Identification of Laboratory Techniques to Optimize Superpave HMA Surface Friction Characteristics, TR-450, 2010

Wet pavement friction is known to be one of the most important roadway safety parameters. In this research, frictional properties of flexible (asphalt) pavements were investigated. As a part of this study, a laboratory device to polish asphalt specimens was refined and a procedure to evaluate mixture frictional properties was proposed. Following this procedure, 46 different Superpave mixtures, one stone matrix asphalt (SMA) mixture and one porous friction course (PFC) mixture were tested. In addition, 23 different asphalt and two concrete field sections were also tested for friction and noise. The results of both field and laboratory measurements were used to develop an International Friction Index (IFI)-based protocol for measurement of the frictional characteristics of asphalt pavements for laboratory friction measurements. Based on the results of the study, it appears the content of high friction aggregate should be 20% or more of the total aggregate blend when used with other, polish susceptible coarse aggregates; the frictional properties increased substantially as the friction aggregate content increased above 20%. Both steel slag and quartzite were found to improve the frictional properties of the blend, though steel slag had a lower polishing rate. In general, mixes containing soft limestone demonstrated lower friction values than comparable mixes with hard limestone or dolomite. Larger nominal maximum aggregate size mixes had better overall frictional performance than smaller sized mixes. In addition, mixes with higher fineness moduli generally had higher macrotexture and friction.

Quantitative Mapping of Waterways Characteristics at Bridge Sites, TR-569, 2008

Iowa state, county, and city engineering offices expend considerable effort monitoring the state’s approximately 25,000 bridges, most of which span small waterways. In fact, the need for monitoring is actually greater for bridges over small waterways because scour processes are exacerbated by the close proximity of abutments, piers, channel banks, approach embankments, and other local obstructions. The bridges are customarily inspected biennially by the county’s road department bridge inspectors. It is extremely time consuming and difficult to obtain consistent, reliable, and timely information on bridge-waterway conditions for so many bridges. Moreover, the current approaches to gather survey information is not uniform, complete, and quantitative. The methodology and associated software (DIGIMAP) developed through the present project enable a non-intrusive means to conduct fast, efficient, and accurate inspection of the waterways in the vicinity of the bridges and culverts using one technique. The technique combines algorithms image of registration and velocimetry using images acquired with conventional devices at the inspection site. The comparison of the current bridge inspection and monitoring methods with the DIGIMAP methodology enables to conclude that the new procedure assembles quantitative information on the waterway hydrodynamic and morphologic features with considerable reduced effort, time, and cost. It also improves the safety of the bridge and culvert inspections conducted during normal and extreme hydrologic events. The data and information are recorded in a digital format, enabling immediate and convenient tracking of the waterway changes over short or long time intervals.

Spectral induced polarization: Laboratory measurements on sandy quartz samples of varied pore characteristics

Understanding the influence of pore space characteristics on the hydraulic conductivity and spectral induced polarization (SIP) response is critical for establishing relationships between the electrical and hydrological properties of surficial sedimentary deposits. Here, we present the results of laboratory SIP measurements on saturated quartz samples with granulometric characteristics ranging from fine sand to fine gravel. We alter the pore characteristics using three principal methods: (i) variation of the grain sizes, (ii) changing the degree of compaction, and (iii) changing the level of sorting. We then examine how these changes affect both the SIP response and the hydraulic conductivity. In general, the results indicate a clear connection between the applied changes in pore characteristics and the SIP response. In particular, we observe a systematic correlation between the hydraulic conductivity and the relaxation time of the Cole-Cole model describing the observed SIP effect for the whole range of considered grain sizes.

