The analysis and detection of new psychoactive substances in biological matrices

New psychoactive substances (NPSs) have appeared on the recreational drug market at an unprecedented rate in recent years. Many are not new drugs but failed products of the pharmaceutical industry. The speed and variety of drugs entering the market poses a new complex challenge for the forensic toxicology community. The detection of these substances in biological matrices can be difficult as the exact compounds of interest may not be known. Many NPS are sold under the same brand name and therefore users themselves may not know what substances they have ingested. The majority of analytical methods for the detection of NPSs tend to focus on a specific class of compounds rather than a wide variety. In response to this, a robust and sensitive method was developed for the analysis of various NPS by solid phase extraction (SPE) with gas chromatography mass spectrometry (GCMS). Sample preparation and derivatisation were optimised testing a range of SPE cartridges and derivatising agents, as well as derivatisation incubation time and temperature. The final gas chromatography mass spectrometry method was validated in accordance with SWGTOX 2013 guidelines over a wide concentration range for both blood and urine for 23 and 25 analytes respectively. This included the validation of 8 NBOMe compounds in blood and 10 NBOMe compounds in urine. This GC-MS method was then applied to 8 authentic samples with concentrations compared to those originally identified by NMS laboratories. The rapid influx of NPSs has resulted in the re-analysis of samples and thus, the stability of these substances is crucial information. The stability of mephedrone was investigated, examining the effect that storage temperatures and preservatives had on analyte stability daily for 1 week and then weekly for 10 weeks. Several laboratories identified NPSs use through the cross-reactivity of these substances with existing screening protocols such as ELISA. The application of Immunalysis ketamine, methamphetamine and amphetamine ELISA kits for the detection of NPS was evaluated. The aim of this work was to determine if any cross-reactivity from NPS substances was observed, and to determine whether these existing kits would identify NPS use within biological samples. The cross- reactivity of methoxetamine, 3-MeO-PCE and 3-MeO-PCP for different commercially point of care test (POCT) was also assessed for urine. One of the newest groups of compounds to appear on the NPS market is the NBOMe series. These drugs pose a serious threat to public health due to their high potency, with fatalities already reported in the literature. These compounds are falsely marketed as LSD which increases the chance of adverse effects due to the potency differences between these 2 substances. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was validated in accordance with SWGTOX 2013 guidelines for the detection for 25B, 25C and 25I-NBOMe in urine and hair. Long-Evans rats were administered 25B-, 25C- and 25I-NBOMe at doses ranging from 30-300 µg/kg over a period of 10 days. Tail flick tests were then carried out on the rats in order to determine whether any analgesic effects were observed as a result of dosing. Rats were also shaved prior to their first dose and reshaved after the 10-day period. Hair was separated by colour (black and white) and analysed using the validated LC-MS/MS method, assessing the impact hair colour has on the incorporation of these drugs. Urine was collected from the rats, analysed using the validated LC-MS/MS method and screened for potential metabolites using both LC-MS/MS and quadrupole time of flight (QToF) instrumentation.

Development of paper-based color test-strip for drug detection in aquatic environment: Application to oxytetracycline

The wide use of antibiotics in aquaculture has led to the emergence of resistant microbial species. It should be avoided/minimized by controlling the amount of drug employed in fish farming. For this purpose, the present work proposes test-strip papers aiming at the detection/semi-quantitative determination of organic drugs by visual comparison of color changes, in a similar analytical procedure to that of pH monitoring by universal pH paper. This is done by establishing suitable chemical changes upon cellulose, attributing the paper the ability to react with the organic drug and to produce a color change. Quantitative data is also enabled by taking a picture and applying a suitable mathematical treatment to the color coordinates given by the HSL system used by windows. As proof of concept, this approach was applied to oxytetracycline (OXY), one of the antibiotics frequently used in aquaculture. A bottom-up modification of paper was established, starting by the reaction of the glucose moieties on the paper with 3-triethoxysilylpropylamine (APTES). The so-formed amine layer allowed binding to a metal ion by coordination chemistry, while the metal ion reacted after with the drug to produce a colored compound. The most suitable metals to carry out such modification were selected by bulk studies, and the several stages of the paper modification were optimized to produce an intense color change against the concentration of the drug. The paper strips were applied to the analysis of spiked environmental water, allowing a quantitative determination for OXY concentrations as low as 30 ng/mL. In general, this work provided a simple, method to screen and discriminate tetracycline drugs, in aquaculture, being a promising tool for local, quick and cheap monitoring of drugs.

