The clinical utility of the middle latency and 40Hz auditory evoked potentials in audiological electrodiagnosis

The two elcctrophysiological tests currently favoured in the clinical measurement of hearing threshold arc the brainstorm evoked potential (BAEP) and the slow vertex response (SVR). However, both tests possess disadvantages. The BAEP is the test of choice in younger patients as it is stable at all levels of arousal, but little information has been obtained to date at a range of frequencies. The SVR is frequency specific but is unreliable in certain adult subjects and is unstable during sleep or in young children. These deficiencies have prompted research into a third group of potentials, the middle latency response (MLR) and the 40HZ responses. This research has compared the SVR and 40HZ response in waking adults and reports that the 40HZ test can provide a viable alternative to the SVR provided that a high degree of subject relaxation is ensured. A second study examined the morphology of the MLR and 40HZ during sleep. This work suggested that these potentials arc markedly different during sleep and that methodological factors have been responsible for masking these changes in previous studies. The clinical possibilities of tone pip BAEPs were then examined as these components were proved to be the only stable responses present in sleep. It was found that threshold estimates to 5OOHz, lOOOHz and 4000Hz stimuli could be made to within 15dBSL in most cases. A final study looked more closely at methods of obtaining frequency specific information in sleeping subjects. Threshold estimates were made using established BAEP parameters and this was compared to a 40HZ procedure which recorded a series of BAEPs over a 100msec. time sweep. Results indicated that the 40mHz procedure was superior to existing techniques in estimating threshold to low frequency stimuli. This research has confirmed a role for the MLR and 40Hz response as alternative measures of hearing capability in waking subjects and proposes that the 40Hz technique is useful in measuring frequency specific thresholds although the responses recorded derive primarily from the brainstem.

SVRMHC prediction server for MHC-binding peptides

The binding between antigenic peptides (epitopes) and the MHC molecule is a key step in the cellular immune response. Accurate in silico prediction of epitope-MHC binding affinity can greatly expedite epitope screening by reducing costs and experimental effort. Recently, we demonstrated the appealing performance of SVRMHC, an SVR-based quantitative modeling method for peptide-MHC interactions, when applied to three mouse class I MHC molecules. Subsequently, we have greatly extended the construction of SVRMHC models and have established such models for more than 40 class I and class II MHC molecules. Here we present the SVRMHC web server for predicting peptide-MHC binding affinities using these models. Benchmarked percentile scores are provided for all predictions. The larger number of SVRMHC models available allowed for an updated evaluation of the performance of the SVRMHC method compared to other well- known linear modeling methods. SVRMHC is an accurate and easy-to-use prediction server for epitope-MHC binding with significant coverage of MHC molecules. We believe it will prove to be a valuable resource for T cell epitope researchers.

In silico prediction of peptide-MHC binding affinity using SVRMHC

The binding between peptide epitopes and major histocompatibility complex (MHC) proteins is a major event in the cellular immune response. Accurate prediction of the binding between short peptides and class I or class II MHC molecules is an important task in immunoinformatics. SVRMHC which is a novel method to model peptide-MHC binding affinities based on support rector machine regression (SVR) is described in this chapter. SVRMHC is among a small handful of quantitative modeling methods that make predictions about precise binding affinities between a peptide and an MHC molecule. As a kernel-based learning method, SVRMHC has rendered models with demonstrated appealing performance in the practice of modeling peptide-MHC binding.

Comparison of DSP-based nonlinear equalizers for intra-channel nonlinearity compensation in coherent optical OFDM

A novel versatile digital signal processing (DSP)-based equalizer using support vector machine regression (SVR) is proposed for 16-quadrature amplitude modulated (16-QAM) coherent optical orthogonal frequency-division multiplexing (CO-OFDM) and experimentally compared to traditional DSP-based deterministic fiber-induced nonlinearity equalizers (NLEs), namely the full-field digital back-propagation (DBP) and the inverse Volterra series transfer function-based NLE (V-NLE). For a 40 Gb/s 16-QAM CO-OFDM at 2000 km, SVR-NLE extends the optimum launched optical power (LOP) by 4 dB compared to V-NLE by means of reduction of fiber nonlinearity. In comparison to full-field DBP at a LOP of 6 dBm, SVR-NLE outperforms by ∼1 dB in Q-factor. In addition, SVR-NLE is the most computational efficient DSP-NLE.

