Impact of phenotype definition on genome-wide association signals: empirical evaluation in human immunodeficiency virus type 1 infection.

Discussion on improving the power of genome-wide association studies to identify candidate variants and genes is generally centered on issues of maximizing sample size; less attention is given to the role of phenotype definition and ascertainment. The authors used genome-wide data from patients infected with human immunodeficiency virus type 1 (HIV-1) to assess whether differences in type of population (622 seroconverters vs. 636 seroprevalent subjects) or the number of measurements available for defining the phenotype resulted in differences in the effect sizes of associations between single nucleotide polymorphisms and the phenotype, HIV-1 viral load at set point. The effect estimate for the top 100 single nucleotide polymorphisms was 0.092 (95% confidence interval: 0.074, 0.110) log(10) viral load (log(10) copies of HIV-1 per mL of blood) greater in seroconverters than in seroprevalent subjects. The difference was even larger when the authors focused on chromosome 6 variants (0.153 log(10) viral load) or on variants that achieved genome-wide significance (0.232 log(10) viral load). The estimates of the genetic effects tended to be slightly larger when more viral load measurements were available, particularly among seroconverters and for variants that achieved genome-wide significance. Differences in phenotype definition and ascertainment may affect the estimated magnitude of genetic effects and should be considered in optimizing power for discovering new associations.

[Archives de la parole]. , [Les Vêpres d'Asnières] : [chanson] ; [J'ai fait une maîtresse, trois jours y a pas longtemps] : [chanson] / [Ferdinand Brunot], collecteur ; [Amélie Moutard, 71 ans, cultivatrice], chant

[Traditions. France. Berry]

Différences induites par la définition des périodes diurnes et nocturnes sur la pression artérielle et le dipping lors d'une mesure ambulatoire de la pression artérielle [Effects of nighttime and daytime interval definition on blood pressure and dipping in patients referred for ambulatory blood pressure measurement].

Ambulatory blood pressure monitoring (ABPM) has become indispensable for the diagnosis and control of hypertension. However, no consensus exists on how daytime and nighttime periods should be defined. OBJECTIVE: To compare daytime and nighttime blood pressure (BP) defined by an actigraph and by body position with BP resulting from arbitrary daytime and nighttime periods. PATIENTS AND METHOD: ABPM, sleeping periods and body position were recorded simultaneously using an actigraph (SenseWear Armband(®)) in patients referred for ABPM. BP results obtained with the actigraph (sleep and position) were compared to the results obtained with fixed daytime (7a.m.-10p.m.) and nighttime (10p.m.-7a.m.) periods. RESULTS: Data from 103 participants were available. More than half of them were taking antihypertensive drugs. Nocturnal BP was lower (systolic BP: 2.08±4.50mmHg; diastolic BP: 1.84±2.99mmHg, P<0.05) and dipping was more marked (systolic BP: 1.54±3.76%; diastolic BP: 2.27±3.48%, P<0.05) when nighttime was defined with the actigraph. Standing BP was higher (systolic BP 1.07±2.81mmHg; diastolic BP: 1.34±2.50mmHg) than daytime BP defined by a fixed period. CONCLUSION: Diurnal BP, nocturnal BP and dipping are influenced by the definition of daytime and nighttime periods. Studies evaluating the prognostic value of each method are needed to clarify which definition should be used.

New directions in Stochastic Multicriteria Acceptability Analysis

Decisions taken in modern organizations are often multi-dimensional, involving multiple decision makers and several criteria measured on different scales. Multiple Criteria Decision Making (MCDM) methods are designed to analyze and to give recommendations in this kind of situations. Among the numerous MCDM methods, two large families of methods are the multi-attribute utility theory based methods and the outranking methods. Traditionally both method families require exact values for technical parameters and criteria measurements, as well as for preferences expressed as weights. Often it is hard, if not impossible, to obtain exact values. Stochastic Multicriteria Acceptability Analysis (SMAA) is a family of methods designed to help in this type of situations where exact values are not available. Different variants of SMAA allow handling all types of MCDM problems. They support defining the model through uncertain, imprecise, or completely missing values. The methods are based on simulation that is applied to obtain descriptive indices characterizing the problem. In this thesis we present new advances in the SMAA methodology. We present and analyze algorithms for the SMAA-2 method and its extension to handle ordinal preferences. We then present an application of SMAA-2 to an area where MCDM models have not been applied before: planning elevator groups for high-rise buildings. Following this, we introduce two new methods to the family: SMAA-TRI that extends ELECTRE TRI for sorting problems with uncertain parameter values, and SMAA-III that extends ELECTRE III in a similar way. An efficient software implementing these two methods has been developed in conjunction with this work, and is briefly presented in this thesis. The thesis is closed with a comprehensive survey of SMAA methodology including a definition of a unified framework.