Uncertainties in projecting climate-change impacts in marine ecosystems

Projections of the impacts of climate change on marine ecosystems are a key prerequisite for the planning of adaptation strategies, yet they are inevitably associated with uncertainty. Identifying, quantifying, and communicating this uncertainty is key to both evaluating the risk associated with a projection and building confidence in its robustness. We review how uncertainties in such projections are handled in marine science. We employ an approach developed in climate modelling by breaking uncertainty down into (i) structural (model) uncertainty, (ii) initialization and internal variability uncertainty, (iii) parametric uncertainty, and (iv) scenario uncertainty. For each uncertainty type, we then examine the current state-of-the-art in assessing and quantifying its relative importance. We consider whether the marine scientific community has addressed these types of uncertainty sufficiently and highlight the opportunities and challenges associated with doing a better job. We find that even within a relatively small field such as marine science, there are substantial differences between subdisciplines in the degree of attention given to each type of uncertainty. We find that initialization uncertainty is rarely treated explicitly and reducing this type of uncertainty may deliver gains on the seasonal-to-decadal time-scale. We conclude that all parts of marine science could benefit from a greater exchange of ideas, particularly concerning such a universal problem such as the treatment of uncertainty. Finally, marine science should strive to reach the point where scenario uncertainty is the dominant uncertainty in our projections.

Development of an electrochemical biosensor for the detection of miRNA-155 in Breast Cancer

Breast cancer is one of the most prevalent forms of cancer in women. Despite all recent advances in early diagnosis and therapy, mortality data is not decreasing. This is an outcome of the inexistence of validated serum biomarkers allowing an early prognosis, out coming from the limited understanding of the natural history of the disease. In this context, miRNAs have been attracting a special interest throughout the scientific community as promising biomarkers in the early diagnosis of cancer. In breast cancer, several miRNAs and their levels of expression are significantly different between normal tissue and tissue with neoplasia, as well as between different molecular subtypes of breast cancer, also associated with prognosis. Thus, this these presents a meta-analysis that allows identifying a reliable miRNA biomarker for the early detection of breast cancer. In this, miRNA-155 was identified as the best one and an electrochemical biosensor was developed for its detection in serum samples. The biosensor was assembled by following three button-up stages: (1) the complementary miRNA sequence thiol terminated (anti-miRNA-155) was immobilized on a commercial gold screen-printed electrode (Au-SPE), followed by (2) blocking non-specific binding with mercaptosuccinic acid and by (3) miRNA hybridization. The biosensor was able to detect miRNA concentrations lying in the 10-18 mol/L (aM) range, displaying a linear response from 10 aM to 1nM. The device showed a limit of detection of 5.7 aM in human serum samples and good selectivity against other biomolecules in serum, such as cancer antigen CA-15.3 and bovine serum albumin (BSA). Overall, this simple and sensitive strategy is a promising approach for the quantitative and/or simultaneous analysis of multiple miRNA in physiological fluids, aiming at further biomedical research devoted to biomarker monitoring and point-of-care diagnosis.