Predicting delay reductions from freeway traffic diversion for incident management

Traffic incidents are a major source of traffic congestion on freeways. Freeway traffic diversion using pre-planned alternate routes has been used as a strategy to reduce traffic delays due to major traffic incidents. However, it is not always beneficial to divert traffic when an incident occurs. Route diversion may adversely impact traffic on the alternate routes and may not result in an overall benefit. This dissertation research attempts to apply Artificial Neural Network (ANN) and Support Vector Regression (SVR) techniques to predict the percent of delay reduction from route diversion to help determine whether traffic should be diverted under given conditions. The DYNASMART-P mesoscopic traffic simulation model was applied to generate simulated data that were used to develop the ANN and SVR models. A sample network that comes with the DYNASMART-P package was used as the base simulation network. A combination of different levels of incident duration, capacity lost, percent of drivers diverted, VMS (variable message sign) messaging duration, and network congestion was simulated to represent different incident scenarios. The resulting percent of delay reduction, average speed, and queue length from each scenario were extracted from the simulation output. The ANN and SVR models were then calibrated for percent of delay reduction as a function of all of the simulated input and output variables. The results show that both the calibrated ANN and SVR models, when applied to the same location used to generate the calibration data, were able to predict delay reduction with a relatively high accuracy in terms of mean square error (MSE) and regression correlation. It was also found that the performance of the ANN model was superior to that of the SVR model. Likewise, when the models were applied to a new location, only the ANN model could produce comparatively good delay reduction predictions under high network congestion level.

Predicting delay reductions from freeway traffic diversion for incident management

Traffic incidents are a major source of traffic congestion on freeways. Freeway traffic diversion using pre-planned alternate routes has been used as a strategy to reduce traffic delays due to major traffic incidents. However, it is not always beneficial to divert traffic when an incident occurs. Route diversion may adversely impact traffic on the alternate routes and may not result in an overall benefit. This dissertation research attempts to apply Artificial Neural Network (ANN) and Support Vector Regression (SVR) techniques to predict the percent of delay reduction from route diversion to help determine whether traffic should be diverted under given conditions. The DYNASMART-P mesoscopic traffic simulation model was applied to generate simulated data that were used to develop the ANN and SVR models. A sample network that comes with the DYNASMART-P package was used as the base simulation network. A combination of different levels of incident duration, capacity lost, percent of drivers diverted, VMS (variable message sign) messaging duration, and network congestion was simulated to represent different incident scenarios. The resulting percent of delay reduction, average speed, and queue length from each scenario were extracted from the simulation output. The ANN and SVR models were then calibrated for percent of delay reduction as a function of all of the simulated input and output variables. The results show that both the calibrated ANN and SVR models, when applied to the same location used to generate the calibration data, were able to predict delay reduction with a relatively high accuracy in terms of mean square error (MSE) and regression correlation. It was also found that the performance of the ANN model was superior to that of the SVR model. Likewise, when the models were applied to a new location, only the ANN model could produce comparatively good delay reduction predictions under high network congestion level.

Correlation between pre-treatment quasispecies complexity and treatment outcome in chronic HCV genotype 3a

Pre-treatment HCV quasispecies complexity and diversity may predict response to interferon based anti-viral therapy. The objective of this study was to retrospectively (1) examine temporal changes in quasispecies prior to the start of therapy and (2) investigate extensively quasispecies evolution in a group of 10 chronically infected patients with genotype 3a, treated with pegylated alpha 2a-Interferon and ribavirin. The degree of sequence heterogeneity within the hypervariable region 1 was assessed by analyzing 20-30 individual clones in serial serum samples. Genetic parameters, including amino acid Shannon entropy, Hamming distance and genetic distance were calculated for each sample. Treatment outcome was divided into (1) sustained virological responders (SVR) and (2) treatment failure (TF).Our results indicate, (1) quasispecies complexity and diversity are lower in the SVR group, (2) quasispecies vary temporally and (3) genetic heterogeneity at baseline can be used to predict treatment outcome. We discuss the results from the perspective of replicative homeostasis. We discuss the results from the perspective of replicative homeostasis.

