979 resultados para Time-resolved methods


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Catering to society's demand for high performance computing, billions of transistors are now integrated on IC chips to deliver unprecedented performances. With increasing transistor density, the power consumption/density is growing exponentially. The increasing power consumption directly translates to the high chip temperature, which not only raises the packaging/cooling costs, but also degrades the performance/reliability and life span of the computing systems. Moreover, high chip temperature also greatly increases the leakage power consumption, which is becoming more and more significant with the continuous scaling of the transistor size. As the semiconductor industry continues to evolve, power and thermal challenges have become the most critical challenges in the design of new generations of computing systems. ^ In this dissertation, we addressed the power/thermal issues from the system-level perspective. Specifically, we sought to employ real-time scheduling methods to optimize the power/thermal efficiency of the real-time computing systems, with leakage/ temperature dependency taken into consideration. In our research, we first explored the fundamental principles on how to employ dynamic voltage scaling (DVS) techniques to reduce the peak operating temperature when running a real-time application on a single core platform. We further proposed a novel real-time scheduling method, “M-Oscillations” to reduce the peak temperature when scheduling a hard real-time periodic task set. We also developed three checking methods to guarantee the feasibility of a periodic real-time schedule under peak temperature constraint. We further extended our research from single core platform to multi-core platform. We investigated the energy estimation problem on the multi-core platforms and developed a light weight and accurate method to calculate the energy consumption for a given voltage schedule on a multi-core platform. Finally, we concluded the dissertation with elaborated discussions of future extensions of our research. ^

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Providing transportation system operators and travelers with accurate travel time information allows them to make more informed decisions, yielding benefits for individual travelers and for the entire transportation system. Most existing advanced traveler information systems (ATIS) and advanced traffic management systems (ATMS) use instantaneous travel time values estimated based on the current measurements, assuming that traffic conditions remain constant in the near future. For more effective applications, it has been proposed that ATIS and ATMS should use travel times predicted for short-term future conditions rather than instantaneous travel times measured or estimated for current conditions. This dissertation research investigates short-term freeway travel time prediction using Dynamic Neural Networks (DNN) based on traffic detector data collected by radar traffic detectors installed along a freeway corridor. DNN comprises a class of neural networks that are particularly suitable for predicting variables like travel time, but has not been adequately investigated for this purpose. Before this investigation, it was necessary to identifying methods for data imputation to account for missing data usually encountered when collecting data using traffic detectors. It was also necessary to identify a method to estimate the travel time on the freeway corridor based on data collected using point traffic detectors. A new travel time estimation method referred to as the Piecewise Constant Acceleration Based (PCAB) method was developed and compared with other methods reported in the literatures. The results show that one of the simple travel time estimation methods (the average speed method) can work as well as the PCAB method, and both of them out-perform other methods. This study also compared the travel time prediction performance of three different DNN topologies with different memory setups. The results show that one DNN topology (the time-delay neural networks) out-performs the other two DNN topologies for the investigated prediction problem. This topology also performs slightly better than the simple multilayer perceptron (MLP) neural network topology that has been used in a number of previous studies for travel time prediction.

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Context: The stellar population of the 30 Doradus star-forming region in the Large Magellanic Cloud contains a subset of apparently single, rapidly rotating O-type stars. The physical processes leading to the formation of this cohort are currently uncertain. 

Aims: One member of this group, the late O-type star VFTS 399, is found to be unexpectedly X-ray bright for its bolometric luminosity-in this study we aim to determine its physical nature and the cause of this behaviour. 

Methods: To accomplish this we performed a time-resolved analysis of optical, infrared and X-ray observations. 

Results: We found VFTS 399 to be an aperiodic photometric variable with an apparent near-IR excess. Its optical spectrum demonstrates complex emission profiles in the lower Balmer series and select He i lines-taken together these suggest an OeBe classification. The highly variable X-ray luminosity is too great to be produced by a single star, while the hard, non-thermal nature suggests the presence of an accreting relativistic companion. Finally, the detection of periodic modulation of the X-ray lightcurve is most naturally explained under the assumption that the accretor is a neutron star. 

