemical properties of the polymer films were characterized by contact angle (CA) measurements and Fourier Transform Infrared Spectroscopy (FTIR) analysis.Human umbilical vein endothelial cells (HUVEC) were used as model system for the initial biocompatibility studies following their behavior upon preadsorption of polymer films with three adhesive proteins: fibronectin (FN), fibrinogen (FG) and vitronectin (VN). Adhesive interaction of HUVEC was evaluated after 2 hours by analyzing the overall cell morphology, and the organization of focal adhesion contacts and actin cytoskeleton. We have found similar good cellular response on FN and FG coated polymer films, with better pronounced vinculin expression on FN samples while. Conversely, on VN coated surfaces the wettability influenced significantly initial celular interaction spreading. The results obtained suggested that ammonia plasma treatment can modulate the biological activity of the adsorbed protein s on PPHMDS surfaces and thus to influence the interaction with endothelial cells.

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Human-Machine interfaces constitute a key factor to guarantee the effective use of technological equipment. In the field of image guided surgery and surgical robots, the availability of an adequate interaction means determines the suitability or not of a given technological aid. This work focuses on the problems surgeons find in planning and executing a robot assisted intervention. Analyzing the potential of computer graphics, together with the surgeons needs during, first, the planning and later on the development of a surgical intervention, the specifications and the implementation of an interface is described. In the design of this interface, special attention has been put on the gesture and attention capabilities that surgeons can devote to the interface

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The present study reports on how detonation nanodiamond (DND) - plasma poly(hexamethyldisiloxane) composites (PPHMDS) affect osteoblast cell behavior. It has been established that various modified DND nanoparticles (Ag-DND and Si-DND) can be readily integrated into virtually all polymer matrices. In particular, PPHDMS composites have been developed over the past few years because of the variety of their application as medical devices and implants. By incubation of MG-63 osteoblast-like cells on the surface of DND (Ag-DND and Si-DND) - PPHMDS composite, we tested the hypothesis that DND-based polymer composites can influence the adhesion behavior of MG-63 osteoblast-like cells. Morphological and structural characterization of DND, Ag-DND and Si-DND powders was carried out by XRD, HRTEM and EDS. For the study of the composite layers, deposited on cover glass (CG), FTIR spectroscopy has been performed in order to determine if the DND nanofiller can potentially modify the structural and chemical dynamics of the polymer matrix. The kinetic of static water contact angle of composite surfaces as a function of the as-used nanofiller DND's in polymer matrix was measured The results with MG-63 osteoblast-like cells suggest the potential of using DND-based polymer composites for application in engineering implantable scaffolds and devices.

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Bone problems affect millions of people across the world. In fact, musculoskeletal conditions such as joint pathologies, fractures related to osteoporosis, back pain, serious injuries and different sorts of bone diseases and disabilities are among the most common causes for hundreds of millions of people worldwide suffering acute and severe long-term pain and becoming physically handicapped. It has been reported that over 100 million Europeans are affected by different bone related problems and suffer chronic musculoskeletal pain, while in the US musculoskeletal problems affect over 40 million people aged 45 years and older. It is expected that the percentage of population affected by musculoskeletal conditions will double by the year 2020. Although morbidity is low, they have a major effect on disability, medical costs and patient quality of life [1,2]. Thus, bone defect treatments represent a significant medical and socioeconomic challenge

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Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions. While most definitions of tissue engineering cover a broad range of applications, in practice the term is closely associated with applications that repair or replace portions of or whole tissues (i.e., bone, cartilage, blood vessels, bladder, etc.). Often, the tissues involved require certain mechanical and structural properties for proper function. The term has also been applied to efforts to perform specific biochemical functions using cells within an artificially-created support system (e.g. an artificial pancreas, or a bioartificial liver). The term regenerative medicine is often used synonymously with tissue engineering, although those involved in regenerative medicine place more emphasis on the use of stem cells to produce tissues.