Sequence and Structural Determinants of Specificity Differences between Paralogous Transcription Factors

Transcription factors (TFs) control the temporal and spatial expression of target genes by interacting with DNA in a sequence-specific manner. Recent advances in high throughput experiments that measure TF-DNA interactions in vitro and in vivo have facilitated the identification of DNA binding sites for thousands of TFs. However, it remains unclear how each individual TF achieves its specificity, especially in the case of paralogous TFs that recognize distinct target genomic sites despite sharing very similar DNA binding motifs. In my work, I used a combination of high throughput in vitro protein-DNA binding assays and machine-learning algorithms to characterize and model the binding specificity of 11 paralogous TFs from 4 distinct structural families. My work proves that even very closely related paralogous TFs, with indistinguishable DNA binding motifs, oftentimes exhibit differential binding specificity for their genomic target sites, especially for sites with moderate binding affinity. Importantly, the differences I identify in vitro and through computational modeling help explain, at least in part, the differential in vivo genomic targeting by paralogous TFs. Future work will focus on in vivo factors that might also be important for specificity differences between paralogous TFs, such as DNA methylation, interactions with protein cofactors, or the chromatin environment. In this larger context, my work emphasizes the importance of intrinsic DNA binding specificity in targeting of paralogous TFs to the genome.

Effekter av icke-farmakologiska metoder vid beteendemässiga och psykiska symtom hos personer som lever med Alzheimers sjukdom : En litteraturöversikt

Bakgrund: Alzheimers sjukdom (AD) är den vanligaste formen av demenssjukdomar och antalet människor som insjuknar i AD förväntas öka kraftigt med tiden. Dessutom kännetecknas personer med AD ofta av beteendemässiga och psykiska symtom (BPSD) som kan innefatta agitation, depression, vanföreställningar, oro, ångest, hallucinationer, sömnrubbningar, rastlöshet och apati. Dessa symtom kan orsaka lidande hos patienten och är svåra att hantera för både vårdgivaren och anhöriga, samt försvårar omvårdnadsarbetet. Syftet var att beskriva icke-farmakologiska metoder och effekter av dessa metoder vid omvårdnad av personer med Alzheimers sjukdom som har beteendemässiga och psykiska symtom. Metod: En litteraturöversikt bestående av 16 utvalda kvantitativa forskningsartiklar har genomförts. Artiklarna publicerades mellan år 2006-2016. Resultat. De studerade icke-farmakologiska metoderna var musikterapi, vissa typer av massage, reminiscence-terapi, vårdhundterapi och ljusterapi. Resultaten visade att icke-farmakologiska metoder kan ha en varierande effekt på BPSD. Litteraturöversikten visade att musikintervention var mest effektiv för att minska agitationsbeteende. Individualiserad musik i samband med speciella minnen minskade stress, fobier hos personer med svår demens. Intervention av handmassage, aromaterapi, taktil massage och terapeutisk beröring minskade aggression och agitationsbeteende. Vissa studier visade dock att fotmassageintervention och vårdhundterapi kunde öka verbal aggressivitet hos personer med demens, medan en annan studie visade att djurassisterade aktiviteter kunde minska nedstämdhet medan glädje och generell uppmärksamhet ökade. Effekten av ljusbehandling var förbättrad sömn, minskad depression, agitation och ätstörningar. Slutsats. Icke-farmakologiska metoder kan minska beteendemässiga och psykiska symtom hos personer med Alzheimers sjukdom, dock med varierande effekt. De varierande resultaten kan tolkas som att icke-farmakologiska metoder bör individanpassas och att det behövs vidare forskning inom området.

Sjuksköterskors erfarenheter och upplevelser av att vårda patienter med självskadebeteende : en kvalitativ intervjustudie

Bakgrund: Självskadebeteende är ett sedan länge förekommande fenomen som kan vara framträdande hos patienter med en oförmåga att reglera affekter. Det innebär ett lidande för patienterna och det bidrar till en känslomässig påverkan hos sjuksköterskorna. För att skapa en gynnsam omvårdnadsrelation behövs resurser, kunskap, kompetens och stöd för sjuksköterskorna i omvårdnaden. Syfte: Beskriva sjuksköterskans erfarenheter och upplevelser av att vårda patienter med självskadebeteende. Metod: Data samlades in från sex sjuksköterskor genom kvalitativa semi-strukturerade intervjuer med stöd av en intervjuguide. Materialet har analyserats med kvalitativ innehållsanalys. Resultat: Det framkom fyra kategorier "Att självskada", "Behov av kompetens", "Ge omvårdnad" och "Känslomässig påverkan". Sjuksköterskorna lyfte svårigheter i omvårdnaden, behovet av kompetens och den känslomässiga påverkan de drabbades av i mötet med patienter med självskadebeteende. Slutsats: Självskadebeteende skapar många olika känslor hos sjuksköterskorna, både positiva och negativa. Sjuksköterskorna upplevde att patienter med självskadebeteende var en svår, men intressant grupp att arbeta med. Tidsbrist, stress och upprepade självskadehandlingar var påfrestande och de känslor som uppkom hos sjuksköterskorna var inte alltid lätta för dem att hantera. Sjuksköterskorna poängterade vikten av att fånga upp patienter i tid men beskrev även svårigheterna i att kunna göra det. Sjuksköterskorna efterfrågade utökat stöd, kunskap och bättre resurser för att känna sig trygga i sin yrkesroll samt för att kunna erbjuda patienter med självskadebeteende en god och säker omvårdnad.

