A Fuzzy k-Nearest Neighbors Classifier to Deal with Imperfect Data

© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in Soft Computing. To access the final edited and published work see https://doi.org/10.1007/s00500-017-2567-xThe k-nearest neighbors method (kNN) is a nonparametric, instance-based method used for regression and classification. To classify a new instance, the kNN method computes its k nearest neighbors and generates a class value from them. Usually, this method requires that the information available in the datasets be precise and accurate, except for the existence of missing values. However, data imperfection is inevitable when dealing with real-world scenarios. In this paper, we present the kNNimp classifier, a k-nearest neighbors method to perform classification from datasets with imperfect value. The importance of each neighbor in the output decision is based on relative distance and its degree of imperfection. Furthermore, by using external parameters, the classifier enables us to define the maximum allowed imperfection, and to decide if the final output could be derived solely from the greatest weight class (the best class) or from the best class and a weighted combination of the closest classes to the best one. To test the proposed method, we performed several experiments with both synthetic and realworld datasets with imperfect data. The results, validated through statistical tests, show that the kNNimp classifier is robust when working with imperfect data and maintains a good performance when compared with other methods in the literature, applied to datasets with or without imperfection

Evidence-based vaccinology: supporting evidence-informed considerations to introduce routine hepatitis A immunization in South Africa

Hepatitis A is a vaccine preventable disease caused by the Hepatitis A Virus (HAV). Currently, South Africa is classified by the World Health Organization (WHO) as a high hepatitis A endemic region where 90% of children are assumed to be “naturally immunised” following HAV exposure before the age of 10 years old. In high hepatitis A endemic settings, routine vaccination against HAV is not necessary due to high rates of “natural immunization”. Recent data suggest a possible shift from high to intermediate HAV endemicity may be occurring in South Africa. Countries with intermediate HAV endemicity and no routine hepatitis A vaccination program have a high risk of experiencing hepatitis A outbreaks and high costs associated with care. Currently, there is no routine vaccination program against HAV in South Africa. The aim of this PhD was to generate evidence for decision making on whether a routine vaccination program against HAV should be considered for introduction into the South African Expanded Program on Immunizations (EPI-SA). The objectives included gathering context-specific evidence on the epidemiologic features of hepatitis A, clinical characteristics of the disease, hepatitis A vaccine characteristics and cost of case management. Using this evidence, the PhD estimated the future epidemiology of hepatitis A and impacts of routine hepatitis A vaccination scenarios in the country. The PhD's overall methods were informed by the principles of Evidence-Based Vaccinology for developing vaccine recommendations. The project included a mixed-methods approach: systematic reviews, a retrospective clinical folder review, mathematical modelling, and economic evaluation. A dynamic transmission model was built to forecast the future epidemiology of hepatitis A and to simulate the impacts of several different childhood hepatitis A vaccination strategies in South Africa. Selected findings have been published in relevant peer-reviewed journals. In addition, a technical dossier was prepared to submit to the South African National Advisory Group on Immunization (NAGI) on behalf of the Hepatitis A Working Group for considerations of introducing hepatitis A vaccination into the South African EPI

The landscape of the nucleocytoplasmic transport system and cell-type specific variations of the nuclear pore complex