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The surface modification of biomaterials plays a significant role in determining the outcome of biological-material interactions. With the appropriate modification a material's surface can be tailored to improve biocompatibility, adhesion and cell interactions. Consequently surface modification is vital in the development and design of new biomaterials and medical devices. Surface modification of biomaterials reviews both established surface modifications and those still in the early stages of research and discusses how they can be used to optimise biological interactions and enhance clinical performance. Part one begins with chapters looking at various types and techniques of surface modification including plasma polymerisation, covalent binding of poly (ethylene glycol) (PEG), heparinisation, peptide functionalisation and calcium phosphate deposition before going on to examine metal surface oxidation and biomaterial surface topography to control cellular response with particular reference to technologies, cell behaviour and biomedical applications. Part two studies the analytical techniques and applications of surface modification with chapters on analysing biomaterial surface chemistry, surface structure, morphology and topography before moving onto discuss modifying biomaterial surfaces to optimise interactions with blood, control infection, optimise interactions with soft tissues, repair and regenerate nerve cells, control stem cell growth and differentiation and to optimise interactions with bone. The distinguished editor and international team of contributors to Surface modification of biomaterials have produced a unique overview and detailed chapters on a range of surface modification techniques which will provide an excellent resource for biomaterials researchers and scientists and engineers concerned with improving the properties of biomaterials. It will also be beneficial for academics researching surface modification.

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Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident cell within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches the cytoskeleton can stiffen, increase traction forces and reinforce, as reported by some, or can soften and fluidize, as reported more recently by our laboratory, but in any given circumstance it remains unknown which response might prevail or why. Using a novel nanotechnology, we show here that in loading conditions expected in most physiological circumstances the localized reinforcement response fails to scale up to the level of homogeneous cell stretch; fluidization trumps reinforcement. Whereas the reinforcement response is known to be mediated by upstream mechanosensing and downstream signaling, results presented here show the fluidization response to be altogether novel: it is a direct physical effect of mechanical force acting upon a structural lattice that is soft and fragile. Cytoskeletal softness and fragility, we argue, is consistent with early evolutionary adaptations of the eukaryotic cell to material properties of a soft inert microenvironment.

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A novel, versatile and robust technology to manufacture transparent micropipettes, suitable for biological applications, is presented here. Up to three deep reactive ion etchings have been included in the manufacturing process, providing highly controlled geometry of reservoirs, connection cavities and inlet ports. Etching processes have been used for the definition of chip and reservoir and for nozzle release. Additionally, special design considerations have been developed to facilitate micro-to-macro fluidic connections. Implementation of anodic bonding to seal a glass substrate to the fluidic structure etched on Si, allowed observation of the flow inside the reservoir. Flow tests have been conducted by filling channels with different fluids. Flow was observed under an optical microscope, both during capillary filling and also during pumping. Dispensing has been demonstrated by functionalizing the surface of an AFM cantilever. Mechanical tests performed by piercing live mouse cells with FIB-sharpened micropipettes suggest the design is sturdy for biological piercing applications.

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This paper presents the architecture of a novel implementation of an integrated self-powered system based on piezoelectric vibrations in a 0.13Îum technology. The electromechanical transduction is performed by using a low-cost commercial piezoelectric, working at low frequencies, with voltages up to 2.5V. The system is conceived as a System In a Package (SiP). The full integrated system is adapted to work with low-voltage and low-power conditions. The full custom power management circuit is used to charge a storage capacitor (super capacitor), from which the stored energy will be used to power, by controlled cycles of discharge operation of a very low power wireless sensor node that could be used in heavy machinery monitoring. Each circuitry block of the power management circuitry is presented and discussed. The simulated studies are fully validated by experimental tests. The experimental consumption of the power management unit is 67μW, approach to the theoretical expected value of 60ÎuW.

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In the present work, we have studied dynamic changes of QRS loop in the Vectocardiogram (VCG) of 80 patients that underwent Percutaneous Transluminal Coronary Angioplasty (PTCA). The VCG was obtained for each patient using the XYZ orthogonal leads of their electrocardiographic (ECG) records acquired before, during and after PTCA procedure. In order to analyze the variations of VCG, it has been proposed in this study the following parameters a) Maximum module of the cardiac depolarization vector, b) Volume, c) and Area of vectocardiographic loop corresponding to the QRS complex of each beat, d) Maximum distance between Centroid and the Loop, e) Angle between the XY plane and the Optimum Plane, f) Relation between the Area and Perimeter. The results obtained indicate that the parameters proposed show significant statistics differences (p-value<0.05) before, during (with some exceptions at the first minute of balloon inflation) and after PTCA. We conclude that the variations observed in the proposed parameters correctly represent not only the morphological changes in the depolarization VCG but also they reflect the modifications in the levels of cardiac ischemia induced by PTCA.