Conclusions: VFTS 399 appears to be the first high-mass X-ray binary identified within 30 Dor, sharing many observational characteristics with classical Be X-ray binaries. Comparison of the current properties of VFTS 399 to binary-evolution models suggests a progenitor mass 25 M for the putative neutron star, which may host a magnetic field comparable in strength to those of magnetars. VFTS 399 is now the second member of the cohort of rapidly rotating "single" O-type stars in 30 Dor to show evidence of binary interaction resulting in spin-up, suggesting that this may be a viable evolutionary pathway for the formation of a subset of this stellar population.

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Membrane proteins, which reside in the membranes of cells, play a critical role in many important biological processes including cellular signaling, immune response, and material and energy transduction. Because of their key role in maintaining the environment within cells and facilitating intercellular interactions, understanding the function of these proteins is of tremendous medical and biochemical significance. Indeed, the malfunction of membrane proteins has been linked to numerous diseases including diabetes, cirrhosis of the liver, cystic fibrosis, cancer, Alzheimer's disease, hypertension, epilepsy, cataracts, tubulopathy, leukodystrophy, Leigh syndrome, anemia, sensorineural deafness, and hypertrophic cardiomyopathy.1-3 However, the structure of many of these proteins and the changes in their structure that lead to disease-related malfunctions are not well understood. Additionally, at least 60% of the pharmaceuticals currently available are thought to target membrane proteins, despite the fact that their exact mode of operation is not known.4-6 Developing a detailed understanding of the function of a protein is achieved by coupling biochemical experiments with knowledge of the structure of the protein. Currently the most common method for obtaining three-dimensional structure information is X-ray crystallography. However, no a priori methods are currently available to predict crystallization conditions for a given protein.7-14 This limitation is currently overcome by screening a large number of possible combinations of precipitants, buffer, salt, and pH conditions to identify conditions that are conducive to crystal nucleation and growth.7,9,11,15-24 Unfortunately, these screening efforts are often limited by difficulties associated with quantity and purity of available protein samples. While the two most significant bottlenecks for protein structure determination in general are the (i) obtaining sufficient quantities of high quality protein samples and (ii) growing high quality protein crystals that are suitable for X-ray structure determination,7,20,21,23,25-47 membrane proteins present additional challenges. For crystallization it is necessary to extract the membrane proteins from the cellular membrane. However, this process often leads to denaturation. In fact, membrane proteins have proven to be so difficult to crystallize that of the more than 66,000 structures deposited in the Protein Data Bank,48 less than 1% are for membrane proteins, with even fewer present at high resolution (< 2Å)4,6,49 and only a handful are human membrane proteins.49 A variety of strategies including detergent solubilization50-53 and the use of artificial membrane-like environments have been developed to circumvent this challenge.43,53-55 In recent years, the use of a lipidic mesophase as a medium for crystallizing membrane proteins has been demonstrated to increase success for a wide range of membrane proteins, including human receptor proteins.54,56-62 This in meso method for membrane protein crystallization, however, is still by no means routine due to challenges related to sample preparation at sub-microliter volumes and to crystal harvesting and X-ray data collection. This dissertation presents various aspects of the development of a microfluidic platform to enable high throughput in meso membrane protein crystallization at a level beyond the capabilities of current technologies. Microfluidic platforms for protein crystallization and other lab-on-a-chip applications have been well demonstrated.9,63-66 These integrated chips provide fine control over transport phenomena and the ability to perform high throughput analyses via highly integrated fluid networks. However, the development of microfluidic platforms for in meso protein crystallization required the development of strategies to cope with extremely viscous and non-Newtonian fluids. A theoretical treatment of highly viscous fluids in microfluidic devices is presented in Chapter 3, followed by the application of these strategies for the development of a microfluidic mixer capable of preparing a mesophase sample for in meso crystallization at a scale of less than 20 nL in Chapter 4. This approach was validated with the successful on chip in meso crystallization of the membrane protein bacteriorhodopsin. In summary, this is the first report of a microfluidic platform capable of performing in meso crystallization on-chip, representing a 1000x reduction in the scale at which mesophase trials can be prepared. Once protein crystals have formed, they are typically harvested from the droplet they were grown in and mounted for crystallographic analysis. Despite the high throughput automation present in nearly all other aspects of protein structure determination, the harvesting and mounting of crystals is still largely a manual process. Furthermore, during mounting the fragile protein crystals can potentially be damaged, both from physical and environmental shock. To circumvent these challenges an X-ray transparent microfluidic device architecture was developed to couple the benefits of scale, integration, and precise fluid control with the ability to perform in situ X-ray analysis (Chapter 5). This approach was validated successfully by crystallization and subsequent on-chip analysis of the soluble proteins lysozyme, thaumatin, and ribonuclease A and will be extended to microfluidic platforms for in meso membrane protein crystallization. The ability to perform in situ X-ray analysis was shown to provide extremely high quality diffraction data, in part as a result of not being affected by damage due to physical handling of the crystals. As part of the work described in this thesis, a variety of data collection strategies for in situ data analysis were also tested, including merging of small slices of data from a large number of crystals grown on a single chip, to allow for diffraction analysis at biologically relevant temperatures. While such strategies have been applied previously,57,59,61,67 they are potentially challenging when applied via traditional methods due to the need to grow and then mount a large number of crystals with minimal crystal-to-crystal variability. The integrated nature of microfluidic platforms easily enables the generation of a large number of reproducible crystallization trials. This, coupled with in situ analysis capabilities has the potential of being able to acquire high resolution structural