The main function of the nuclear pore complex (NPC) is to facilitate and regulate the transport between the cytosol and the nucleus but NPCs are also involved in various other cellular functions, including regulation of gene expression, translational control, signal transduction and cell differentiation. The nucleocytoplasmic transport system is composed of the NPC, that forms a large aqueous channel lined with FG-repeats containing nucleoporins (FG-Nups). FG-Nups constitute a permeability barrier, which prevents the passage of the majority of all proteins. Nuclear transport receptors (NTRs, also called importins, exportins or karyopherins) specifically recognize localization signals of cargo molecules and facilitate their passage through the central channel by transiently interacting with FG-Nups. Classical methods such as affinity purification or measurement of dissociation constants are not well-suited to globally identify NTR-cargo interactions because they are of a very transient nature, the spectrum of recognized cargos is huge and their dynamic concentration range comprises orders of magnitude. The exact cargo spectrum of the majority of NTRs, their specificity and even the extent to which active nucleocytoplasmic transport contributes to protein localization thus remains uncertain. To systematically map cargo-NTR relationships in an unbiased way in situ, I used proximity labeling mass spectrometry based on the so-called BioID system. I systematically fused BirA to various NTRs and other factors involved in nucleocytoplasmic transport. I found that at least one third of the human proteome is subject to active nuclear transport. I characterized the specific cargo spectrum of several NTRs and can thus estimate their specificity or overlap with other transport pathways. I identified the responsible transport pathways of various key protein complexes and demonstrated that those and components of pathways tend to be transported by related NTRs. The identification of the exact biotinylation sites provided evidence for the relevant interaction surfaces and sheds light in direct versus piggyback transport mechanisms. To understand the compositional changes, potentially affecting the nucleocytoplasmic transport, within the NPC and NTR system better, I investigated them during development and within different cell types in Drosophila and Zebrafish. For the NPC only Nups, exposed to the environment, showed significant changes. The abundance changes of the NTRs were more dynamic and indicated a more flexible adaptation to changing circumstances

Advanced manufacturing techniques for X-ray and VHE gamma-ray astronomical mirrors.

