BadiRate: estimating family turnover rates by likelihood-based methods

Motivation: The comparative analysis of gene gain and loss rates is critical for understanding the role of natural selection and adaptation in shaping gene family sizes. Studying complete genome data from closely related species allows accurate estimation of gene family turnover rates. Current methods and software tools, however, are not well designed for dealing with certain kinds of functional elements, such as microRNAs or transcription factor binding sites. Results: Here, we describe BadiRate, a new software tool to estimate family turnover rates, as well as the number of elements in internal phylogenetic nodes, by likelihood-based methods and parsimony. It implements two stochastic population models, which provide the appropriate statistical framework for testing hypothesis, such as lineage-specific gene family expansions or contractions. We have assessed the accuracy of BadiRate by computer simulations, and have also illustrated its functionality by analyzing a representative empirical dataset.

A comparison of Bayesian and frequentist approaches to incorporating external information for the prediction of prostate cancer risk.

We present the most comprehensive comparison to date of the predictive benefit of genetics in addition to currently used clinical variables, using genotype data for 33 single-nucleotide polymorphisms (SNPs) in 1,547 Caucasian men from the placebo arm of the REduction by DUtasteride of prostate Cancer Events (REDUCE®) trial. Moreover, we conducted a detailed comparison of three techniques for incorporating genetics into clinical risk prediction. The first method was a standard logistic regression model, which included separate terms for the clinical covariates and for each of the genetic markers. This approach ignores a substantial amount of external information concerning effect sizes for these Genome Wide Association Study (GWAS)-replicated SNPs. The second and third methods investigated two possible approaches to incorporating meta-analysed external SNP effect estimates - one via a weighted PCa 'risk' score based solely on the meta analysis estimates, and the other incorporating both the current and prior data via informative priors in a Bayesian logistic regression model. All methods demonstrated a slight improvement in predictive performance upon incorporation of genetics. The two methods that incorporated external information showed the greatest receiver-operating-characteristic AUCs increase from 0.61 to 0.64. The value of our methods comparison is likely to lie in observations of performance similarities, rather than difference, between three approaches of very different resource requirements. The two methods that included external information performed best, but only marginally despite substantial differences in complexity.

Quantitative multi-parameter mapping of R1, PD(*), MT, and R2(*) at 3T: a multi-center validation.

Multi-center studies using magnetic resonance imaging facilitate studying small effect sizes, global population variance and rare diseases. The reliability and sensitivity of these multi-center studies crucially depend on the comparability of the data generated at different sites and time points. The level of inter-site comparability is still controversial for conventional anatomical T1-weighted MRI data. Quantitative multi-parameter mapping (MPM) was designed to provide MR parameter measures that are comparable across sites and time points, i.e., 1 mm high-resolution maps of the longitudinal relaxation rate (R1 = 1/T1), effective proton density (PD(*)), magnetization transfer saturation (MT) and effective transverse relaxation rate (R2(*) = 1/T2(*)). MPM was validated at 3T for use in multi-center studies by scanning five volunteers at three different sites. We determined the inter-site bias, inter-site and intra-site coefficient of variation (CoV) for typical morphometric measures [i.e., gray matter (GM) probability maps used in voxel-based morphometry] and the four quantitative parameters. The inter-site bias and CoV were smaller than 3.1 and 8%, respectively, except for the inter-site CoV of R2(*) (<20%). The GM probability maps based on the MT parameter maps had a 14% higher inter-site reproducibility than maps based on conventional T1-weighted images. The low inter-site bias and variance in the parameters and derived GM probability maps confirm the high comparability of the quantitative maps across sites and time points. The reliability, short acquisition time, high resolution and the detailed insights into the brain microstructure provided by MPM makes it an efficient tool for multi-center imaging studies.

A new early and automated MRI-based predictor of motor improvement after stroke.