Wigner higher-order spectra: definition, properties, computation and application to transient signal analysis

The Wigner higher order moment spectra (WHOS)are defined as extensions of the Wigner-Ville distribution (WD)to higher order moment spectra domains. A general class oftime-frequency higher order moment spectra is also defined interms of arbitrary higher order moments of the signal as generalizations of the Cohen’s general class of time-frequency representations. The properties of the general class of time-frequency higher order moment spectra can be related to theproperties of WHOS which are, in fact, extensions of the properties of the WD. Discrete time and frequency Wigner higherorder moment spectra (DTF-WHOS) distributions are introduced for signal processing applications and are shown to beimplemented with two FFT-based algorithms. One applicationis presented where the Wigner bispectrum (WB), which is aWHOS in the third-order moment domain, is utilized for thedetection of transient signals embedded in noise. The WB iscompared with the WD in terms of simulation examples andanalysis of real sonar data. It is shown that better detectionschemes can be derived, in low signal-to-noise ratio, when theWB is applied.

KPI definition for measuring customer extranet benefits for a forest company

Tutkimuksen tavoitteena oli määrittää hyötyjä, joita Stora Enso on saavuttanut ottamalla käyttöön extranet-järjestelmän, jonka avulla asiakkaat voivat seurata toimitusketjuaan. Tässä tutkimuksessa keskityttiin taloudellisten hyötyjen määrittämiseen ja aineettomien hyötyjen tutkiminen rajattiintyön ulkopuolelle. Samalla tuli kehittää mittarit itsepalveluasteiden laskemiseksi tietyille toiminnoille, joita asiakkaat voivat hyödyntää järjestelmässä. Myös toiminnot, joita järjestelmässä pääasiassa käytetään, tuli määrittää kvantitatiivisen tutkimuksen avulla. Myyntihenkilöstön haastattelut toimivat apuna laskettaessa taloudellisia hyötyjä. Teoriaosuudessa käsitellään yleisesti sähköisiä palveluita erityisesti yritysten välistä kaupankäyntiä koskevalla alueella. Myös toimitusketjua ja tunnusluku mittareiden rakentamista on esitelty yleisellä tasolla teoriaosassa. Työn keskeisimmät tulokset ovat itsepalveluasteiden mittarit, niiden avulla lasketut itsepalveluasteet sekä taloudelliset hyödyt, joita yrityson saavuttanut järjestelmän käyttöönoton jälkeen.

Comparing potentially avoidable hospitalization rates related to ambulatory care sensitive conditions in Switzerland: the need to refine the definition of health conditions and to adjust for population health status.