Insights into the Design and Characteristics of the Sedimentation Process at Multi-Barrel Culverts in Iowa, TR-596, 2010

The present study is an integral part of a broader study focused on the design and implementation of self-cleaning culverts, i.e., configurations that prevent the formation of sediment deposits after culvert construction or cleaning. Sediment deposition at culverts is influenced by many factors, including the size and characteristics of material of which the channel is composed, the hydraulic characteristics generated under different hydrology events, the culvert geometry design, channel transition design, and the vegetation around the channel. The multitude of combinations produced by this set of variables makes the investigation of practical situations a complex undertaking. In addition to the considerations above, the field and analytical observations have revealed flow complexities affecting the flow and sediment transport through culverts that further increase the dimensions of the investigation. The flow complexities investigated in this study entail: flow non-uniformity in the areas of transition to and from the culvert, flow unsteadiness due to the flood wave propagation through the channel, and the asynchronous correlation between the flow and sediment hydrographs resulting from storm events. To date, the literature contains no systematic studies on sediment transport through multi-box culverts or investigations on the adverse effects of sediment deposition at culverts. Moreover, there is limited knowledge about the non-uniform, unsteady sediment transport in channels of variable geometry. Furthermore, there are few readily useable (inexpensive and practical) numerical models that can reliably simulate flow and sediment transport in such complex situations. Given the current state of knowledge, the main goal of the present study is to investigate the above flow complexities in order to provide the needed insights for a series of ongoing culvert studies. The research was phased so that field observations were conducted first to understand the culvert behavior in Iowa landscape. Modeling through complementary hydraulic model and numerical experiments was subsequently carried out to gain the practical knowledge for the development of the self-cleaning culvert designs.

Trends over time of virological and immunological characteristics in the Swiss HIV Cohort Study.

BACKGROUND: The long-term outcome of antiretroviral therapy (ART) is not assessed in controlled trials. We aimed to analyse trends in the population effectiveness of ART in the Swiss HIV Cohort Study over the last decade. METHODS: We analysed the odds of stably suppressed viral load (ssVL: three consecutive values <50 HIV-1 RNA copies/mL) and of CD4 cell count exceeding 500 cells/μL for each year between 2000 and 2008 in three scenarios: an open cohort; a closed cohort ignoring the influx of new participants after 2000; and a worst-case closed cohort retaining lost or dead patients as virological failures in subsequent years. We used generalized estimating equations with sex, age, risk, non-White ethnicity and era of starting combination ART (cART) as fixed co-factors. Time-updated co-factors included type of ART regimen, number of new drugs and adherence to therapy. RESULTS: The open cohort included 9802 individuals (median age 38 years; 31% female). From 2000 to 2008, the proportion of participants with ssVL increased from 37 to 64% [adjusted odds ratio (OR) per year 1.16 (95% CI 1.15-1.17)] and the proportion with CD4 count >500 cells/μL increased from 40 to >50% [OR 1.07 (95% CI 1.06-1.07)]. Similar trends were seen in the two closed cohorts. Adjustment did not substantially affect time trends. CONCLUSIONS: There was no relevant dilution effect through new participants entering the open clinical cohort, and the increase in virological/immunological success over time was not an artefact of the study design of open cohorts. This can partly be explained by new treatment options and other improvements in medical care.

Assessment of diesel exhaust particulate exposure and surface characteristics in association with levels of oxidative stress biomarkers

Exposure to PM10 and PM2.5 (particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm, respectively) is associated with a range of adverse health effects, including cancer, pulmonary and cardiovascular diseases. Surface characteristics (chemical reactivity, surface area) are considered of prime importance to understand the mechanisms which lead to harmful effects. A hypothetical mechanism to explain these adverse effects is the ability of components (organics, metal ions) adsorbed on these particles to generate Reactive Oxygen Species (ROS), and thereby to cause oxidative stress in biological systems (Donaldson et al., 2003). ROS can attack almost any cellular structure, like DNA or cellular membrane, leading to the formation of a wide variety of degradation products which can be used as a biomarker of oxidative stress. The aim of the present research project is to test whether there is a correlation between the exposure to Diesel Exhaust Particulate (DEP) and the oxidative stress status. For that purpose, a survey has been conducted in real occupational situations where workers were exposed to DEP (bus depots). Different exposure variables have been considered: - particulate number, size distribution and surface area (SMPS); - particulate mass - PM2.5 and PM4 (gravimetry); - elemental and organic carbon (coulometry); - total adsorbed heavy metals - iron, copper, manganese (atomic adsorption); - surface functional groups present on aerosols (Knudsen flow reactor). Several biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and several aldehydes) have been determined either in urine or serum of volunteers. Results obtained during the sampling campaign in several bus depots indicated that the occupational exposure to particulates in these places was rather low (40-50 μg/m3 for PM4). Bimodal size distributions were generally observed (5 μm and <1 μm). Surface characteristics of PM4 varied strongly, depending on the bus depot. They were usually characterized by high carbonyl and low acidic sites content. Among the different biomarkers which have been analyzed within the framework of this study, mean urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly (p<0.05) during two consecutive days of exposure for non-smoker workers. On the other hand, no statistically significant differences were observed for serum levels of hexanal, nonanal and 4- hydroxy-nonenal (p>0.05). Biomarkers levels will be compared to exposure variables to gain a better understanding of the relation between the particulate characteristics and the formation of ROS by-products. This project is financed by the Swiss State Secretariat for Education and Research. It is conducted within the framework of the COST Action 633 "Particulate Matter - Properties Related to Health Effects".