Wind turbine indirect ice detection and operational analysis

Wind energy is one of the most promising and fast growing sector of energy production. Wind is ecologically friendly and relatively cheap energy resource available for development in practically all corners of the world (where only the wind blows). Today wind power gained broad development in the Scandinavian countries. Three important challenges concerning sustainable development, i.e. energy security, climate change and energy access make a compelling case for large-scale utilization of wind energy. In Finland, according to the climate and energy strategy, accepted in 2008, the total consumption of electricity generated by means of wind farms by 2020, should reach 6 - 7% of total consumption in the country [1]. The main challenges associated with wind energy production are harsh operational conditions that often accompany the turbine operation in the climatic conditions of the north and poor accessibility for maintenance and service. One of the major problems that require a solution is the icing of turbine structures. Icing reduces the performance of wind turbines, which in the conditions of a long cold period, can significantly affect the reliability of power supply. In order to predict and control power performance, the process of ice accretion has to be carefully tracked. There are two ways to detect icing – directly or indirectly. The first way applies to the special ice detection instruments. The second one is using indirect characteristics of turbine performance. One of such indirect methods for ice detection and power loss estimation has been proposed and used in this paper. The results were compared to the results directly gained from the ice sensors. The data used was measured in Muukko wind farm, southeast Finland during a project 'Wind power in cold climate and complex terrain'. The project was carried out in 9/2013 - 8/2015 with the partners Lappeenranta university of technology, Alstom renovables España S.L., TuuliMuukko, and TuuliSaimaa.

MICROFLUIDIC ASSAY PERFORMANCE ENHANCEMENT USING POROUS VOLUMETRIC DETECTION ELEMENTS FOR IMPEDEMETRIC AND OPTICAL SENSING

Microfluidic technologies have great potential to help create automated, cost-effective, portable devices for rapid point of care (POC) diagnostics in diverse patient settings. Unfortunately commercialization is currently constrained by the materials, reagents, and instrumentation required and detection element performance. While most microfluidic studies utilize planar detection elements, this dissertation demonstrates the utility of porous volumetric detection elements to improve detection sensitivity and reduce assay times. Impedemetric immunoassays were performed utilizing silver enhanced gold nanoparticle immunoconjugates (AuIgGs) and porous polymer monolith or silica bead bed detection elements within a thermoplastic microchannel. For a direct assay with 10 µm spaced electrodes the detection limit was 0.13 fM AuIgG with a 3 log dynamic range. The same assay was performed with electrode spacing of 15, 40, and 100 µm with no significant difference between configurations. For a sandwich assay the detection limit was10 ng/mL with a 4 log dynamic range. While most impedemetric assays rely on expensive high resolution electrodes to enhance planar senor performance, this study demonstrates the employment of porous volumetric detection elements to achieve similar performance using lower resolution electrodes and shorter incubation times. Optical immunoassays were performed using porous volumetric capture elements perfused with refractive index matching solutions to limit light scattering and enhance signal. First, fluorescence signal enhancement was demonstrated with a porous polymer monolith within a silica capillary. Next, transmission enhancement of a direct assay was demonstrated by infusing aqueous sucrose solutions through silica bead beds with captured silver enhanced AuIgGs yielding a detection limit of 0.1 ng/mL and a 5 log dynamic range. Finally, ex situ functionalized porous silica monolith segments were integrated into thermoplastic channels for a reflectance based sandwich assay yielding a detection limit of 1 ng/mL and a 5 log dynamic range. The simple techniques for optical signal enhancement and ex situ element integration enable development of sensitive, multiplexed microfluidic sensors. Collectively the demonstrated experiments validate the use of porous volumetric detection elements to enhance impedemetric and optical microfluidic assays. The techniques rely on commercial reagents, materials compatible with manufacturing, and measurement instrumentation adaptable to POC diagnostics.