BACKGROUND: Regional rates of hospitalization for ambulatory care sensitive conditions (ACSC) are used to compare the availability and quality of ambulatory care but the risk adjustment for population health status is often minimal. The objectives of the study was to examine the impact of more extensive risk adjustment on regional comparisons and to investigate the relationship between various area-level factors and the properly adjusted rates. METHODS: Our study is an observational study based on routine data of 2 million anonymous insured in 26 Swiss cantons followed over one or two years. A binomial negative regression was modeled with increasingly detailed information on health status (age and gender only, inpatient diagnoses, outpatient conditions inferred from dispensed drugs and frequency of physician visits). Hospitalizations for ACSC were identified from principal diagnoses detecting 19 conditions, with an updated list of ICD-10 diagnostic codes. Co-morbidities and surgical procedures were used as exclusion criteria to improve the specificity of the detection of potentially avoidable hospitalizations. The impact of the adjustment approaches was measured by changes in the standardized ratios calculated with and without other data besides age and gender. RESULTS: 25% of cases identified by inpatient main diagnoses were removed by applying exclusion criteria. Cantonal ACSC hospitalizations rates varied from to 1.4 to 8.9 per 1,000 insured, per year. Morbidity inferred from diagnoses and drugs dramatically increased the predictive performance, the greatest effect found for conditions linked to an ACSC. More visits were associated with fewer PAH although very high users were at greater risk and subjects who had not consulted at negligible risk. By maximizing health status adjustment, two thirds of the cantons changed their adjusted ratio by more than 10 percent. Cantonal variations remained substantial but unexplained by supply or demand. CONCLUSION: Additional adjustment for health status is required when using ACSC to monitor ambulatory care. Drug-inferred morbidities are a promising approach.

Definition of key variables for the induction of optimal NY-ESO-1-specific T cells in HLA transgene mice.

An attractive treatment of cancer consists in inducing tumor-eradicating CD8(+) CTL specific for tumor-associated Ags, such as NY-ESO-1 (ESO), a strongly immunogenic cancer germ line gene-encoded tumor-associated Ag, widely expressed on diverse tumors. To establish optimal priming of ESO-specific CTL and to define critical vaccine variables and mechanisms, we used HLA-A2/DR1 H-2(-/-) transgenic mice and sequential immunization with immunodominant DR1- and A2-restricted ESO peptides. Immunization of mice first with the DR1-restricted ESO(123-137) peptide and subsequently with mature dendritic cells (DCs) presenting this and the A2-restriced ESO(157-165) epitope generated abundant, circulating, high-avidity primary and memory CD8(+) T cells that efficiently killed A2/ESO(157-165)(+) tumor cells. This prime boost regimen was superior to other vaccine regimes and required strong Th1 cell responses, copresentation of MHC class I and MHC class II peptides by the same DC, and resulted in upregulation of sphingosine 1-phosphate receptor 1, and thus egress of freshly primed CD8(+) T cells from the draining lymph nodes into circulation. This well-defined system allowed detailed mechanistic analysis, which revealed that 1) the Th1 cytokines IFN-gamma and IL-2 played key roles in CTL priming, namely by upregulating on naive CD8(+) T cells the chemokine receptor CCR5; 2) the inflammatory chemokines CCL4 (MIP-1beta) and CCL3 (MIP-1alpha) chemoattracted primed CD4(+) T cells to mature DCs and activated, naive CD8(+) T cells to DC-CD4 conjugates, respectively; and 3) blockade of these chemokines or their common receptor CCR5 ablated priming of CD8(+) T cells and upregulation of sphingosine 1-phosphate receptor 1. These findings provide new opportunities for improving T cell cancer vaccines.

Definition of linear color models in the RGB vector color space to detect red peaches in orchard images taken under natural illumination

This work proposes the detection of red peaches in orchard images based on the definition of different linear color models in the RGB vector color space. The classification and segmentation of the pixels of the image is then performed by comparing the color distance from each pixel to the different previously defined linear color models. The methodology proposed has been tested with images obtained in a real orchard under natural light. The peach variety in the orchard was the paraguayo (Prunus persica var. platycarpa) peach with red skin. The segmentation results showed that the area of the red peaches in the images was detected with an average error of 11.6%; 19.7% in the case of bright illumination; 8.2% in the case of low illumination; 8.6% for occlusion up to 33%; 12.2% in the case of occlusion between 34 and 66%; and 23% for occlusion above 66%. Finally, a methodology was proposed to estimate the diameter of the fruits based on an ellipsoidal fitting. A first diameter was obtained by using all the contour pixels and a second diameter was obtained by rejecting some pixels of the contour. This approach enables a rough estimate of the fruit occlusion percentage range by comparing the two diameter estimates.

Hiomon AI-järjestelmän toimivuuden arviointi

Työn tavoitteena oli uudentyyppisen hiontaprosessin ohjausjärjestelmän kehittäminen ja testaaminen UPM-Kymmene Kaukaan hiomossa. Uuden ohjausjärjestelmän perusajatuksena oli pitää yksittäistä hiomakiveä jatkuvasti optimaalisessa toimintapisteessä, ja hiomon kaikilla koneilla pyrittiin samaan kivenalusmassan laatuun. Uutta ohjaustapaa kutsuttiin Optimum operating point -strategiaksi (OOPS). Hiomakiven pitäminen optimaalisessa toimintapisteessä tapahtui pääosin vesiteräyskäsittelyllä, jonka intensiteettiä ohjasi asiantuntijajärjestelmä (AI-järjestelmä). Lisäksi testattiin ohjelmoidun anturan nopeussäädön vaikutusta hiomakoneen resurssien käyttöön. AI-järjestelmä päätteli vesiteräyskäsittelyn tarpeellisuuden CSF-mallin ja hiomakoneen resurssien perusteella. Seurannasta saatujen tulosten perusteella AI-järjestelmän käyttöönotto vesiteräyskäsittelyssä paransi tuotannon ja massan laadun tasaisuutta. Hiomakoneiden resurssien havaittiin pienenevän puunsyöttölinjan mukaisesti. Paksummat pöllit kerääntyvät linjan päähän, jolloin varsinkin hydrauliikkapaineiden tarve lisääntyy linjan päässä olevilla hiomakoneilla. Hiomakoneen resurssit saatiin paremmin käyttöön kuormittamalla konetta ohjelmoidulla anturan nopeussäädöllä (ONS) kuin vakioidulla anturan nopeussäädöllä (VNS). Kuitenkin hydraulipaineresurssien puutteellisuus rajoitti koeajon aikana ONS:n toimintaa. Resursseja ei optimoitu koeajon aikana, koska kiven pinnan haluttiin pysyvän mahdollisimman stabiilina. Kivelle ei suoritettu mekaanista käsittelyä, vaikka kivenpinnan massan kuljetuskapasiteetin havaittiin olevan huono. AI-järjestelmä otettiin ohjaamaan vesiteräyskäsittelyä vasta ONS - VNS -koeajon jälkeen. Mekaanisen rullateräyksen jälkeen massan ominaisuudet muuttuivat, koska kiven pinnan terävät särmät katkoivat kuituja alentaen massan sitoutumiskykyä. Heti rullakäsittelyn jälkeen mitattu CSF saattoi jopa alentua huomattavasti, mutta AI-järjestelmän laskema CSF nousi selvästi indikoiden energian ominaiskulutuksen (EOK) laskua. Muutaman päivän hionnan jälkeen mitattu ja laskettu CSF saavuttivat saman tason.

Product Definition Process for Mobile Radio System Product

Työn tarkoituksena oli tutkia tuotteen määrittelyyn liittyvää kirjallisuutta ja perehtyä tuotteen määrittelytyön nykytilaan kohdeyrityksessä. Näihin molempiin perustuen muodostetaan prosessimalli tuotteen määrittelytyölle kohdeyrityksessä. Työssä käsitellään prosessijohtamisen pääperiaatteet sekä tuotteen määrittelyä koskevaa kirjallisuutta ja tutkimuksia. Koska kysessä oleva tuote on suurelta osalta ohjelmistotuote, ohjelmistojen suunnittelua, erityisesti ohjelmistovaatimusten hallintaa ja ohjelmistojen määrittelyä, on myös tarkasteltu työssä. Tuotteen määrittelyn haasteita on käsitelty yksityiskohtaisemmin, esimerkiksi dokumentointia, prosessin kulkua, vaatimusten epävakaisuutta sekä muutoksia. Kohdeyritys ja sen ongelmakohdat esitellään ja luodaan prosessimalli. Tämä malli esittelee seuraavat prosessit: raakavaatimusten hallinta -prosessin, roadmapping -prosessin, esisuunnittelu- ja spesifikaatioprosessin ja julkaisun suunnittelu -prosessin. Kaikki nämä ovat vaiheita ennen varsinaisen tuotekehitysprojektin aloittamista. Työssä esitellään myös kolmetasoinen dokumentaatiomalli.