The main theme of this thesis is on the development of the technologies for the future X-ray astronomy telescopes and specifically for the New Hard X-ray Mission and eROSITA (Spectrum-RG) missions. Other important next future X-ray missions, currently under advanced study and/or manufacturing are NuSTAR (USA), ASTRO-H (Japan) and GEMS (USA). The New Hard X-ray Mission (NHXM) is being developed in Italy as an evolution of the original HEXIT-SAT project and is now the hard x-ray project of reference for the Italian high energy community. NHXM is meant to provide a real breakthrough on a number of hot astrophysical issues, by exploiting the most advanced technology in broad-band (0.2 \u2013 80 keV) high angular resolution (<20 arc seconds HEW) grazing incidence mirrors and spectroscopic detectors, together with the use of a high efficiency imaging polarimeter. Such issues can be summarized in two main headings: \u25cf making the census of the population of black holes in the Universe and probing the physics of accretion in the most diverse conditions; \u25cf investigating the particle acceleration mechanisms at work in different contexts, and the effects of radiative transfer in highly magnetized plasmas and strong gravitational fields. These topics were identified as top priority in the study commissioned by the Italian Space Agency (ASI) in 2004 to the Italian scientific community with contracts involving Thales-Alenia Space Italy (TAS-I, Turin), the Media Lario Technologies (MLT, Lecco) company and the INAF institution. NHXM benefits from the phase A study of the canceled French-Italian-German SIMBOL-X mission (2007-2008) and has been recently subjected to a scientific phase B study financed by ASI. Media Lario Technologies company received a contract from ASI in 2009 for a Technology Development Program (ASI-TDP) aiming at improving the technology readiness level with also in-house adoption of hardware for the metrology/manufacturing of the multilayer x-ray optics. Spectrum-RG is a Russian - German x-ray astrophysical observatory scheduled for lunch in 2013. German Space Agency (DLR) is responsible for the development of the key mission instrument - the x-ray grazing incident mirror telescope eROSITA. The second experiment is ART-XC - an x-ray mirror telescope with a harder response than eROSITA, which is being developed by Russia (IKI, Moscow and VNIIEF, Sarov). The name eROSITA stands for extended Roentgen Survey with an Imaging Telescope Array. The general design of the eROSITA x-ray telescope is derived from that of ABRIXAS: a bundle of 7 mirror modules with short focal lengths make up a compact telescope which is ideal for survey observations. Similar designs had been proposed for the missions DUO and ROSITA but were not realized. Compared to those, however, the effective area in the soft x-ray band has now much increased by adding 27 additional outer mirror shells to the original 27 ones of each mirror module. The requirement on the on-axis resolution has also been confined, namely to 15 arc seconds HEW. For these reasons the prefix \u201cextended\u201d to the original name \u201cROSITA\u201d had been added. The scientific motivation for this extension is founded in the ambitious goal to detect about 100000 clusters of galaxies which trace the large scale structure of the Universe in space and time. The main scientific goals are: \u25cf to detect the hot intergalactic medium of 50-100 thousand galaxy clusters and groups and hot gas in filaments between clusters to map out the large scale structure in the Universe for the study of cosmic structure evolution; \u25cf to detect systematically all obscured accreting Black Holes in nearby galaxies and many (up to 3 Million) new, distant active galactic nuclei; \u25cf to study in detail the physics of galactic x-ray source populations, like pre-main sequence stars, supernova remnants and x-ray binaries. Max-Planck-Institute f\ufcr extraterrestrische Physik (MPE) is the scientific institute responsible for the eROSITA Payload. Media Lario Technologies (MLT) is the industrial enabler for the manufacturing of the Optical Payload for eROSITA - including the flight quality mandrels, and it is currently in the C/D Phase of the project. The research activity described in this thesis has been carried out at Media Lario Technologies company and at the Brera Astronomical Observatory under the supervision of INAF-OAB researchers Dott. Giovanni Pareschi and Dott. Gianpiero Tagliaferri. The research activity of the author of this thesis is focused on the development of an advance polishing technique for the mandrels to be used as masters in the mirrors replication by electroforming. The goal is to implement a process where the mandrels can be manufactured with a high accuracy (< 6 arc seconds HEW) and low roughness (< 0.2 nm rms) within a consistent short time. In the contest of the eROSITA and NHXM (projects currently running in MLT) the author participated as technical/scientific responsible, investigating innovative mandrels manufacturing technologies (e.g. Single Point Diamond Turning, shape corrective polishing) representing an evolution of the standard approach used so far. In this frame the author has also contributed to the adoption of a customized deterministic polishing machine and a customized 3D metrology device for the mandrel geometrical characterization. An additional research activity, performed by the author at Media Lario Technologies company and at the Brera Astronomical Observatory, is focused on the development of lightweight glass mirrors manufactured via cold-slumping technique for Imaging Atmospheric Cherenkov Telescopes (IACT). Very High Energy (VHE) gamma rays, with photon energies in the TeV range, can be detected by ground based experiments. In fact, such high energy photons interact high in the upper atmosphere and generate an air shower of secondary particles. These particles emit the so-called Cherenkov light, a faint blue light. The mirror elements here developed have a sandwich-like structure where the reflecting and backing facets are composed by glass sheets with an interposed honeycomb aluminum core. This effort found application at the world\u2019s largest IACT, the 17m MAGIC II telescope (currently operating in Roque de los Muchachos - La Palma, Canary Islands), where 112 mirrors (~ 1 squared meter each), manufactured with the newly developed cold-slumping technique here described, are installed

Asenapine versus placebo for schizophrenia

Background Background Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. Objectives Objectives To determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo. Search methods Search methods We searched the Cochrane Schizophrenia Group's Trials Register (July 04, 2014) which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitation for inclusion of records into the register. We inspected references of all included studies for further relevant studies. Selection criteria Selection criteria Our review includes randomised controlled trials (RCTs) comparing asenapine with placebo in adults (however defined) with schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder and delusional disorder, again, by any means of diagnosis. Data collection and analysis Data collection and analysis We inspected citations from the searches and identified relevant abstracts, and extracted data from all included studies. For binary data we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous data we calculated mean differences (MD). We used the GRADE approach to produce a 'Summary of findings' table which included our outcomes of interest, where possible. We used a fixed-effect model for our analyses. Main results Main results We obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short-term amongst people receiving asenapine. People receiving asenapine demonstrated significant reductions in negative symptoms (1 RCT, n = 336, MD -1.10, 95% CI -2.29 to 0.09, very low-quality evidence) at short-term. Individuals receiving asenapine demonstrated significantly fewer incidents of serious adverse effects (1 RCT, n = 386, RR 0.29, 95% CI 0.14 to 0.63, very low-quality evidence) at medium-term. There was no clear difference in people discontinuing the study for any reason between asenapine and placebo at short-term (5 RCTs, n = 1046, RR 0.91, 95% CI 0.80 to 1.04, very low-quality evidence). No trial reported data for extrapyramidal symptoms or costs. Authors' conclusions Authors' conclusions There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst minimising the risk of adverse effects. However due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. We identify a need for large-scale, longer-term, better-designed and conducted randomised controlled trials investigating the clinical effects and safety of asenapine