Cognitive Component Skills of Reading Comprehension in Developing Readers

Die Fähigkeit, geschriebene Texte zu verstehen, d.h. eine kohärente mentale Repräsentation von Textinhalten zu erstellen, ist eine notwendige Voraussetzung für eine erfolgreiche schulische und außerschulische Entwicklung. Es ist daher ein zentrales Anliegen des Bildungssystems Leseschwierigkeiten frühzeitig zu diagnostizieren und mithilfe zielgerichteter Interventionsprogramme zu fördern. Dies erfordert ein umfassendes Wissen über die kognitiven Teilprozesse, die dem Leseverstehen zugrunde liegen, ihre Zusammenhänge und ihre Entwicklung. Die vorliegende Dissertation soll zu einem umfassenden Verständnis über das Leseverstehen beitragen, indem sie eine Auswahl offener Fragestellungen experimentell untersucht. Studie 1 untersucht inwieweit phonologische Rekodier- und orthographische Dekodierfertigkeiten zum Satz- und Textverstehen beitragen und wie sich beide Fertigkeiten bei deutschen Grundschüler(inne)n von der 2. bis zur 4. Klasse entwickeln. Die Ergebnisse legen nahe, dass beide Fertigkeiten signifikante und eigenständige Beiträge zum Leseverstehen leisten und dass sich ihr relativer Beitrag über die Klassenstufen hinweg nicht verändert. Darüber hinaus zeigt sich, dass bereits deutsche Zweitklässler(innen) den Großteil geschriebener Wörter in altersgerechten Texten über orthographische Vergleichsprozesse erkennen. Nichtsdestotrotz nutzen deutsche Grundschulkinder offenbar kontinuierlich phonologische Informationen, um die visuelle Worterkennung zu optimieren. Studie 2 erweitert die bisherige empirische Forschung zu einem der bekanntesten Modelle des Leseverstehens—der Simple View of Reading (SVR, Gough & Tunmer, 1986). Die Studie überprüft die SVR (Reading comprehension = Decoding x Comprehension) mithilfe optimierter und methodisch stringenter Maße der Modellkonstituenten und überprüft ihre Generalisierbarkeit für deutsche Dritt- und Viertklässler(innen). Studie 2 zeigt, dass die SVR einer methodisch stringenten Überprüfung nicht standhält und nicht ohne Weiteres auf deutsche Dritt- und Viertklässler(innen) generalisiert werden kann. Es wurden nur schwache Belege für eine multiplikative Verknüpfung von Dekodier- (D) und Hörverstehensfertigkeiten (C) gefunden. Der Umstand, dass ein beachtlicher Teil der Varianz im Leseverstehen (R) nicht durch D und C aufgeklärt werden konnte, deutet darauf hin, dass das Modell nicht vollständig ist und ggf. durch weitere Komponenten ergänzt werden muss. Studie 3 untersucht die Verarbeitung positiv-kausaler und negativ-kausaler Kohärenzrelationen bei deutschen Erst- bis Viertklässler(inne)n und Erwachsenen im Lese- und Hörverstehen. In Übereinstimmung mit dem Cumulative Cognitive Complexity-Ansatz (Evers-Vermeul & Sanders, 2009; Spooren & Sanders, 2008) zeigt Studie 3, dass die Verarbeitung negativ-kausaler Kohärenzrelationen und Konnektoren kognitiv aufwändiger ist als die Verarbeitung positiv-kausaler Relationen. Darüber hinaus entwickelt sich das Verstehen beider Kohärenzrelationen noch über die Grundschulzeit hinweg und ist für negativ-kausale Relationen am Ende der vierten Klasse noch nicht abgeschlossen. Studie 4 zeigt und diskutiert die Nützlichkeit prozess-orientierter Lesetests wie ProDi- L (Richter et al., in press), die individuelle Unterschiede in den kognitiven Teilfertigkeiten des Leseverstehens selektiv erfassen. Hierzu wird exemplarisch die Konstruktvalidität des ProDi-L-Subtests ‚Syntaktische Integration’ nachgewiesen. Mittels explanatorischer Item- Repsonse-Modelle wird gezeigt, dass der Test Fertigkeiten syntaktischer Integration separat erfasst und Kinder mit defizitären syntaktischen Fertigkeiten identifizieren kann. Die berichteten Befunde tragen zu einem umfassenden Verständnis der kognitiven Teilfertigkeiten des Leseverstehens bei, das für eine optimale Gestaltung des Leseunterrichts, für das Erstellen von Lernmaterialien, Leseinstruktionen und Lehrbüchern unerlässlich ist. Darüber hinaus stellt es die Grundlage für eine sinnvolle Diagnose individueller Leseschwierigkeiten und für die Konzeption adaptiver und zielgerichteter Interventionsprogramme zur Förderung des Leseverstehens bei schwachen Leser(inne)n dar.

Historiebruk i skolan : Historielärares tankar och resonemang om historiebruk

Syftet med den här studien har varit att undersöka hur fem lärare uppfattar och ser på begreppet historiebruk samt hur de menar att de tillämpar historiebruk i en undervisning. Tidigare forskning visar att begreppet historiebruk definieras, tillämpas och uttrycks på en mängd olika sätt. Skolinspektionen anser att historieundervisningen inte ger elever möjligheten att få träna sig i förmågan att analysera och resonera om historiebruk. Lärare uttrycker också en osäkerhet i hur en undervisning om historiebruk ska se ut. Forskning visar också att elever har svårt att tänka ab-strakt, som att ta sig mellan olika tidsdimensioner, vilket krävs för att kunna genomföra en analys av historiebruk. Av ovan nämnda anledningar avsåg denna studie att undersöka vidare på lärarnas förståelse om be-greppet historiebruk och hur de ser på att tillämpa historiebruk i historieundervisningen. Denna stu-die har därför intervjuat fem aktiva historielärare och därefter analyserat deras svar utifrån aktuell litteratur och forskning. Det huvudsakliga resultatet är att det finns en osäkerhet i hur man skall förstå själva begreppet histo-riebruk. Av intervjuerna framkommer att lärarna ger olika slags förklaringar till vad det är. Man för-står det till exempel som en förlängning av källkritik, att det är att se spår av det förflutna samt att det är själva syftet med historieundervisningen. På frågan hur lärarna ser på hur man kan tillämpa historiebruk i en undervisning anser lärarna att analys av historiebruk är en svår kognitiv process för elever i årskurs 7-9. Dessutom menar de att det krävs mycket goda förkunskaper för att kunna genomföra en analys om historiebruk.

Association between the il28b rs12979860 polymorphism and therapy response in patients infected with genotype 1 of hepatitis c virus in Central Brazil

v. 45, n.2, p.152-160, abr/.jun. 2016.

Quasispecies dynamics and treatment outcome during early hepatitis C infection in a cohort of HIV-infected men

Hepatitis C virus (HCV) is emerging as one of the leading causes of morbidity and mortality in individuals infected with HIV and has overtaken AIDS-defining illnesses as a cause of death in HIV patient populations who have access to highly active antiretroviral therapy. For many years, the clonal analysis was the reference method for investigating viral diversity. In this thesis, a next generation sequencing (NGS) approach was developed using 454 pyrosequencing and Illumina-based technology. A sequencing pipeline was developed using two different NGS approaches, nested PCR, and metagenomics. The pipeline was used to study the viral populations in the sera of HCV-infected patients from a unique cohort of 160 HIV-positive patients with early HCV infection. These pipelines resulted in an improved understanding of HCV quasispecies dynamics, especially regarding studying response to treatment. Low viral diversity at baseline correlated with sustained virological response (SVR) while high viral diversity at baseline was associated with treatment failure. The emergence of new viral strains following treatment failure was most commonly associated with emerging dominance of pre-existing minority variants rather than re-infection. In the new era of direct-acting antivirals, next generation sequencing technologies are the most promising tool for identifying minority variants present in the HCV quasispecies populations at baseline. In this cohort, several mutations conferring resistance were detected in genotype 1a treatment-naïve patients. Further research into the impact of baseline HCV variants on SVR rates should be carried out in this population. A clearer understanding of the properties of viral quasispecies would enable clinicians to make improved treatment choices for their patients.

Does Epoetin Beta Still Have a Place in Peginterferon Alpha-2a Plus Ribavirin Treatment Strategies for Chronic Hepatitis C?

International audience