data of proteins at biologically relevant conditions for which only small crystals, or crystals which are adversely affected by standard cryocooling techniques, could be obtained (Chapters 5 and 6). While the main focus of protein crystallography is to obtain three-dimensional protein structures, the results of typical experiments provide only a static picture of the protein. The use of polychromatic or Laue X-ray diffraction methods enables the collection of time resolved structural information. These experiments are very sensitive to crystal quality, however, and often suffer from severe radiation damage due to the intense polychromatic X-ray beams. Here, as before, the ability to perform in situ X-ray analysis on many small protein crystals within a microfluidic crystallization platform has the potential to overcome these challenges. An automated method for collecting a "single-shot" of data from a large number of crystals was developed in collaboration with the BioCARS team at the Advanced Photon Source at Argonne National Laboratory (Chapter 6). The work described in this thesis shows that, even more so than for traditional structure determination efforts, the ability to grow and analyze a large number of high quality crystals is critical to enable time resolved structural studies of novel proteins. In addition to enabling X-ray crystallography experiments, the development of X-ray transparent microfluidic platforms also has tremendous potential to answer other scientific questions, such as unraveling the mechanism of in meso crystallization. For instance, the lipidic mesophases utilized during in meso membrane protein crystallization can be characterized by small angle X-ray diffraction analysis. Coupling in situ analysis with microfluidic platforms capable of preparing these difficult mesophase samples at very small volumes has tremendous potential to enable the high throughput analysis of these systems on a scale that is not reasonably achievable using conventional sample preparation strategies (Chapter 7). In collaboration with the LS-CAT team at the Advanced Photon Source, an experimental station for small angle X-ray analysis coupled with the high quality visualization capabilities needed to target specific microfluidic samples on a highly integrated chip is under development. Characterizing the phase behavior of these mesophase systems and the effects of various additives present in crystallization trials is key for developing an understanding of how in meso crystallization occurs. A long term goal of these studies is to enable the rational design of in meso crystallization experiments so as to avoid or limit the need for high throughput screening efforts. In summary, this thesis describes the development of microfluidic platforms for protein crystallization with in situ analysis capabilities. Coupling the ability to perform in situ analysis with the small scale, fine control, and the high throughput nature of microfluidic platforms has tremendous potential to enable a new generation of crystallographic studies and facilitate the structure determination of important biological targets. The development of platforms for in meso membrane protein crystallization is particularly significant because they enable the preparation of highly viscous mixtures at a previously unachievable scale. Work in these areas is ongoing and has tremendous potential to improve not only current the methods of protein crystallization and crystallography, but also to enhance our knowledge of the structure and function of proteins which could have a significant scientific and medical impact on society as a whole. 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The recently discovered abilities to synthesize single-walled carbon nanotubes and prepare single layer graphene have spurred interest in these sp2-bonded carbon nanostructures. In particular, studies of their potential use in electronic devices are many as silicon integrated circuits are encountering processing limitations, quantum effects, and thermal management issues due to rapid device scaling. Nanotube and graphene implementation in devices does come with significant hurdles itself. Among these issues are the ability to dope these materials and understanding what influences defects have on expected properties. Because these nanostructures are entirely all-surface, with every atom exposed to ambient, introduction of defects and doping by chemical means is expected to be an effective route for addressing these issues. Raman spectroscopy has been a proven characterization method for understanding vibrational and even electronic structure of graphene, nanotubes, and graphite, especially when combined with electrical measurements, due to a wealth of information contained in each spectrum. In Chapter 1, a discussion of the electronic structure of graphene is presented. This outlines the foundation for all sp2-bonded carbon electronic properties and is easily extended to carbon nanotubes. Motivation for why these materials are of interest is readily gained. Chapter 2 presents various synthesis/preparation methods for both nanotubes and graphene, discusses fabrication techniques for making devices, and describes characterization methods such as electrical measurements as well as static and time-resolved Raman spectroscopy. Chapter 3 outlines changes in the Raman spectra of individual metallic single-walled carbon nantoubes (SWNTs) upon sidewall covalent bond formation. It is observed that the initial degree of disorder has a strong influence on covalent sidewall functionalization which has implications on developing electronically selective covalent chemistries and assessing their selectivity in separating metallic and semiconducting SWNTs. Chapter 4 describes how optical phonon population extinction lifetime is affected by covalent functionalization and doping and includes discussions on static Raman linewidths. Increasing defect concentration is shown to decrease G-band phonon population lifetime and increase G-band linewidth. Doping only increases G-band linewidth, leaving non-equilibrium population decay rate unaffected. Phonon mediated electron scattering is especially strong in nanotubes making optical phonon decay of interest for device applications. Optical phonon decay also has implications on device thermal management. Chapter 5 treats doping of graphene showing ambient air can lead to inadvertent Fermi level shifts which exemplifies the sensitivity that sp2-bonded carbon nanostructures have to chemical doping through sidewall adsorption. Removal of this doping allows for an investigation of electron-phonon coupling dependence on temperature, also of interest for devices operating above room temperature. Finally, in Chapter 6, utilizing the information obtained in previous chapters, single carbon nanotube diodes are fabricated and characterized. Electrical performance shows these diodes are nearly ideal and photovoltaic response yields 1.4 nA and 205 mV of short circuit current and open circuit voltage from a single nanotube device. A summary and discussion of future directions in Chapter 7 concludes my work.