Advancing Medical Technology for Motor Impairment Rehabilitation: Tools, Protocols, and Devices

Excellent motor control skills are necessary to live a high-quality life. Activities such as walking, getting dressed, and feeding yourself may seem mundane, but injuries to the neuromuscular system can render these tasks difficult or even impossible to accomplish without assistance. Statistics indicate that well over 100 million people are affected by diseases or injuries, such as stroke, Parkinson’s Disease, Multiple Sclerosis, Cerebral Palsy, peripheral nerve injury, spinal cord injury, and amputation, that negatively impact their motor abilities. This wide array of injuries presents a challenge to the medical field as optimal treatment paradigms are often difficult to implement due to a lack of availability of appropriate assessment tools, the inability for people to access the appropriate medical centers for treatment, or altogether gaps in technology for treating the underlying impairments causing the disability. Addressing each of these challenges will improve the treatment of movement impairments, provide more customized and continuous treatment to a larger number of patients, and advance rehabilitative and assistive device technology. In my research, the key approach was to develop tools to assess and treat upper extremity movement impairment. In Chapter 2.1, I challenged a common biomechanical[GV1] modeling technique of the forearm. Comparing joint torque values through inverse dynamics simulation between two modeling platforms, I discovered that representing the forearm as a single cylindrical body was unable to capture the inertial parameters of a physiological forearm which is made up of two segments, the radius and ulna. I split the forearm segment into a proximal and distal segment, with the rationale being that the inertial parameters of the proximal segment could be tuned to those of the ulna and the inertial parameters of the distal segment could be tuned to those of the radius. Results showed a marked increase in joint torque calculation accuracy for those degrees of freedom that are affected by the inertial parameters of the radius and ulna. In Chapter 2.2, an inverse kinematic upper extremity model was developed for joint angle calculations from experimental motion capture data, with the rationale being that this would create an easy-to-use tool for clinicians and researchers to process their data. The results show accurate angle calculations when compared to algebraic solutions. Together, these chapters provide easy-to-use models and tools for processing movement assessment data. In Chapter 3.1, I developed a protocol to collect high-quality movement data in a virtual reality task that is used to assess hand function as part of a Box and Block Test. The goal of this chapter is to suggest a method to not only collect quality data in a research setting but can also be adapted for telehealth and at home movement assessment and rehabilitation. Results indicate that the data collected in this protocol are good and the virtual nature of this approach can make it a useful tool for continuous, data driven care in clinic or at home. In Chapter 3.2 I developed a high-density electromyography device for collecting motor unit action potentials of the arm. Traditional surface electromyography is limited by its ability to obtain signals from deep muscles and can also be time consuming to selectively place over appropriate muscles. With this high-density approach, muscle coverage is increased, placement time is decreased, and deep muscle activity can potentially be collected due to the high-density nature of the device[GV2] . Furthermore, the high-density electromyography device is built as a precursor to a high-density electromyography-electrical stimulation device for functional electrical stimulation. The customizable nature of the prototype in Chapter 3.2 allows for the implementation both recording and stimulating electrodes. Furthermore, signal results show that the electromyography data obtained from the device are of high quality and are correlated with gold standard surface electromyography sensors. One key factor in a device that can record and then stimulate based on the information from the recorded signals is an accurate movement intent decoder. High-quality movement decoders have been designed by closed-loop device controllers in the past, but they still struggle when the user interacts with objects of varying weight due to underlying alterations in muscle signals. In Chapter 4, I investigate this phenomenon by administering an experiment where participants perform a Box and Block Task with objects of 3 different weights, 0 kg, 0.02 kg, and 0.1 kg. Electromyography signals of the participants right arm were collected and co-contraction levels between antagonistic muscles were analyzed to uncover alterations in muscle forces and joint dynamics. Results indicated contraction differences between the conditions and also between movement stages (contraction levels before grabbing the block vs after touching the block) for each condition. This work builds a foundation for incorporating object weight estimates into closed-loop electromyography device movement decoders. Overall, we believe the chapters in this thesis provide a basis for increasing availability to movement assessment tools, increasing access to effective movement assessment and rehabilitation, and advance the medical device and technology field

Algorithms for Transcriptome Quantification and Reconstruction from RNA-Seq Data

Massively parallel whole transcriptome sequencing and its ability to generate full transcriptome data at the single transcript level provides a powerful tool with multiple interrelated applications, including transcriptome reconstruction, gene/isoform expression estimation, also known as transcriptome quantification. As a result, whole transcriptome sequencing has become the technology of choice for performing transcriptome analysis, rapidly replacing array-based technologies. The most commonly used transcriptome sequencing protocol, referred to as RNA-Seq, generates short (single or paired) sequencing tags from the ends of randomly generated cDNA fragments. RNA-Seq protocol reduces the sequencing cost and significantly increases data throughput, but is computationally challenging to reconstruct full-length transcripts and accurately estimate their abundances across all cell types. We focus on two main problems in transcriptome data analysis, namely, transcriptome reconstruction and quantification. Transcriptome reconstruction, also referred to as novel isoform discovery, is the problem of reconstructing the transcript sequences from the sequencing data. Reconstruction can be done de novo or it can be assisted by existing genome and transcriptome annotations. Transcriptome quantification refers to the problem of estimating the expression level of each transcript. We present a genome-guided and annotation-guided transcriptome reconstruction methods as well as methods for transcript and gene expression level estimation. Empirical results on both synthetic and real RNA-seq datasets show that the proposed methods improve transcriptome quantification and reconstruction accuracy compared to previous methods

The Cape fur seal : monitoring and management in the Benguela Current ecosystem

Includes abstract.Includes bibliographical references.At the root of this thesis was the Benguela Current Large Marine Ecosystem (BCLME) Programme’s project "Top Predators as Biological Indicators of Ecosystem Change in the BCLME" (LMR/EAF/03/02). The objectives of this project were to assess the utility of top predators as biological indicators of ecosystem change in the Benguela Current Ecosystem, and implement an appropriate, integrated, system-wide monitoring programme based on top predators, to support ecosystem-based management in the Benguela Current Ecosystem

Datenbasierte Ansätze für moderne klinische Risikovorhersagen

In this thesis the use of data scientific approaches in the life sciences is illustrated by means of contemporary prostate cancer risk models. Validation techniques are introduced and analytical confidence intervals for selected methods derived. In addition, diverse regression approaches to incorporate heterogeneous cohorts, an update of an online available risk calculator and machine learning methods are analyzed and compared.In der vorliegenden Arbeit wird der Einsatz von datenbasierten Ansätzen in den Lebenswissenschaften anhand von zeitgemäßen Risikomodellen für Prostatakrebs dargestellt. Validierungstechniken werden eingeführt und analytische Konfidenzintervalle für ausgewählte Methoden hergeleitet. Des Weiteren werden verschiedene Regressionsansätze zur Integration von heterogenen Kohorten, eine Aktualisierung eines online verfügbaren Risikorechners und Methoden des maschinellen Lernens analysiert und verglichen