Temporal variation in glucocorticoid levels during the resting phase is associated in opposite way with maternal and paternal melanic coloration.

Sex-dependent selection can help maintain sexual dimorphism. When the magnitude of selection exerted on a heritable sex trait differs between the sexes, it may prevent each sex to reach its phenotypic optimum. As a consequence, the benefit of expressing a sex trait to a given value may differ between males and females favouring sex-specific adaptations associated with different values of a sex trait. The level of metabolites regulated by genes that are under sex-dependent selection may therefore covary with the degree of ornamentation differently in the two sexes. We investigated this prediction in the barn owl, a species in which females display on average larger black spots on the plumage than males, a heritable ornament. This melanin-based colour trait is strongly selected in females and weakly counter-selected in males indicating sex-dependent selection. In nestling barn owls, we found that daily variation in baseline corticosterone levels, a key hormone that mediates life history trade-offs, covaries with spot diameter displayed by their biological parents. When their mother displayed larger spots, nestlings had lower corticosterone levels in the morning and higher levels in the evening, whereas the opposite pattern was found with the size of paternal spots. Our study suggests a link between daily regulation of glucocorticoids and sex-dependent selection exerted on sexually dimorphic melanin-based ornaments.

Red clover grown in a mixture with grasses : yield, persistence and dynamics of quality characteristics

Selostus: Puna-apilan pysyvyys apila-heinänurmessa sekä seosnurmen satoisuus ja laadun muutokset erilaisissa kasvuoloissa

Clinical and molecular characteristics of HNSCC patients with brain metastases: a retrospective study.

Among the metastasis patterns of head and neck squamous cell carcinoma (HNSCC), intracranial spread is a rare but dreaded event. To date only very few cases have been reported and clinical and molecular data are sparse. We screened our archives for HNSCC patients from 1992 to 2005 who were diagnosed with brain metastases (BM). For retrospective analysis, all clinico-pathological data including disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) were compiled. Additionally, we assessed the mutational status of the TP53 gene and the prevalence of HPV serotypes by PCR and Sanger sequencing. Immunohistochemistry was applied to detect p16INK4A expression levels as surrogate marker for HPV infection. The prevalence rate of BM in our cohort comprising 193 patients with advanced HNSCC was 5.7 %. Of 11 patients with BM, 3 were female and 9 were male. Seven of the primary tumors were of oropharyngeal origin (OPSCC). LPFS of the cohort was 11.8 months, DFS was 12.1 months and OS was 36.0 months. After the diagnosis of BM, survival was 10.5 months. Five tumors showed a mutation in the TP53 gene, while five of the seven OPSCC tumors had a positive HPV status displaying infection with serotype 16 in all cases. Compared with patients who harbored TP53wt/HPV-positive tumors, patients with TP53 mutations showed a poor prognosis. Compared with the whole cohort, the interval between diagnosis of the primary and the detection of BM was prolonged in the HPV-infected OPSCC subgroup (26.4 vs. 45.6 months). The prognosis of HNSCC patients with BM is poor. In our cohort, most tumors were OPSCC with the majority being HPV positive. Our study points toward a putatively unusual metastatic behavior of HPV-positive OPSCC.