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Biofilms are the primary cause of clinical bacterial infections and are impervious to typical amounts of antibiotics, necessitating very high doses for treatment. Therefore, it is highly desirable to develop new alternate methods of treatment that can complement or replace existing approaches using significantly lower doses of antibiotics. Current standards for studying biofilms are based on end-point studies that are invasive and destroy the biofilm during characterization. This dissertation presents the development of a novel real-time sensing and treatment technology to aid in the non-invasive characterization, monitoring and treatment of bacterial biofilms. The technology is demonstrated through the use of a high-throughput bifurcation based microfluidic reactor that enables simulation of flow conditions similar to indwelling medical devices. The integrated microsystem developed in this work incorporates the advantages of previous in vitro platforms while attempting to overcome some of their limitations. Biofilm formation is extremely sensitive to various growth parameters that cause large variability in biofilms between repeated experiments. In this work we investigate the use of microfluidic bifurcations for the reduction in biofilm growth variance. The microfluidic flow cell designed here spatially sections a single biofilm into multiple channels using microfluidic flow bifurcation. Biofilms grown in the bifurcated device were evaluated and verified for reduced biofilm growth variance using standard techniques like confocal microscopy. This uniformity in biofilm growth allows for reliable comparison and evaluation of new treatments with integrated controls on a single device. Biofilm partitioning was demonstrated using the bifurcation device by exposing three of the four channels to various treatments. We studied a novel bacterial biofilm treatment independent of traditional antibiotics using only small molecule inhibitors of bacterial quorum sensing (analogs) in combination with low electric fields. Studies using the bifurcation-based microfluidic flow cell integrated with real-time transduction methods and macro-scale end-point testing of the combination treatment showed a significant decrease in biomass compared to the untreated controls and well-known treatments such as antibiotics. To understand the possible mechanism of action of electric field-based treatments, fundamental treatment efficacy studies focusing on the effect of the energy of the applied electrical signal were performed. It was shown that the total energy and not the type of the applied electrical signal affects the effectiveness of the treatment. The linear dependence of the treatment efficacy on the applied electrical energy was also demonstrated. The integrated bifurcation-based microfluidic platform is the first microsystem that enables biofilm growth with reduced variance, as well as continuous real-time threshold-activated feedback monitoring and treatment using low electric fields. The sensors detect biofilm growth by monitoring the change in impedance across the interdigitated electrodes. Using the measured impedance change and user inputs provided through a convenient and simple graphical interface, a custom-built MATLAB control module intelligently switches the system into and out of treatment mode. Using this self-governing microsystem, in situ biofilm treatment based on the principles of the bioelectric effect was demonstrated by exposing two of the channels of the integrated bifurcation device to low doses of antibiotics.

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Catering to society’s demand for high performance computing, billions of transistors are now integrated on IC chips to deliver unprecedented performances. With increasing transistor density, the power consumption/density is growing exponentially. The increasing power consumption directly translates to the high chip temperature, which not only raises the packaging/cooling costs, but also degrades the performance/reliability and life span of the computing systems. Moreover, high chip temperature also greatly increases the leakage power consumption, which is becoming more and more significant with the continuous scaling of the transistor size. As the semiconductor industry continues to evolve, power and thermal challenges have become the most critical challenges in the design of new generations of computing systems. In this dissertation, we addressed the power/thermal issues from the system-level perspective. Specifically, we sought to employ real-time scheduling methods to optimize the power/thermal efficiency of the real-time computing systems, with leakage/ temperature dependency taken into consideration. In our research, we first explored the fundamental principles on how to employ dynamic voltage scaling (DVS) techniques to reduce the peak operating temperature when running a real-time application on a single core platform. We further proposed a novel real-time scheduling method, “M-Oscillations” to reduce the peak temperature when scheduling a hard real-time periodic task set. We also developed three checking methods to guarantee the feasibility of a periodic real-time schedule under peak temperature constraint. We further extended our research from single core platform to multi-core platform. We investigated the energy estimation problem on the multi-core platforms and developed a light weight and accurate method to calculate the energy consumption for a given voltage schedule on a multi-core platform. Finally, we concluded the dissertation with elaborated discussions of future extensions of our research.

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BACKGROUND: Errors in the decision-making process are probably the main threat to patient safety in the prehospital setting. The reason can be the change of focus in prehospital care from the traditional "scoop and run" practice to a more complex assessment and this new focus imposes real demands on clinical judgment. The use of Clinical Guidelines (CG) is a common strategy for cognitively supporting the prehospital providers. However, there are studies that suggest that the compliance with CG in some cases is low in the prehospital setting. One possible way to increase compliance with guidelines could be to introduce guidelines in a Computerized Decision Support System (CDSS). There is limited evidence relating to the effect of CDSS in a prehospital setting. The present study aimed to evaluate the effect of CDSS on compliance with the basic assessment process described in the prehospital CG and the effect of On Scene Time (OST). METHODS: In this time-series study, data from prehospital medical records were collected on a weekly basis during the study period. Medical records were rated with the guidance of a rating protocol and data on OST were collected. The difference between baseline and the intervention period was assessed by a segmented regression. RESULTS: In this study, 371 patients were included. Compliance with the assessment process described in the prehospital CG was stable during the baseline period. Following the introduction of the CDSS, compliance rose significantly. The post-intervention slope was stable. The CDSS had no significant effect on OST. CONCLUSIONS: The use of CDSS in prehospital care has the ability to increase compliance with the assessment process of patients with a medical emergency. This study was unable to demonstrate any effects of OST.

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Nitrobenzoxadiazole (NBD)-labeled lipids are popular fluorescent membrane probes. However, the understanding of important aspects of the photophysics of NBD remains incomplete, including the observed shift in the emission spectrum of NBD-lipids to longer wavelengths following excitation at the red edge of the absorption spectrum (red-edge excitation shift or REES). REES of NBD-lipids in membrane environments has been previously interpreted as reflecting restricted mobility of solvent surrounding the fluorophore. However, this requires a large change in the dipole moment (Dm) of NBD upon excitation. Previous calculations of the value of Dm of NBD in the literature have been carried out using outdated semi-empirical methods, leading to conflicting values. Using up-to-date density functional theory methods, we recalculated the value of Dm and verified that it is rather small (B2 D). Fluorescence measurements confirmed that the value of REES is B16 nm for 1,2-dioleoyl-sn-glycero-3- phospho-L-serine-N-(NBD) (NBD-PS) in dioleoylphosphatidylcholine vesicles. However, the observed shift is independent of both the temperature and the presence of cholesterol and is therefore insensitive to the mobility and hydration of the membrane. Moreover, red-edge excitation leads to an increased contribution of the decay component with a shorter lifetime, whereas time-resolved emission spectra of NBD-PS displayed an atypical blue shift following excitation. This excludes restrictions to solvent relaxation as the cause of the measured REES and TRES of NBD, pointing instead to the heterogeneous transverse location of probes as the origin of these effects. The latter hypothesis was confirmed by molecular dynamics simulations, from which the calculated heterogeneity of the hydration and location of NBD correlated with the measured fluorescence lifetimes/REES. Globally, our combination of theoretical and experiment-based techniques has led to a considerably improved understanding of the photophysics of NBD and a reinterpretation of its REES in particular.

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Social interactions have been the focus of social science research for a century, but their study has recently been revolutionized by novel data sources and by methods from computer science, network science, and complex systems science. The study of social interactions is crucial for understanding complex societal behaviours. Social interactions are naturally represented as networks, which have emerged as a unifying mathematical language to understand structural and dynamical aspects of socio-technical systems. Networks are, however, highly dimensional objects, especially when considering the scales of real-world systems and the need to model the temporal dimension. Hence the study of empirical data from social systems is challenging both from a conceptual and a computational standpoint. A possible approach to tackling such a challenge is to use dimensionality reduction techniques that represent network entities in a low-dimensional feature space, preserving some desired properties of the original data. Low-dimensional vector space representations, also known as network embeddings, have been extensively studied, also as a way to feed network data to machine learning algorithms. Network embeddings were initially developed for static networks and then extended to incorporate temporal network data. We focus on dimensionality reduction techniques for time-resolved social interaction data modelled as temporal networks. We introduce a novel embedding technique that models the temporal and structural similarities of events rather than nodes. Using empirical data on social interactions, we show that this representation captures information relevant for the study of dynamical processes unfolding over the network, such as epidemic spreading. We then turn to another large-scale dataset on social interactions: a popular Web-based crowdfunding platform. We show that tensor-based representations of the data and dimensionality reduction techniques such as tensor factorization allow us to uncover the structural and temporal aspects of the system and to relate them to geographic and temporal activity patterns.

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Questa tesi mira a presentare una panoramica, anche sperimentale con dati editi ed inediti, della ricostruzione delle life histories umane mediante metodi istologici e biogeochimici applicati allo smalto dentale delle dentizioni decidue. La tesi si concentra sulle metodologie biogeochimiche ad alta risoluzione spaziale che consentono di ottenere livelli temporali di dettaglio senza precedenti (da stagionali fino a sub-settimanali), quando combinate con l'analisi istomorfometrica dei tessuti dentali mineralizzati. La presente ricerca si concentra sulla creazione di modelli consistenti di variazione delle concentrazioni di elementi in traccia (con particolare riferimento a stronzio e bario) lungo la giunzione smalto dentinale, ottenuti tramite LA-ICPMS (Laser Ablation Inductively Coupled Mass Spectrometry), in funzione dei cambiamenti nella dieta (allattamento, svezzamento) nel primo anno di età di individui a storia nutrizionale nota (utilizzando denti decidui naturalmente esfoliati). In una prospettiva bioarcheologica, i risultati delle indagini sulla dieta altamente risolte nel tempo e interpretate con modelli come quelli proposti si correlano direttamente alle life histories individuali e consentono una analisi più sfumata e completa del comportamento umano nel passato, fornendo informazioni essenziali per la comprensione degli adattamenti bioculturali e aprendo finestre conoscitive su aspetti quali il rapporto madre-progenie, la gravidanza, l’allattamento, lo stress infantile, la dieta sia della progenie che della madre, la mobilità ad alta risoluzione e molti altri aspetti della vita delle popolazioni del passato che lo studio del DNA antico e della morfologia scheletrica non possono fornire. Dove il DNA antico tace, lo studio avanzato delle life histories parla.

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Health economic evaluations require estimates of expected survival from patients receiving different interventions, often over a lifetime. However, data on the patients of interest are typically only available for a much shorter follow-up time, from randomised trials or cohorts. Previous work showed how to use general population mortality to improve extrapolations of the short-term data, assuming a constant additive or multiplicative effect on the hazards for all-cause mortality for study patients relative to the general population. A more plausible assumption may be a constant effect on the hazard for the specific cause of death targeted by the treatments. To address this problem, we use independent parametric survival models for cause-specific mortality among the general population. Because causes of death are unobserved for the patients of interest, a polyhazard model is used to express their all-cause mortality as a sum of latent cause-specific hazards. Assuming proportional cause-specific hazards between the general and study populations then allows us to extrapolate mortality of the patients of interest to the long term. A Bayesian framework is used to jointly model all sources of data. By simulation, we show that ignoring cause-specific hazards leads to biased estimates of mean survival when the proportion of deaths due to the cause of interest changes through time. The methods are applied to an evaluation of implantable cardioverter defibrillators for the prevention of sudden cardiac death among patients with cardiac arrhythmia. After accounting for cause-specific mortality, substantial differences are seen in estimates of life years gained from implantable cardioverter defibrillators.

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The aim of this work was to evaluate the performance of femtosecond laser-induced breakdown spectroscopy (fs-LIBS) for the determination of elements in animal tissues. Sample pellets were prepared from certified reference materials, such as liver, kidney, muscle, hepatopancreas, and oyster, after cryogenic grinding assisted homogenization. Individual samples were placed in a two-axis computer-controlled translation stage that moved in the plane orthogonal to a beam originating from a Ti:Sapphire chirped-pulse amplification (CPA) laser system operating at 800 mu and producing a train of 840 mu J and 40 fs pulses at 90 Hz. The plasma emission was coupled into the optical fiber of a high-resolution intensified charge-coupled device (ICCD)-echelle spectrometer. Time-resolved characteristics of the laser-produced plasmas showed that the best results were obtained with delay times between 80 and 120 ns. Data obtained indicate both that it is a matrix-independent sampling process and that fs-LIBS can be used for the determination of Ca, Cu, Fe, K, Mg, Na, and P, but efforts must be made to obtain more appropriate detection limits for Al, Sr, and Zn.