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In this work, it is proposed a technique for the feature extraction of electroencephalographic (EEG) signals for classification of mental tasks which is an important part in the development of Brain Computer Interfaces (BCI). The Empirical Mode Decomposition (EMD) is a method capable to process nonstationary and nonlinear signals as the EEG. This technique was applied in EEG signals of 7 subjects performing 5 mental tasks. For each mode obtained from the EMD and each EEG channel were computed six features: Root Mean Square (RMS), Variance, Shannon Entropy, Lempel-Ziv Complexity Value, and Central and Maximum Frequencies, obtaining a feature vector of 180 components. The Wilks' lambda parameter was applied for the selection of the most important variables reducing the dimensionality of the feature vector. The classification of mental tasks was performed using Linear Discriminate Analysis (LD) and Neural Networks (NN). With this method, the average classification over all subjects in database was 91±5% and 87±5% using LD and NN, respectively. It was concluded that the EMD allows getting better performances in the classification of mental tasks than the obtained with other traditional methods, like spectral analysis.

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The differentiation between obstructive and central respiratory events is one of the most recurrent tasks in the diagnosis of sleep disordered breathing. Esophageal pressure measurement is the gold-standard method to assess respiratory effort and identify these events. But as its invasiveness discourages its use in clinical routine, non-invasisve systems have been proposed for differentiation. However, their adoption has been slow due to their limited clinical validation, as the creation of manual, gold-standard validation sets by human experts is a cumbersome procedure. In this study, a new system is proposed for an objective automatic, gold-standard differentiation between obstructive and central hypopneas with the esophageal pressure signal. First, an overall of 356 hypopneas of 16 patients were manually scored by a human expert to create a gold-standard validation set. Then, features were extracted from each hypopnea to train and test classifiers (Discriminant Analysis, Support Vector Machines and adaboost classifiers) to differentiate between central and obstructive hypopneas with the gold-standard esophageal pressure signal. The automatic differentiation system achieved promising results, with a sensitivity of 0.88, a specificity of 0.93 and an accuracy of 0.90. Hence, this system seems promising for an automatic, gold-standard differentiation between obstructive and central hypopneas.

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An integrated front-end architecture for In-Vivo detection is presented. The system is conceived to be implanted under the human skin. The powering and communication between this device and an external primary transmitter are based on an inductive link. The presented architecture is oriented to two different approaches, defining a True/False alarm system, based on amperometric or impedance biosensors. The particular case of the amperometric sensor is used to validate the architecture in terms of different integrated modules fabricated in a 0.13μm technology. A potentiostat amplifier has been integrated to control an amperometric biosensor as well as a current sensing method based on a transimpedance amplifier is used to measure the current. It is also introduced the electronics designed for the bio-impedance case.

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A correntropy-based technique is proposed for the analysis and characterization of respiratory flow signals in chronic heart failure (CHF) patients with both periodic and nonperiodic breathing (PB and nPB), and healthy subjects. Correntropy is a novel similarity measure which provides information on temporal structure and statistical distribution simultaneously. Its properties lend itself to the definition of the correntropy spectral density (CSD). An interesting result from CSD-based spectral analysis is that both the respiratory frequency and modulation frequency can be detected at their original positions in the spectrum without prior demodulation of the flow signal. The respiratory pattern is characterized by a number of spectral parameters extracted from the respiratory and modulation frequency bands. The results show that the power of the modulation frequency band offers excellent performance when classifying CHF patients versus healthy subjects, with an accuracy of 95.3%, and nPB patients versus healthy subjects with 90.7%. The ratio between the power in the modulation and respiration frequency bands provides the best results classifying CHF patients into PB and nPB, with an accuracy of 88.9%.

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Epilepsy is a neurological disorder that affects around 50 million people worldwide. The seizure detection is an important component in the diagnosis of epilepsy. In this study, the Empirical Mode Decomposition (EMD) method was proposed on the development of an automatic epileptic seizure detection algorithm. The algorithm first computes the Intrinsic Mode Functions (IMFs) of EEG records, then calculates the energy of each IMF and performs the detection based on an energy threshold and a minimum duration decision. The algorithm was tested in 9 invasive EEG records provided and validated by the Epilepsy Center of the University Hospital of Freiburg. In 90 segments analyzed (39 with epileptic seizures) the sensitivity and specificity obtained with the method were of 56.41% and 75.86% respectively. It could be concluded that EMD is a promissory method for epileptic seizure detection in EEG records.