Regulation of sodium transport in the cortical collecting duct : physiological role of GILZ in vitro and in vivo : characterisation of Na+ transport in the mCCDcl1 cell line

SUMMARY Regulation of sodium excretion by the kidney is a key mechanism in the long term regulation of blood pressure, and when altered it constitutes a risk factor for the appearance of arterial hypertension. Aldosterone, which secretion depends upon salt intake in the diet, is a steroid hormone that regulates sodium reabsorption in the distal part of the nephron (functional unit of the kidney) by modulating gene transcription. It has been shown that it can act synergistically with the peptidic hormone insulin through the interaction of their signalisation pathways. Our work consisted of two distinct parts: 1) the in vitro and in vivo characterisation of Glucocorticoid-Induced Leucine Zipper (GILZ) (an aldosterone-induced gene) mechanism of action; 2) the in vitro characterisation of insulin mechanism of action and its interaction with aldosterone. GILZ mRNA, coded by the TSC22D3 gene, is strongly induced by aldosterone in the cell line of principal cells of the cortical collecting duct (CCD) mpkCCDc14, suggesting that GILZ is a mediator of aldosterone response. Co-expression of GILZ and the amiloride-sensitive epithelial sodium channel ENaC in vitro in the Xenopus oocyte expression system showed that GILZ has no direct effect on the ENaC-mediated Na+ current in basal conditions. To define the role of GILZ in the kidney and in other organs (colon, heart, skin, etc.), a conditional knock-out mouse is being produced and will allow the in vivo study of its role. Previous data showed that insulin induced a transepithelial sodium transport at supraphysiological concentrations. Insulin and the insulin-like growth factor 1 (IGF-1) are able to bind to each other receptor with an affinity 50 to 100 times lower than to their cognate receptor. Our starting hypothesis was that the insulin effect observed at these supraphysiological concentrations is actually mediated by the IGF receptor type 1 (IGF-1R). In a new cell line that presents all the characteristics of the principal cells of the CCD (mCCDc11) we have shown that both insulin and IGF-1 induce a physiologically significant increase of Na+ transport through the activation of IGF-1R. Aldosterone and insulin/IGF-1 have an additive effect on Na+ transport, through the activation of the PI3-kinase (PI3-K) pathway and the phosphorylation of the serum- and glucocorticoid-induced kinase 1 (Sgk1) by the IGF-1R, and the induction of Sgk1 expression by aldosterone. Thus, Sgk1 integrates IGF-1/insulin and aldosterone effects. We suggest that IGF-1 is physiologically relevant in the modulation of sodium balance, while insulin can only regulate Na+ transport at supraphysiological conditions. Both hormones would bind to the IGF-1R and induce Na+ transport by activating the PI3-K PDK1/2 - Sgk1 pathway. We have shown for the first time that Sgk1 is expressed and phosphorylated in principal cells of the CCD in basal conditions, although the mechanism that maintains Sgk1 phosphorylation is not known. This new role for IGF-1 suggests that it could be a salt susceptibility gene. In effect, IGF-1 stimulates Na+ and water transport in the kidney in vivo. Moreover, 35 % of the acromegalic patients (overproduction of growth hormone and IGF-1) are hypertensives (higher proportion than in normal population), and genetic analysis suggest a link between the IGF-1 gene locus and blood pressure. RÉSUMÉ La régulation de l'excrétion rénale de sodium (Na+) joue un rôle principal dans le contrôle à long terme de la pression sanguine, et ses altérations constituent un facteur de risque de l'apparition d'une hypertension artérielle. L'aldosterone, dont la sécrétion dépend de l'apport en sel dans la diète, est une hormone stéroïdienne qui régule la réabsorption de Na+ dans la partie distale du nephron (unité fonctionnelle du rein) en contrôlant la transcription de gènes. Elle peut agir de façon synergistique avec l'hormone peptidique insuline, probablement via l'interaction de leurs voies de signalisation cellulaire. Le but de notre travail comportait deux volets: 1) caractériser in vitro et in vivo le mécanisme d'action du Glucocorticoid Induced Leucine Zipper (GILZ) (un gène induit par l'aldosterone); 2) caractériser in vitro le mécanisme d'action de l'insuline et son interaction avec l'aldosterone. L'ARNm de GILZ, codé par le gène TSC22D3, est induit par l'aldosterone dans la lignée cellulaire de cellules principales du tubule collecteur cortical (CCD) mpkCCDc14, suggérant que GILZ est un médiateur potentiel de la réponse à l'aldosterone. La co-expression in vitro de GILZ et du canal à Na+ sensible à l'amiloride ENaC dans le système d'expression de l'oocyte de Xénope a montré que GILZ n'a pas d'effet sur les courants sodiques véhiculées par ENaC en conditions basales. Une souris knock-out conditionnelle de GILZ est en train d'être produite et permettra l'étude in vivo de son rôle dans le rein et d'autres organes. Des expériences préliminaires ont montré que l'insuline induit un transport transépithelial de Na+ à des concentrations supraphysiologiques. L'insuline et l'insulin-like growth factor 1 (IGF-1) peuvent se lier à leurs récepteurs réciproques avec une affinité 