Integración de dispositivos electrónicos inteligentes en Smart Grid

El sector eléctrico está experimentando cambios importantes tanto a nivel de gestión como a nivel de mercado. Una de las claves que están acelerando este cambio es la penetración cada vez mayor de los Sistemas de Generación Distribuida (DER), que están dando un mayor protagonismo al usuario a la hora de plantear la gestión del sistema eléctrico. La complejidad del escenario que se prevé en un futuro próximo, exige que los equipos de la red tenga la capacidad de interactuar en un sistema mucho más dinámico que en el presente, donde la interfaz de conexión deberá estar dotada de la inteligencia necesaria y capacidad de comunicación para que todo el sistema pueda ser gestionado en su conjunto de manera eficaz. En la actualidad estamos siendo testigos de la transición desde el modelo de sistema eléctrico tradicional hacia un nuevo sistema, activo e inteligente, que se conoce como Smart Grid. En esta tesis se presenta el estudio de un Dispositivo Electrónico Inteligente (IED) orientado a aportar soluciones para las necesidades que la evolución del sistema eléctrico requiere, que sea capaz de integrase en el equipamiento actual y futuro de la red, aportando funcionalidades y por tanto valor añadido a estos sistemas. Para situar las necesidades de estos IED se ha llevado a cabo un amplio estudio de antecedentes, comenzando por analizar la evolución histórica de estos sistemas, las características de la interconexión eléctrica que han de controlar, las diversas funciones y soluciones que deben aportar, llegando finalmente a una revisión del estado del arte actual. Dentro de estos antecedentes, también se lleva a cabo una revisión normativa, a nivel internacional y nacional, necesaria para situarse desde el punto de vista de los distintos requerimientos que deben cumplir estos dispositivos. A continuación se exponen las especificaciones y consideraciones necesarias para su diseño, así como su arquitectura multifuncional. En este punto del trabajo, se proponen algunos enfoques originales en el diseño, relacionados con la arquitectura del IED y cómo deben sincronizarse los datos, dependiendo de la naturaleza de los eventos y las distintas funcionalidades. El desarrollo del sistema continua con el diseño de los diferentes subsistemas que lo componen, donde se presentan algunos algoritmos novedosos, como el enfoque del sistema anti-islanding con detección múltiple ponderada. Diseñada la arquitectura y funciones del IED, se expone el desarrollo de un prototipo basado en una plataforma hardware. Para ello se analizan los requisitos necesarios que debe tener, y se justifica la elección de una plataforma embebida de altas prestaciones que incluye un procesador y una FPGA. El prototipo desarrollado se somete a un protocolo de pruebas de Clase A, según las normas IEC 61000-4-30 e IEC 62586-2, para comprobar la monitorización de parámetros. También se presentan diversas pruebas en las que se han estimado los retardos implicados en los algoritmos relacionados con las protecciones. Finalmente se comenta un escenario de prueba real, dentro del contexto de un proyecto del Plan Nacional de Investigación, donde este prototipo ha sido integrado en un inversor dotándole de la inteligencia necesaria para un futuro contexto Smart Grid.

Contextualising change through a common strategy

European universities are currently going through a process of change in order to meet the common goals set for higher education by the European Commission. They are revising their educational models to adjust them to the guidelines of the ‘‘Bologna Process’’ and are devising an institutional strategy for its implementation. In practical terms, this means aligning former national degrees and diplomas to standard European Bachelor and Masters degrees and PhD doctorates, by creating acknowledged professional qualification benchmarks that also include adjusted course lengths and contents. This process, in the end, mostly affects academic staff members who have a fundamental role to play in carrying out the pedagogical reforms on the teaching front. Besides presenting a commentary on the institutional approach of one particular technical university in Spain, the purpose of this paper is to propose, from the authors’ point of view as lecturers, a strategy which has the potential to create a favourable atmosphere for carrying out such a reform. The article’s main objective is to highlight a series of action points which may serve to reinforce and advance the main institutional strategy by relying on the powerful influence of its academic staff members

Climate change and impacts on family farming in the North and Northeast of Brazil.

The starting point for this study was the consideration of future climate change scenarios and their uncertainties. The paper presents the global projections from the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) and compares them with regional scenarios (downscaling) developed by the Brazilian National Institute for Space Research (Instituto Nacional de Pesquisas Espaciais - INPE), with a focus on two main IPCC scenarios (RCP4.5 and RCP8.5) and two main global models (MIROC and Hadley Centre) for the periods 2011-2040 and 2041-2070. It aims to identify the main trends in terms of changes in temperature and precipitation for the North and Northeast regions of Brazil (more specifically, in the Amazon, semi-arid and cerrado biomes).

Two roads to planet detection

One of the most exciting discoveries in astrophysics of the last last decade is of the sheer diversity of planetary systems. These include "hot Jupiters", giant planets so close to their host stars that they orbit once every few days; "Super-Earths", planets with sizes intermediate to those of Earth and Neptune, of which no analogs exist in our own solar system; multi-planet systems with planets smaller than Mars to larger than Jupiter; planets orbiting binary stars; free-floating planets flying through the emptiness of space without any star; even planets orbiting pulsars. Despite these remarkable discoveries, the field is still young, and there are many areas about which precious little is known. In particular, we don't know the planets orbiting Sun-like stars nearest to our own solar system, and we know very little about the compositions of extrasolar planets. This thesis provides developments in those directions, through two instrumentation projects.

The first chapter of this thesis concerns detecting planets in the Solar neighborhood using precision stellar radial velocities, also known as the Doppler technique. We present an analysis determining the most efficient way to detect planets considering factors such as spectral type, wavelengths of observation, spectrograph resolution, observing time, and instrumental sensitivity. We show that G and K dwarfs observed at 400-600 nm are the best targets for surveys complete down to a given planet mass and out to a specified orbital period. Overall we find that M dwarfs observed at 700-800 nm are the best targets for habitable-zone planets, particularly when including the effects of systematic noise floors caused by instrumental imperfections. Somewhat surprisingly, we demonstrate that a modestly sized observatory, with a dedicated observing program, is up to the task of discovering such planets.

We present just such an observatory in the second chapter, called the "MINiature Exoplanet Radial Velocity Array," or MINERVA. We describe the design, which uses a novel multi-aperture approach to increase stability and performance through lower system etendue, as well as keeping costs and time to deployment down. We present calculations of the expected planet yield, and data showing the system performance from our testing and development of the system at Caltech's campus. We also present the motivation, design, and performance of a fiber coupling system for the array, critical for efficiently and reliably bringing light from the telescopes to the spectrograph. We finish by presenting the current status of MINERVA, operational at Mt. Hopkins observatory in Arizona.

The second part of this thesis concerns a very different method of planet detection, direct imaging, which involves discovery and characterization of planets by collecting and analyzing their light. Directly analyzing planetary light is the most promising way to study their atmospheres, formation histories, and compositions. Direct imaging is extremely challenging, as it requires a high performance adaptive optics system to unblur the point-spread function of the parent star through the atmosphere, a coronagraph to suppress stellar diffraction, and image post-processing to remove non-common path "speckle" aberrations that can overwhelm any planetary companions.

To this end, we present the "Stellar Double Coronagraph," or SDC, a flexible coronagraphic platform for use with the 200" Hale telescope. It has two focal and pupil planes, allowing for a number of different observing modes, including multiple vortex phase masks in series for improved contrast and inner working angle behind the obscured aperture of the telescope. We present the motivation, design, performance, and data reduction pipeline of the instrument. In the following chapter, we present some early science results, including the first image of a companion to the star delta Andromeda, which had been previously hypothesized but never seen.

A further chapter presents a wavefront control code developed for the instrument, using the technique of "speckle nulling," which can remove optical aberrations from the system using the deformable mirror of the adaptive optics system. This code allows for improved contrast and inner working angles, and was written in a modular style so as to be portable to other high contrast imaging platforms. We present its performance on optical, near-infrared, and thermal infrared instruments on the Palomar and Keck telescopes, showing how it can improve contrasts by a factor of a few in less than ten iterations.

One of the large challenges in direct imaging is sensing and correcting the electric field in the focal plane to remove scattered light that can be much brighter than any planets. In the last chapter, we present a new method of focal-plane wavefront sensing, combining a coronagraph with a simple phase-shifting interferometer. We present its design and implementation on the Stellar Double Coronagraph, demonstrating its ability to create regions of high contrast by measuring and correcting for optical aberrations in the focal plane. Finally, we derive how it is possible to use the same hardware to distinguish companions from speckle errors using the principles of optical coherence. We present results observing the brown dwarf HD 49197b, demonstrating the ability to detect it despite it being buried in the speckle noise floor. We believe this is the first detection of a substellar companion using the coherence properties of light.

Electrochemical Immunosensing of Cortisol in an Automated Microfluidic System Towards Point-of-Care Applications

This dissertation describes the development of a label-free, electrochemical immunosensing platform integrated into a low-cost microfluidic system for the sensitive, selective and accurate detection of cortisol, a steroid hormone co-related with many physiological disorders. Abnormal levels of cortisol is indicative of conditions such as Cushing’s syndrome, Addison’s disease, adrenal insufficiencies and more recently post-traumatic stress disorder (PTSD). Electrochemical detection of immuno-complex formation is utilized for the sensitive detection of Cortisol using Anti-Cortisol antibodies immobilized on sensing electrodes. Electrochemical detection techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) have been utilized for the characterization and sensing of the label-free detection of Cortisol. The utilization of nanomaterial’s as the immobilizing matrix for Anti-cortisol antibodies that leads to improved sensor response has been explored. A hybrid nano-composite of Polyanaline-Ag/AgO film has been fabricated onto Au substrate using electrophoretic deposition for the preparation of electrochemical immunosening of cortisol. Using a conventional 3-electrode electrochemical cell, a linear sensing range of 1pM to 1µM at a sensitivity of 66µA/M and detection limit of 0.64pg/mL has been demonstrated for detection of cortisol. Alternately, a self-assembled monolayer (SAM) of dithiobis(succinimidylpropionte) (DTSP) has been fabricated for the modification of sensing electrode to immobilize with Anti-Cortisol antibodies. To increase the sensitivity at lower detection limit and to develop a point-of-care sensing platform, the DTSP-SAM has been fabricated on micromachined interdigitated microelectrodes (µIDE). Detection of cortisol is demonstrated at a sensitivity of 20.7µA/M and detection limit of 10pg/mL for a linear sensing range of 10pM to 200nM using the µIDE’s. A simple, low-cost microfluidic system is designed using low-temperature co-fired ceramics (LTCC) technology for the integration of the electrochemical cortisol immunosensor and automation of the immunoassay. For the first time, the non-specific adsorption of analyte on LTCC has been characterized for microfluidic applications. The design, fabrication technique and fluidic characterization of the immunoassay are presented. The DTSP-SAM based electrochemical immunosensor on µIDE is integrated into the LTCC microfluidic system and cortisol detection is achieved in the microfluidic system in a fully automated assay. The fully automated microfluidic immunosensor hold great promise for accurate, sensitive detection of cortisol in point-of-care applications.

The Economics of Adaptation to Climate Change in Coasts and Oceans: Literature Review, Policy Implications and Research Agenda

Sea level rise and other effects of climate change on oceans and coasts around the world are major reasons to halt the emissions of greenhouse gases to the maximum extent. But historical emissions and sea level rise have already begun so steps to adapt to a world where shorelines, coastal populations, and economies could be dramatically altered are now essential. This presents significant economic challenges in four areas. (1) Large expenditures for adaptation steps may be required but the extent of sea level rise and thus the expenditures are unknowable at this point. Traditional methods for comparing benefits and costs are severely limited, but decisions must still be made. (2) It is not clear where the funding for adaptation will come from, which is a barrier to even starting planning. (3) The extent of economic vulnerability has been illustrated with assessments of risks to current properties, but these likely significantly understate the risks that lie in the future. (4) Market-based solutions to reducing climate change are now generally accepted, but their role in adaptation is less clear. Reviewing the literature addressing each of these points, this paper suggests specific strategies for dealing with uncertainty in assessing the economics of adaptation options, reviews the wide range of options for funding coastal adaption, identifies a number of serious deficiencies in current economic vulnerability studies, and suggests how market based approaches might be used in shaping adaptation strategies. The paper concludes by identifying a research agenda for the economics of coastal adaptation that, if completed, could significantly increase the likelihood of economically efficient coastal adaptation.