OBJECTIVES: In this study, we investigated the structural plasticity of the contralesional motor network in ischemic stroke patients using diffusion magnetic resonance imaging (MRI) and explored a model that combines a MRI-based metric of contralesional network integrity and clinical data to predict functional outcome at 6 months after stroke. METHODS: MRI and clinical examinations were performed in 12 patients in the acute phase, at 1 and 6 months after stroke. Twelve age- and gender-matched controls underwent 2 MRIs 1 month apart. Structural remodeling after stroke was assessed using diffusion MRI with an automated measurement of generalized fractional anisotropy (GFA), which was calculated along connections between contralesional cortical motor areas. The predictive model of poststroke functional outcome was computed using a linear regression of acute GFA measures and the clinical assessment. RESULTS: GFA changes in the contralesional motor tracts were found in all patients and differed significantly from controls (0.001 ≤ p < 0.05). GFA changes in intrahemispheric and interhemispheric motor tracts correlated with age (p ≤ 0.01); those in intrahemispheric motor tracts correlated strongly with clinical scores and stroke sizes (p ≤ 0.001). GFA measured in the acute phase together with a routine motor score and age were a strong predictor of motor outcome at 6 months (r(2) = 0.96, p = 0.0002). CONCLUSION: These findings represent a proof of principle that contralesional diffusion MRI measures may provide reliable information for personalized rehabilitation planning after ischemic motor stroke. Neurology® 2012;79:39-46.

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.

Detecting, quantifying and adjusting for publication bias in meta-analyses: protocol of a systematic review on methods.

BACKGROUND: Health professionals and policymakers aspire to make healthcare decisions based on the entire relevant research evidence. This, however, can rarely be achieved because a considerable amount of research findings are not published, especially in case of 'negative' results - a phenomenon widely recognized as publication bias. Different methods of detecting, quantifying and adjusting for publication bias in meta-analyses have been described in the literature, such as graphical approaches and formal statistical tests to detect publication bias, and statistical approaches to modify effect sizes to adjust a pooled estimate when the presence of publication bias is suspected. An up-to-date systematic review of the existing methods is lacking. METHODS/DESIGN: The objectives of this systematic review are as follows:âeuro¢ To systematically review methodological articles which focus on non-publication of studies and to describe methods of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses.âeuro¢ To appraise strengths and weaknesses of methods, the resources they require, and the conditions under which the method could be used, based on findings of included studies.We will systematically search Web of Science, Medline, and the Cochrane Library for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses. A dedicated data extraction form is developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article. As this will be a qualitative systematic review, data reporting will involve a descriptive summary. DISCUSSION: Results are expected to be publicly available in mid 2013. This systematic review together with the results of other systematic reviews of the OPEN project (To Overcome Failure to Publish Negative Findings) will serve as a basis for the development of future policies and guidelines regarding the assessment and handling of publication bias in meta-analyses.

Computational analysis of the genetic and environmental contributions to disease-related human phenotypes: From predicting adverse lipid response of HIV patients receiving antiretroviral therapy to genome-wide association studies of cardiovascular and lipid related disorders

Genetic variants influence the risk to develop certain diseases or give rise to differences in drug response. Recent progresses in cost-effective, high-throughput genome-wide techniques, such as microarrays measuring Single Nucleotide Polymorphisms (SNPs), have facilitated genotyping of large clinical and population cohorts. Combining the massive genotypic data with measurements of phenotypic traits allows for the determination of genetic differences that explain, at least in part, the phenotypic variations within a population. So far, models combining the most significant variants can only explain a small fraction of the variance, indicating the limitations of current models. In particular, researchers have only begun to address the possibility of interactions between genotypes and the environment. Elucidating the contributions of such interactions is a difficult task because of the large number of genetic as well as possible environmental factors.In this thesis, I worked on several projects within this context. My first and main project was the identification of possible SNP-environment interactions, where the phenotypes were serum lipid levels of patients from the Swiss HIV Cohort Study (SHCS) treated with antiretroviral therapy. Here the genotypes consisted of a limited set of SNPs in candidate genes relevant for lipid transport and metabolism. The environmental variables were the specific combinations of drugs given to each patient over the treatment period. My work explored bioinformatic and statistical approaches to relate patients' lipid responses to these SNPs, drugs and, importantly, their interactions. The goal of this project was to improve our understanding and to explore the possibility of predicting dyslipidemia, a well-known adverse drug reaction of antiretroviral therapy. Specifically, I quantified how much of the variance in lipid profiles could be explained by the host genetic variants, the administered drugs and SNP-drug interactions and assessed the predictive power of these features on lipid responses. Using cross-validation stratified by patients, we could not validate our hypothesis that models that select a subset of SNP-drug interactions in a principled way have better predictive power than the control models using "random" subsets. Nevertheless, all models tested containing SNP and/or drug terms, exhibited significant predictive power (as compared to a random predictor) and explained a sizable proportion of variance, in the patient stratified cross-validation context. Importantly, the model containing stepwise selected SNP terms showed higher capacity to predict triglyceride levels than a model containing randomly selected SNPs. Dyslipidemia is a complex trait for which many factors remain to be discovered, thus missing from the data, and possibly explaining the limitations of our analysis. In particular, the interactions of drugs with SNPs selected from the set of candidate genes likely have small effect sizes which we were unable to detect in a sample of the present size (<800 patients).In the second part of my thesis, I performed genome-wide association studies within the Cohorte Lausannoise (CoLaus). I have been involved in several international projects to identify SNPs that are associated with various traits, such as serum calcium, body mass index, two-hour glucose levels, as well as metabolic syndrome and its components. These phenotypes are all related to major human health issues, such as cardiovascular disease. I applied statistical methods to detect new variants associated with these phenotypes, contributing to the identification of new genetic loci that may lead to new insights into the genetic basis of these traits. This kind of research will lead to a better understanding of the mechanisms underlying these pathologies, a better evaluation of disease risk, the identification of new therapeutic leads and may ultimately lead to the realization of "personalized" medicine.