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The study of mechanomyographic (MMG) signals of respiratory muscles is a promising technique in order to evaluate the respiratory muscular effort. In this work MMG signals from left and right hemidiaphragm (MMGl and MMGr, respectively) acquired during a respiratory protocol have been analyzed. The acquisition of both MMG signals was carried out by means of two capacitive accelerometers placed on both left and right sides of the costal wall. The signals were recorded in a group of six patients with Chronic Obstructive Pulmonary Disease (COPD). It has been observed that with the increase of inspiratory pressure it takes place an increase of the amplitude and a displacement toward low frequencies in both left and right MMG signals. Furthermore, it has been seen that the increase of amplitude and the decrease of frequency in MMG signals are more pronounced in severe COPD patients. This behaviour is similar for both MMGl and MMGr signals. Results suggest that the use of MMG signals could be potentially useful for the evaluation of the respiratory muscular function in COPD patients.

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A biopotentiostat amplifier, for in-vivo applications, has been designed using a low-voltage lowpower technology of 0.13μm@1.2V. The purpose of the designed bio-amplifier is oriented to sense the capacitive variations of electrochemical biosensor experiments at low frequencies. The designed amplifier seeks to function with a very small power consumption and occupies a very small area, compared with other designs, looking for an in-vivo application. It occupies an area of 327μm × 260μm, and has an average power consumption of 51.2 μW. The performance of the bio-amplifier has been simulated and experimentally validated.

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The Lempel-Ziv complexity (LZ) has been widely used to evaluate the randomness of finite sequences. In general, the LZ complexity has been used to determine the complexity grade present in biomedical signals. The LZ complexity is not able to discern between signals with different amplitude variations and similar random components. On the other hand, amplitude parameters, as the root mean square (RMS), are not able to discern between signals with similar power distributions and different random components. In this work, we present a novel method to quantify amplitude and complexity variations in biomedical signals by means of the computation of the LZ coefficient using more than two quantification states, and with thresholds fixed and independent of the dynamic range or standard deviation of the analyzed signal: the Multistate Lempel-Ziv (MLZ) index. Our results indicate that MLZ index with few quantification levels only evaluate the complexity changes of the signal, with high number of levels, the amplitude variations, and with an intermediate number of levels informs about both amplitude and complexity variations. The study performed in diaphragmatic mechanomyographic signals shows that the amplitude variations of this signal are more correlated with the respiratory effort than the complexity variations. Furthermore, it has been observed that the MLZ index with high number of levels practically is not affected by the existence of impulsive, sinusoidal, constant and Gaussian noises compared with the RMS amplitude parameter.

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An apnea detection method based on spectral analysis was used to assess the performance of three ECG derived respiratory (EDR) signals. They were obtained on R wave area (EDR1), heart rate variability (EDR2) and R peak amplitude (EDR3) of ECG record in 8 patients with sleep apnea syndrome. The mean, central, peak and first quartile frequencies were computed from the spectrum every 1 min for each EDR. For each frequency parameter a threshold-based decision was carried out on every 1 min segment of the three EDR, classifying it as 'apnea' when its frequency value was below a determined threshold or as 'not apnea' in other cases. Results indicated that EDR1, based on R wave area has better performance in detecting apnea episodes with values of specificity (Sp) and sensitivity (Se) near 90%; EDR2 showed similar Sp but lower Se (78%); whereas EDR3 based on R peak amplitude did not detect appropriately the apneas episodes reaching Sp and Se values near 60%.

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In this work we studied dynamic changes of ventricular depolarization loop evolution based on the Singular Value Decomposition (SVD) technique of 80 patients that underwent Percutaneous Transluminal Coronary Angioplasty (PTCA). The 8 independent ECG leads are subjected to SVD technique and are used to construct a new representation of QRS-SVD loops. In order to analyze the variations of QRS-SVD loops before, during and after PTCA, we proposed the following parameters: Maximum Module of the Depolarization Vector, Planar Area, Maximum Distance between Centroid and the Loop, Angle between the S1S2 plane and the Optimum Plane and Ratio between the Area and Perimeter. The results indicated that the parameters proposed show significant statistics differences during and after PTCA procedure vs. control. We concluded that the variations in the QRS-SVD loop before, during and after PTCA at ventricular depolarization can be described correctly through the proposed parameters.