Diachronic and Synchronic Indexing: Modeling Conceptual Change in Indexing Languages

This paper outlines a model of conceptual change in indexing languages. Findings from this modeling effort point to three ways meaning and relationships are established and then change in an indexing language. These ways: structural, terminological, and textual point to ways indexing language metadata can aid in managing conceptual change in indexing languages.

Regional variation and change in the history of English strong verbs

This thesis investigates how the strong verb system inherited from Old English evolved in the regional dialects of Middle English (ca. 1100-1500). Old English texts preserve a relatively complex system of strong verbs, in which traditionally seven different ablaut classes are distinguished. This system becomes seriously disrupted from the Late Old English and Early Middle English periods onwards. As a result, many strong verbs die out, or have their ablaut patterns affected by sound change and morphological analogy, or transfer to the weak conjugation. In my thesis, I study the beginnings of two of these developments in two strong verb classes to find out what the evidence from Middle English regional dialects can tell us about their origins and diffusion. Chapter 2 concentrates on the strong-to-weak shift in Class III verbs, and investigates to what extent strong, mixed and weak past tense and participle forms vary in Middle English dialects, and whether the variation is more pronounced in the paradigms of specific verbs or sub-classes. Chapter 3 analyses the regional distribution of ablaut levelling in strong Class IV verbs throughout the Middle English period. The Class III and IV data for the Early Middle English period are drawn from A Linguistic Atlas of Early Middle English, and the data for the Late Middle English period from a sub-corpus of files from The Penn-Helsinki Parsed Corpus of Middle English and The Middle English Grammar Corpus. Furthermore, The English Dialect Dictionary and Grammar are consulted as an additional reference point to find out to what extent the Middle English developments are reflected in Late Modern English dialects. Finally, referring to modern insights into language variation and change and linguistic interference, Chapter 4 discusses to what extent intra- and extra-linguistc factors, such as token and type frequency, stem structure and language contact, might correlate with the strong-to-weak shift and ablaut levelling in Class III and IV verbs in the Middle English period. The thesis is accompanied by six appendices that contain further information about my distinction of Middle English dialect areas (Appendix A), historical Class III and IV verbs (B and C) and the text samples and linguistic data from the Middle English text corpora (D, E and F).

Handgrip strength cut-off for cardiometabolic risk index among Colombian children and adolescents : the FUPRECOL study

Abstract Objective: Evidence shows an association between muscular strength (MS) and health among youth, however low muscular strength cut-points for the detection of high metabolic risk in Latin-American populations are scarce. The aim of this study was two-fold: to explore potential age- and sex-specific thresholds of MS, for optimal cardiometabolic risk categorization among Colombian children and adolescents; and to investigate if cardiometabolic risk differed by MS group by applying the receiver operating characteristic curve (ROC) cut point. Methods: This is a secondary analysis of a cross-sectional study (the FUPRECOL study), published elsewhere. The FUPRECOL study assessments were conducted during the 2014– 2015 school year. MS was estimated by a handle dynamometer on 1,950 children and adolescents from Colombia, using the MS relative to weight (handgrip strength/body mass). A metabolic risk score was computed from the following components: waist circumference, triglycerides, HDL-c, glucose, systolic and diastolic blood pressure. ROC analysis showed a significant discriminatory accuracy of MS in identifying the low/high metabolic risk in children and adolescents and both gender. Results: In children, handgrip strength/body mass level for a low metabolic risk were 0.359 and 0.376 in girls and boys, respectively. In adolescents, these points were 0.440 and 0.447 in girls and boys, respectively. Conclusion: In conclusion, the results suggest a hypothetical MS level relative to weight for having a low metabolic risk, which could be used to identify youths at risk.