Growth of Crassostrea gasar cultured in marine and estuary environments in Brazilian waters

The objective of this work was to evaluate the growth of the mangrove oyster Crassostrea gasar cultured in marine and estuarine environments. Oysters were cultured for 11 months in a longline system in two study sites - São Francisco do Sul and Florianópolis -, in the state of Santa Catarina, Southern Brazil. Water chlorophyll-α concentration, temperature, and salinity were measured weekly. The oysters were measured monthly (shell size and weight gain) to assess growth. At the end of the culture period, the average wet flesh weight, dry flesh weight, and shell weight were determined, as well as the distribution of oysters per size class. Six nonlinear models (logistic, exponential, Gompertz, Brody, Richards, and Von Bertalanffy) were adjusted to the oyster growth data set. Final mean shell sizes were higher in São Francisco do Sul than in Florianópolis. In addition, oysters cultured in São Francisco do Sul were more uniformly distributed in the four size classes than those cultured in Florianópolis. The highest average values of wet flesh weight and shell weight were observed in São Francisco do Sul, whereas dry flesh weight did not differ between the sites. The estuary environment is more promising for the cultivation of oysters.

Intracellular thiol-mediated modulation of epithelial sodium channel activity.

The epithelial sodium channel ENaC is physiologically important in the kidney for the regulation of the extracellular fluid volume, and in the lungs for the maintenance of the appropriate airway surface liquid volume that lines the pulmonary epithelium. Besides the regulation of ENaC by hormones, intracellular factors such as Na(+) ions, pH, or Ca(2+) are responsible for fast adaptive responses of ENaC activity to changes in the intracellular milieu. In this study, we show that ENaC is rapidly and reversibly inhibited by internal sulfhydryl-reactive molecules such as methanethiosulfonate derivatives of different sizes, the metal cations Cd(2+) and Zn(2+), or copper(II) phenanthroline, a mild oxidizing agent that promotes the formation of disulfide bonds. At the single channel level, these agents applied intracellularly induce the appearance of long channel closures, suggesting an effect on ENaC gating. The intracellular reducing agent dithiothreitol fully reverses the rundown of ENaC activity in inside-out patches. Our observations suggest that changes in intracellular redox potential modulate ENaC activity and may regulate ENaC-mediated Na(+) transport in epithelia. Finally, substitution experiments reveal that multiple cysteine residues in the amino and carboxyl termini of ENaC subunits are responsible for this thiol-mediated inhibition of ENaC.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.

Effect of neighborhood and plot size on experiments with multiple-harvest oleraceous crops

The objective of this work was to determine the efficiency of the Papadakis method on the quality evaluation of experiments with multiple-harvest oleraceous crops, and on the estimate of the covariate and the ideal plot size. Data from nine uniformity trials (five with bean pod, two with zucchini, and two with sweet pepper) and from one experiment with treatments (with sweet pepper) were used. Through the uniformity trials, the best way to calculate the covariate was defined and the optimal plot size was calculated. In the experiment with treatments, analyses of variance and covariance were performed, in which the covariate was calculated by the Papadakis method, and experimental precision was evaluated based on four statistics. The use of analysis of covariance with the covariate obtained by the Papadakis method increases the quality of experiments with multiple-harvest oleraceous crops and allows the use of smaller plot sizes. The best covariate is the one that considers a neighboring plot of each side of the reference plot.

Naudan lietelannan käsittelymenetelmien taloudellinen vertailu

Maataloudessa syntyvä lanta on arvokas lannoite ja maanparannusaine, jonka käsittelystä aiheutuu sekä kustannuksia että ympäristövaikutuksia. Muita haasteita ovat esimerkiksi lannan mikrobit, lannan levitykseen soveltuvan ajankohdan lyhyys, lannan ravinteiden sovittaminen kasvien tarpeisiin ja lannan ravinteiden määrä suhteessa levityskelpoisen peltoalan määrään. Tutkimuksen tavoitteena oli tunnistaa naudan lietelannan käsittelyketjuihin liittyvät kustannukset ja osoittaa eri käsittelyketjujen kustannusten eroavaisuudet. Tavoitteena oli myös tunnistaa ja osoittaa käsittelyketjujen laadulliset erot. Kustannukset selvitettiin kustannuslaskelmin ja laadulliset erot SWOT-menetelmällä. Tutkimuksen kohteeksi valittiin 6 tilakokoluokkaa ja käsittelyketjuiksi lietelanta-, kompostointi- ja mädätysketju. Tutkimuksessa alhaisimmat kustannukset olivat lietelantaketjulla, jonka kustannukset 25 – 250 naudan tilalla olivat 5 200 – 6 600 €/a ja yksikkökustannukset 1 – 9 €/m3. Mädätysketjun kustannukset vastaavissa tilakokoluokissa olivat noin 33 000 – 50 000 €/a ja yksikkökustannukset 8 – 55 €/m3. Kompostointiketjun kustannukset olivat 35 000 – 143 000 €/a ja yksikkökustannukset 24 – 58 €/m3. Lietelantaketjun edullisuus johtui vähäisistä laite- ja rakennusinvestoinneista ja pienistä työmääristä ja kompostointiketjun kalleus suurista tukiaine- ja investointikustannuksista. Käsittelyketjujen asettaminen paremmuusjärjestykseen oli hankalaa. Työn määrä oli pienin lietelantaketjussa ja toiseksi pienin suurilla tiloilla mädätysketjussa. Kompostointiketjulla itse levitykseen kuluva aika oli pienin. Ravinteiden osalta mädätysketju oli parhain ja kompostointiketju huonoin. Ympäristövaikutuksiltaan ja hajuhaitoiltaan kompostointi- ja mädätysketju olivat parhaimmat. Mikrobien osalta parhain oli kompostointiketju.

LM-vesiturbiinin tuotteistaminen

Tämän työn tarkoituksena on kehittää LM-vesiturbiini tuotantoon soveltuvaksi, käytöltään pitkäikäiseksi ja helposti huollettavaksi tuotesarjaksi. Työn ohjaavana runkona on käytetty VDI-Richtlinie 2221: 'Kehitystyön ja konstruoinnin yleinen kulku', mukaista järjestelmää. Lisäksi on käytetty valmistuksellista modulointia tuotteen osien suunnittelussa. Erityisesti on huomioitu tuotteen koko elinkaaren aikaiset kustannukset (LCC) ja sen vaatimukset mitoitukseen. LM-vesiturbiinistaon kehitetty kolmen erikokoisen laitteiston tuotesarja. Tuoteperheen yksittäisistä sylinteriryhmistä voidaan koota joustavasti erikokoisia ja -tehoisia energiantuotantoyksiköitä, jotka soveltuvat käyttöön hyvin pieniinkin virtauksiin ja putouskorkeuksiin. Piensarjatuotantoon hyvin soveltuvat materiaalit on valittu silmälläpitäen mahdollisimman edullista kokonaiskustannusta. Kiertomäntä laitteiston toiminnan kannalta tärkeimpänä ja siten vaativimpana osana on edellyttänyt laserhitsausta ja -leikkausta sekä koekappaleiden valmistusta, joiden perusteellalopulliseen rakenteeseen on päädytty. Mitoitus perustuu perinteisiin lujuuslaskentamenetelmiin, joiden avulla eri osien kestävyys käyttöolosuhteissa on pyrittysaamaan luotettavaksi vähintään 20 vuoden kestoiälle ja väsymiskestävyyteen käytön aikaisissa vaihtelevissa olosuhteissa. Kiertomäntä on ns. kevytrakenne koostuen ohutlevykennorakenteesta ja täytteenä olevasta kompound-materiaalista.

Sormijatketun rakennesahatavaran lujuuteen vaikuttavat tekijät puun jatkojalostuksessa

Diplomityö tehtiin Stora Enson Kiteen sahalla, tuotantokäytössä olevaa sormijatkoslinjaa tutkien. Tutkimuksen tavoitteena oli selvittää raaka-aineen keskikosteuden, kosteusgradientin, mitallistamishöyläyksen ja liitettävien aihioiden pituuden vaikutus jatketun tuotteen laatuun. Koekappaleita valmistettiin viisi höylättyä ja viisi sahapintaista luokkaa. Luokat valmistettiin eripituisista aihioista, puolen metrin jaolla. Koekappaleiden taivutuslujuus mitattiin nelipistetaivutuksella, standardin EN 408 mukaan. Taivutuskokeen jälkeen kappaleista mitattiin keskikosteus ja sahattiin koepalat kosteusgradientin mittaamiseksi. Koekappaleita valmistettiin yhteensä 37.8 m3. Tutkimuksissa selvisi, että kappaleiden keskikosteuden ja taivutuslujuuden välillä vallitsee heikko positiivinen riippuvuus. Kosteusgradientin ja taivutuslujuuden välillä riippuvuus on selkeämpi, kosteusgradientin kasvaessa myös taivutuslujuus lisääntyy. Tämä selittyy kappaleiden tiheyden vaihtelulla. Tiheämpiin kappaleisiin jää kuivauksessa suurempi kosteusgradientti. Aihioiden mitallistaminen pienentää taivutuslujuuden hajontaa ja vähentää raaka-aineen mittaheittojen aiheuttamia häiriöitä tuotannossa. Aihionpituus vaikuttaa murtumatyyppien jakaumiin ja aihioiden kierouteen. Sopivin aihionpituus on tässä tapauksessa 0.8-1.0 m. Puolet kappaleista murtui liitoksen ulkopuolelta, useimmiten oksan kohdalta. Paras tapa parantaa kappaleiden lujuutta on lujuuslajitella raaka-aine.

Primääri-sekundäärivuodon tunnistaminen aktiivisuusmittauksin Loviisan voimalaitoksella

Diplomityössä tutkittiin Loviisan voimalaitoksen primääri- ja sekundääripiirin aktiivisuusmittausten kykyä tunnistaa pienet primääri-sekundäärivuodot. Tarkasteltavat primääri-sekundäärivuotojen suuruudet valittiin laitoksen hätätilanne- ja häiriönselvitysohjeiden mukaisesti. Vuodon vaikutuksia arvioitiin erilaisilla primäärijäähdytteen ominaisaktiivisuuksilla. Ominaisaktiivisuudet primääripiirissä määritettiin nuklidikohtaisesti erilaisille polttoainevuototapauksille. Työssä huomioitiin myös transienteissa mahdollisesti esiintyvä primääripiirin aktiivisuustasoa nostava spiking-ilmiö. Vuodon tarkempaa tunnistamista varten työssä laskettiin tarkasteltaville mittareille kalibrointikertoimet. Primääri-sekundäärivuoto mallinnettiin APROS-simulointiohjelmalla laitoksen eri käyttötiloissa ja kahdella eri vuotokoolla. Varsinainen aktiivisuuslaskenta suoritettiin SEKUN-ohjelmalla. Työssä tätä aktiivisuus- ja päästölaskentaohjelmaa muokattiin ohjelmoimalla siihen tarkasteltavat aktiivisuusmittaukset sekä primääripiirin puhdistus ja ulospuhallus. Laskelmien tuloksena saatiin arviot kunkin tarkasteltavana olleen aktiivisuusmittauksen soveltuvuudesta primääri-sekundäärivuodon tunnistamiseen erilaisissa polttoainevuototapauksissa ja reaktorin eri tehotasoilla. Häiriönselvitysohje I3:n käyttöönottoa edellyttävät vuotokoot määritettiin aktiivisuusmittausten havaitseman perusteella. Erityisesti kuumavalmiustilassa tapauksissa, joissa reaktorisydämessä oletetaan olevan tiiveytensä menettäneitä polttoainesauvoja, spikingin vaikutus jäähdytteiden aktiivisuuspitoisuuksiin ja mittaustuloksiin oli merkittävä. Niiltä osin, kuin tulokset käsittelevät ohjeissa vuodon tunnistamiseen käytettyjä aktiivisuusrajoja, tulokset osoittivat aktiivisuusrajat oikeiksi. Kuumavalmiudessa aktiivisuusmittausten mittausalueet saattavat joissakin tapauksissa rajoittaa primääri-sekundäärivuodon tunnistamista.