50 à 100 fois moindre qu'à leur propre récepteur. Nous avons donc proposé que l'effet de l'insuline soit médié par le récepteur à l'IGF type 1 (IGF-1R). Dans une nouvelle lignée cellulaire qui présente toutes les caractéristiques des cellules principales du CCD (mCCDc11) nous avons montré que les deux hormones induisent une augmentation physiologiquement significative du transport du Na+ par l'activation des IGF-1 R. Aldosterone et insuline/IGF-1 ont un effet additif sur le transport de Na+, via l'activation de la voie de la PI3-kinase et la phosphorylation de la serum- and glucocorticoid-induced kinase 1 (Sgk1) par l'IGF-1R, dont l'expression est induite par l'aldosterone. Sgk1 intègre les effets de l'insuline et l'aldosterone. Nous proposons que l'IGF-1 joue un rôle dans la modulation physiologique de la balance sodique, tandis que l'insuline régule le transport de Na+ à des concentrations supraphysiologiques. Les deux hormones agissent en se liant à l'IGF-1R et induisent le transport de Na+ en activant la cascade de signalisation PI3-K - PDK1/2 - Sgk1. Nous avons montré pour la première fois que Sgk1 est exprimée et phosphorylée dans des conditions basales dans les cellules principales du CCD, mais le mécanisme qui maintient sa phosphorylation n'est pas connu. Ce nouveau rôle pour l'IGF-1 suggère qu'il pourrait être un gène impliqué de susceptibilité au sel. Aussi, l'IGF-1 stimule le transport rénal de Na+ in vivo. De plus, 35 % des patients atteints d'acromégalie (surproduction d'hormone de croissance et d'IGF-1) sont hypertensifs (prévalence plus élevée que la population normale), et des analyses génétiques suggèrent un lien entre le locus du gène de l'IGF-1 et la pression sanguine. RÉSUMÉ GRAND PUBLIC Nos ancêtres se sont génétiquement adaptés pendant des centaines de millénaires à un environnement pauvre en sel (chlorure de sodium) dans la savane équatoriale, où ils consommaient moins de 0,1 gramme de sel par jour. On a commencé à ajouter du sel aux aliments avec l'apparition de l'agriculture (il y a 5000 à 10000 années), et aujourd'hui une diète omnivore, qui inclut des plats préparés, contient plusieurs fois la quantité de sodium nécessaire pour notre fonction physiologique normale (environ 10 grammes par jour). Le corps garde sa concentration constante dans le sang en s'adaptant à une consommation très variable de sel. Pour ceci, il module son excrétion soit directement, soit en sécrétant des hormones régulatrices. Le rein joue un rôle principal dans cette régulation puisque l'excrétion urinaire de sel change selon la diète et peut aller d'une quantité dérisoire à plus de 36 grammes par jour. L'attention qu'on prête au sel est liée à sa relation avec l'hypertension essentielle. Ainsi, le contrôle rénal de l'excrétion de sodium et d'eau est le principal mécanisme dans la régulation de la pression sanguine, et une ingestion excessive de sel pourrait être l'un des facteurs-clé déclenchant l'apparition d'un phénotype hypertensif. L'hormone aldosterone diminue l'excrétion de sodium par le rein en modulant l'expression de gènes qui pourraient être impliqués dans la sensibilité au sel. Dans une lignée cellulaire de rein l'expression du gène TSC22D3, qui se traduit en la protéine Glucocorticoid Induced Leucine Zipper (GILZ), est fortement induite par l'aldosterone. Ceci suggère que GILZ est un médiateur potentiel de l'effet de l'aldosterone, et pourrait être impliqué dans la sensibilité au sel. Pour analyser la fonction de GILZ dans le rein plusieurs approches ont été utilisées. Par exemple, une souris dans laquelle GILZ est spécifiquement inactivé dans le rein est en train d'être produite et permettra l'étude du rôle de GILZ dans l'organisme. De plus, on a montré que GILZ, en conditions basales, n'a pas d'effet direct sur la protéine transportant le sodium à travers la membrane des cellules, le canal sodique épithélial ENaC. On a aussi essayé de trouver des protéines qui interagissent directement avec GILZ utilisant une technique appelée du « double-hybride dans la levure », mais aucun candidat n'a émergé. Des études ont montré que, à de hautes concentrations, l'insuline peut aussi diminuer l'excrétion de sodium. A ces concentrations, elle peut activer son récepteur spécifique, mais aussi le récepteur d'une autre hormone, l'Insulin-Like Growth Factor 1 (IGF-1). En plus, l'infusion d'IGF-1 augmente la rétention rénale de sodium et d'eau, et des mutations du gène codant pour l'IGF-1 sont liées aux différents niveaux de pression sanguine. On a utilisé une nouvelle lignée cellulaire de rein développée dans notre laboratoire, appelée mCCDc11, pour analyser l'importance relative des deux hormones dans l'induction du transport de sodium. On a montré que les deux hormones induisent une augmentation significative du transport de sodium par l'activation de récepteurs à l'IGF-1 et non du récepteur à l'insuline. On a montré qu'à l'intérieur de la cellule leur activation induit une augmentation du transport sodique par le biais du canal ENaC en modifiant la quantité de phosphates fixés sur la protéine Serumand Glucocorticoid-induced Kinase 1 (Sgk1). On a finalement montré que l'IGF-1 et l'aldosterone ont un effet additif sur le transport de sodium en agissant toutes les deux sur Sgk1, qui intègre leurs effets dans le contrôle du transport de sodium dans le rein.