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Patients with chronic heart failure (CHF) with periodic breathing (PB) and Cheyne-Stokes respiration (CSR) tend to exhibit higher mortality and poor prognosis. This study proposes the characterization of respiratory patterns in CHF patients and healthy subjects using the envelope of the respiratory flow signal, and autoregressive (AR) time-frequency analysis. In time-varying respiratory patterns, the statistical distribution of the AR coefficients, pole locations, and the spectral parameters that characterize the discriminant band are evaluated to identify typical breathing patterns. In order to evaluate the accuracy of this characterization, a feature selection process followed by linear discriminant analysis is applied. 26 CHF patients (8 patients with PB pattern and 18 with non-periodic breathing pattern (nPB)) are studied. The results show an accuracy of 83.9% with the mean of the main pole magnitude and the mean of the total power, when classifying CHF patients versus healthy subjects, and 83.3% for nPB versus healthy subjects. The best result when classifying CHF patients into PB and nPB was an accuracy of 88.9%, using the coefficient of variation of the first AR coefficient and the mean of the total power.

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Evanescent field optical biosensors are label free sensors that measure the variation of the refractive index of the adsorbed layer onto a chip surface and translate this variation into surface concentration of the adsorbed molecule. The evanescent field based techniques depend on a theoretical model of the waveguide to determine the desired parameters of the adsorbed layer. As this layer is not only composed by the biomolecules, but also by some amount of the buffer solution, in this study, we have developed a new calibration method to take into account the refractive index buffer changes. We report a new methodology to characterize each sensor chip before the measurements and we present the refractive indexes of different buffer solutions considering the most common ones used in biosensor applications. This work will set the calibration bases for any optical grating biosensor instrument.

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- provides a comprehensive review of the materials science, engineering principles and recent advances in this important area - reviews the fundamentals of bone repair and regeneration addressing social, economic and clinical challenges - examines the properties of biomaterials used for bone repair with specific chapters assessing metals, ceramics, polymers and composites - discusses clinical applications and considerations including orthopaedic surgery and bone tissue engineering Bone repair is a fundamental part of the rapidly expanding medical care sector and has benefited from many recent technological developments. With an increasing number of technologies available, it is vital that the correct technique is selected for specific clinical procedures. This unique book will provide a comprehensive review of the materials science, engineering principles and recent advances in this important area. The first part of the book reviews the fundamentals of bone repair and regeneration. Chapters in the second part discuss the science and properties of biomaterials used for bone repair such as metals, ceramics, polymers and composites. The final section of the book discusses clinical applications and considerations with chapters on such topics as orthopaedic surgery, tissue engineering, implant retrieval and ethics of bone repair biomaterials. With its distinguished editors and team of international contributors, Bone repair biomaterials is an invaluable reference for researchers and clinicians within the biomedical industry and academia.

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Biological processes often involve multimolecular interactions on a nanometre scale or at very large molecular concentrations, making them difficult to visualize. Optical antennas have the potential to become powerful tools for nanobioimaging by enhancing optical fields on this tiny scale.

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Chemical modification with photoisomerizable tethered ligands endows proteins with sensitivity to light. These optically actuated proteins are revolutionizing research in biology by making it possible to manipulate biological processes noninvasively and with unprecedented spatiotemporal resolution.

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Luminescence blinking of single emitters is one of the most profound and intriguing issues in nano-optics and related areas. Its mechanisms and in particular the often observed deviant power-law statistics are a subject of ongoing recent debate. We examine onoff blinking in a dedicated synthetic trichromophoric assembly of perylene molecules. This trimeric system allows us to unambiguously discern blinking from photobleaching events and furthermore displays sufficient blinking events for a single-molecule analysis. An intriguing memory effect is observed, evidenced in clear correlations between successive on-times. In contrast, successive off-times are only weakly correlated and cross-correlations between on- and off-times are absent. Our results reveal the importance of nanoscale environmental dynamics on top of charge tunneling in understanding single emitter luminescence blinking. Dynamics of the polymer matrix and charge carriers therein is crucial to explain the power-law distribution of on-times. This result is directly relevant for related systems like semiconductor quantum dots, fluorescent proteins, and conjugated polymers.

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