Spermatological characteristics of Pleurogenidae (Digenea) inferred from the ultrastructural study of Pleurogenes claviger, Pleurogenoides medians and Prosotocus confusus

The present work constitutes the first ultrastructural analysis of the spermatozoon in the Pleurogenidae, with the study of three species belonging to three of the 16 genera included in this family, namely Pleurogenes claviger, Pleurogenoides medians and Prosotocus confusus. The mature spermatozoa of these pleurogenids present two axonemes of the 9+'1' trepaxonematan pattern, a nucleus, two mitochondria, two bundles of parallel cortical microtubules, external ornamentation, spine-like bodies and granules of glycogen. The organization of these characters in the sperm cell is similar in the three species. Thus, the anterior spermatozoon extremity is filiform and a continuous and submembranous layer of parallel cortical microtubules surrounds the axonemes at their anterior end. The posterior spermatozoon extremity exhibits the second axoneme and corresponds to the Cryptogonimidean type of Quilichini et al. (2010). Slight differences were noted between the spermatozoon of P. confusus and those of the two remaining species in the location of mitochondria.

Beta-catenin Status in P?aediatric Medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics.

Medulloblastoma is the most frequent malignant paediatric brain tumour. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favourable patient outcome. We report a series of 72 paediatric medulloblastomas evaluated for beta-catenin protein expression, CTNNB1 mutations, and comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumour cells) in six cases and focal nuclear staining (<10% of cells) in three cases. The other cases either exhibited a signal strictly limited to the cytoplasm (58 cases) or were negative (five cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented strong activation of the Wnt/beta-catenin pathway. Remarkably, five out of these six tumours showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumours with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2 months) from diagnosis. All three patients with focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumours represent a distinct molecular subgroup of medulloblastomas with favourable outcome, indicating that therapy de-escalation should be considered. International consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved.