Quantification of Myocardial Perfusion Using 13N-ammonia PET: a Cross-Comparison Study on Analysis Software Packages - Carimas, PMOD and FlowQuant

Aim. Several software packages (SWP) and models have been released for quantification of myocardial perfusion (MP). Although they all are validated against something, the question remains how well their values agree. The present analysis focused on cross-comparison of three SWP for MP quantification of 13N-ammonia PET studies. Materials & Methods. 48 rest and stress MP 13N-ammonia PET studies of hypertrophic cardiomyopathy (HCM) patients (Sciagrà et al., 2009) were analysed with three SW packages - Carimas, PMOD, and FlowQuant - by three observers blinded to the results of each other. All SWP implement the one-tissue-compartment model (1TCM, DeGrado et al. 1996), and first two - the two-tissue-compartment model (2TCM, Hutchins et al. 1990) as well. Linear mixed model for the repeated measures was fitted to the data. Where appropriate we used Bland-Altman plots as well. The reproducibility was assessed on global, regional and segmental levels. Intraclass correlation coefficients (ICC), differences between the SWPs and between models were obtained. ICC≥0.75 indicated excellent reproducibility, 0.4≤ICC<0.75 indicated fair to good reproducibility, ICC<0.4 - poor reproducibility (Rosner, 2010). Results. When 1TCM MP values were compared, the SW agreement on global and regional levels was excellent, except for Carimas vs. PMOD at RCA: ICC=0.715 and for PMOD vs. FlowQuant at LCX:ICC=0.745 which were good. In segmental analysis in five segments: 7,12,13, 16, and 17 the agreement between all SWP was excellent; in the remaining 12 segments the agreement varied between the compared SWP. Carimas showed excellent agreement with FlowQuant in 13 segments and good in four - 1, 5, 6, 11: 0.687≤ICCs≤0.73; Carimas had excellent agreement with PMOD in 11 segments, good in five_4, 9, 10, 14, 15: 0.682≤ICCs≤0.737, and poor in segment 3: ICC=0.341. PMOD had excellent agreement with FlowQuant in eight segments and substantial-to-good in nine_1, 2, 3, 5, 6,8-11: 0.585≤ICCs≤0.738. Agreement between Carimas and PMOD for 2TCM was good at a global level: ICC=0.745, excellent at LCX (0.780) and RCA (0.774), good at LAD (0.662); agreement was excellent for ten segments, fair-to-substantial for segments 2, 3, 8, 14, 15 (0.431≤ICCs≤0.681), poor for segments 4 (0.384) and 17 (0.278). Conclusions. The three SWP used by different operators to analyse 13N-ammonia PET MP studies provide results that agree well at a global level, regional levels, and mostly well even at a segmental level. Agreement is better for 1TCM. Poor agreement at segments 4 and 17 for 2TCM needs further clarification.

Genetic parameters and simultaneous selection for root yield, adaptability and stability of cassava genotypes

The objective of this work was to estimate genetic parameters and to evaluate simultaneous selection for root yield and for adaptability and stability of cassava genotypes. The effects of genotypes were assumed as fixed and random, and the mixed model methodology (REML/Blup) was used to estimate genetic parameters and the harmonic mean of the relative performance of genotypic values (HMRPGV), for simultaneous selection purposes. Ten genotypes were analyzed in a complete randomized block design, with four replicates. The experiment was carried out in the municipalities of Altamira, Santarém, and Santa Luzia do Pará in the state of Pará, Brazil, in the growing seasons of 2009/2010, 2010/2011, and 2011/2012. Roots were harvested 12 months after planting, in all tested locations. Root yield had low coefficients of genotypic variation (4.25%) and broad-sense heritability of individual plots (0.0424), which resulted in low genetic gain. Due to the low genotypic correlation (0.15), genotype classification as to root yield varied according to the environment. Genotypes CPATU 060, CPATU 229, and CPATU 404 stood out as to their yield, adaptability, and stability.

Mapping genetic variants associated with beta-adrenergic responses in inbred mice.

β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS) addressing the values and susceptibility of cardiovascular-related traits to a selective β(1)-blocker, Atenolol (ate), and a β-agonist, Isoproterenol (iso). The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA), a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG) values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP) to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8)). An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6)). Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD). Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort.

PURPOSE: Huntington's disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression. METHODS: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score. RESULTS: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41 ± 0.17 units per year vs. risperidone and 0.54 ± 0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05). CONCLUSIONS: Antipsychotics are widely used to treat patients with Huntington's disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores.

Kaasun jakauma paineellisissa sulpunkäsittelylaitteissa

Työn tarkoituksena oli tutkia kuinka kaasukuplat jakautuvat sellususpensioon, kun prosessiolosuhteita muutetaan. Kuplien kokojakauman avulla pyritään kartoittamaan kuinka kaasukuplat pilkkoutuvat ja onko olemassa raja-arvoa, milloin tehon lisäys ei enää pilko sellususpensiossa olevia kuplia pienemmiksi. Jakaumien avulla voidaan mahdollisesti kehittää kaasunpoistoa. Työssä selvitettiin voidaanko kameratekniikkaa käyttää kuplakokojen määrittämiseen sellusulpusta. Läpinäkymätön sellumassa tarjoaa kuvaukselle haasteellisen ympäristön. Myöskään kirjallisuudessa ei vastaavaa menetelmää aikaisemmin oltu käytetty. Kuvatusta materiaalista laskettiin kuplien halkaisijat, joita pyrittiin tarkastelemaan tilastollisesti. Tilastollinen tarkastelu toi eroja mittauspisteiden välille. Kuplien halkaisijoiden perusteella mallinnettiin kuplakokoon vaikuttavat prosessisuureet lineaarisella regressioanalyysillä. Mallinnuksen perusteella saatiinvasteisiin vaikuttavat riippumattomat muuttujat ja niiden matemaattiset malliyhtälöt. Tuloksina saatiin selville, että kuplien kokojakaumissa on eroja sekoitussäiliön eri puolilla. Sekoitussäiliössä suurten kuplien suhteellinen osuus kasvaa kaasupitoisuuden ja sakeuden noustessa. Mallinnuksen tärkeimpänä tuloksena voidaan todeta, että sakeus ja kaasutilavuus vaikuttavat kuplakokoon kasvattavasti. Kierrosnopeuden kasvattaminen pienentää kuplakokoa. Visuaalisen informaation avulla on helpompi ymmärtää kuinka kuplat käyttäytyvät.

Selection response of growth rate in rabbits for meat production

Genetic and environmental trends in 2 lines of rabbit (B and R) selected on individual weight gain (WG) from weaning (4 wk) to slaughter (11 wk) were estimated using mixed model methodology. Line B was derived from the California breed and line R was a synthetic of stock of different origin. The data were collected from a single herd and comprised 7 718 individuals in line B and 9 391 in line R, the lines having 12 and 9 generations of selection respectively. Realized responses in the 2 lines were 2.7% and 2.2% of the initial mean per year respectively and showed that selection on WG was effective but was less than expected. Selection on slaughter weight (SW) and effects of selection on other economic traits are discussed. It is concluded that selection on either WG or SW is a simple method for improving growth rate in rabbit sire line stocks.

Clinical effectiveness of direct anterior restorations-A meta-analysis.

OBJECTIVES: This is the first meta-analysis on the efficacy of composite resin restorations in anterior teeth. The objective of the present meta-analysis was to verify whether specific material classes, tooth conditioning methods and operational procedures influence the result for Class III and Class IV restorations. MATERIAL AND METHODS: The database SCOPUS and PubMed were searched for clinical trials on anterior resin composites without restricting the search to the year of publication. The inclusion criteria were: (1) prospective clinical trial with at least 2 years of observation; (2) minimal number of restorations at last recall=20; (3) report on drop-out rate; (4) report of operative technique and materials used in the trial, and (5) utilization of Ryge or modified Ryge evaluation criteria. For the statistical analysis, a linear mixed model was used with random effects to account for the heterogeneity between the studies. p-Values smaller than 0.05 were considered to be significant. RESULTS: Of the 84 clinical trials, 21 studies met the inclusion criteria, 14 of them for Class III restorations, 6 for Class IV restorations and 1 for closure of diastemata; the latter was included in the Class IV group. Twelve of the 21 studies started before 1991 and 18 before 2001. The estimated median overall success rate (without replacement) after 10 years for Class III composite resin restorations was 95% and for Class IV restorations 90%. The main reason for the replacement of Class IV restorations was bulk fractures, which occurred significantly more frequently with microfilled composites than with hybrid and macrofilled composites. Caries adjacent to restorations was infrequent in most studies and accounted only for about 2.5% of all replaced restorations after 10 years irrespective of the cavity class. Class III restorations with glass ionomer derivates suffered significantly more loss of anatomical form than did fillings with other types of material. When the enamel was acid-etched and no bonding agent was applied, significantly more restorations showed marginal staining and detectable margins compared to enamel etching with enamel bonding or the total etch technique; fillings with self-etching systems were in between of these two outcome variables. Bevelling of the enamel was associated with a significantly reduced deterioration of the anatomical form compared to no bevelling but not with less marginal staining or less detectable margins. The type of isolation (absolute/relative) had a statistically significant influence on marginal caries which, however, might be a random finding.

Sellun jälkilajittelun kehittäminen

Työn tavoitteena oli löytää painelajittimen roottorin keskeiset muuttujat ja ajoparametrit, kun pyritään jälkilajittelemaan valkaistua sellumassaa korkeassa sakeudessa, sekä näiden vaikutukset. Tavoitteena oli teknisesti onnistunut lajittelu korkeassa sakeudessa siten, että laitteen puhdistustehokkuus on hyvä, ominaisenergian kulutus on pieni ja kapasiteetti on korkea. Ensin tarkasteltiin kuitenkin teoreettisesti valkaistun sellumassan painelajittelun ongelmakenttää, keskeisten epäpuhtauksien poistoa jälkilajittelussa ja vertailtiin korkea- ja matalasakeuslajittelua. Lisäksi esiteltiin yleisellä tasolla koesuunnittelumenetelmien periaatteita ja menetelmiä sekä analyysiä so. mallinnus. Tätä taustaa vasten haluttiin myös kartoittaa ja esitellä painelajittimen keskeinen muuttujakenttä. Tämän jälkeen selvitettiin kokeellisesti miten ajettavan valkaistun mäntysellumassan sakeus, roottorin kehänopeus ja roottorin rakenteen muutokset vaikuttavat painelajittimen kapasiteettiin, rejektin sakeutumiskertoimeen, ominaisenergian kulutukseen ja puhdistustehokkuuteen. Vaikutusten ja parhaan roottorirakenteen sekä ajosuureiden määritys suoritettiin mallintamalla mittaustulokset lineaarisella regressioanalyysilla. Saatiin tärkeimmät vasteisiin vaikuttavat riippumattomat muuttujat ja niiden matemaattiset esityk-set, malliyhtälöt. Mallinnusta hyväksi käyttäen tarkasteltiin vielä erikseen yhden roottorin ajoa. Tärkeimpinä tuloksina saatiin selville, että puhdistustehokkuus on lähes vakio tietyllä roottorirakenteella riippumatta sakeudesta ja roottorin kehänopeudesta. Edullista puhdistustehokkuuden kannalta on käyttää ensisijaisesti isoa roottorin palaelementin korkeutta ja välystä suhteessa sihtirumpuun. Jälkilajittelu painelajittimella korkeassa sakeudessa kannattaa suorittaa pienellä roottorin kehänopeudella, runko- ja palaelementtivälyksellä suhteessa sihtirumpuun sekä suurella palaelementin korkeudella. Tällöin saavutetaan hyvä kompromissi ominaisenergian kulutuksen ja laitteen ajettavuuden osalta. Iso elementin korkeus ja pieni elementtivälys eivät aja massaa tehokkaasti laitteen alaosaan. Tällöin ei pyöritetä myöskään suurta massamäärää. Pieni elementtivälys mahdollistaa myös massan tehokkaamman leikkauksen, joka parantaa fluidisoitumista. Kitkavoimat ovat luonnollisesti ko. olosuhteissa suuremmat, joten ominais-energian kulutus kasvaa jonkin verran. Ratkaisevinta ominaisenergian kulutuksen kannalta on kuitenkin ajaa laitetta pienellä kehänopeudella.

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide.

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide.

Meta-analysis of the influence of bonding parameters on the clinical outcome of tooth-colored cervical restorations

PURPOSE: To meta-analyze the literature on the clinical performance of Class V restorations to assess the factors that influence retention, marginal integrity, and marginal discoloration of cervical lesions restored with composite resins, glass-ionomer-cement-based materials [glass-ionomer cement (GIC) and resin-modified glass ionomers (RMGICs)], and polyacid-modified resin composites (PMRC). MATERIALS AND METHODS: The English literature was searched (MEDLINE and SCOPUS) for prospective clinical trials on cervical restorations with an observation period of at least 18 months. The studies had to report about retention, marginal discoloration, marginal integrity, and marginal caries and include a description of the operative technique (beveling of enamel, roughening of dentin, type of isolation). Eighty-one studies involving 185 experiments for 47 adhesives matched the inclusion criteria. The statistical analysis was carried out by using the following linear mixed model: log (-log (Y /100)) = β + α log(T ) + error with β = log(λ), where β is a summary measure of the non-linear deterioration occurring in each experiment, including a random study effect. RESULTS: On average, 12.3% of the cervical restorations were lost, 27.9% exhibited marginal discoloration, and 34.6% exhibited deterioration of marginal integrity after 5 years. The calculation of the clinical index was 17.4% of failures after 5 years and 32.3% after 8 years. A higher variability was found for retention loss and marginal discoloration. Hardly any secondary caries lesions were detected, even in the experiments with a follow-up time longer than 8 years. Restorations placed using rubber-dam in teeth whose dentin was roughened showed a statistically significantly higher retention rate than those placed in teeth with unprepared dentin or without rubber-dam (p < 0.05). However, enamel beveling had no influence on any of the examined variables. Significant differences were found between pairs of adhesive systems and also between pairs of classes of adhesive systems. One-step self-etching had a significantly worse clinically index than two-step self-etching and three-step etch-and-rinse (p = 0.026 and p = 0.002, respectively). CONCLUSION: The clinical performance is significantly influenced by the type of adhesive system and/or the adhesive class to which the system belongs. Whether the dentin/enamel is roughened or not and whether rubberdam isolation is used or not also significantly influenced the clinical performance. Composite resin restorations placed with two-step self-etching and three-step etch-and-rinse adhesive systems should be preferred over onestep self-etching adhesive systems, GIC-based materials, and PMRCs.

La llibertat condicional a Catalunya

La recerca analitza quines són les claus actuals de l’ús dela LCa Catalunya. Per fer-ho, primer de tot explica quina és la realitat de les polítiques criminals i d’execució penal practicades a Catalunya i a Espanya i les compara amb altres realitats europees. Els resultats d’aquesta primera part fonamenten la conveniència de fer augmentar de manera significativa la seva aplicació i com aquest augment repercutiria positivament en la millora de les taxes de reincidència, en el desistiment del delicte i en la reinserció social de les persones encarcerades. En la segona part de l’estudi s’analitza el perfil de les persones que arriben a la LC però també de les que no hi arriben, tot i complir algunes de les condicions objectives per fer-ho. De l’estudi d’aquests perfils s’analitzen les similituds i diferències en les característiques dels penats i es fan propostes de millora en la classificació de grau penitenciari i la possibilitat de progressió sense que augmenti el risc teòric de reincidència ni el de recursos a assignar, tot i que sí resulti necessari pensar i fer-ne una redistribució dels actualment existents. La tercera part de l’estudi es dedica a analitzar els obstacles que té l’Administració per poder fer propostes de millora per augmentar la seva implementació. Entre les dificultats analitzades es comenten: el model d’aplicació espanyol sobre la LC, la satisfacció de la responsabilitat civil, els estrangers que es troben en situació administrativa irregular a Espanya, els retards en la concessió dels permisos ordinaris i les progressions de grau i el seguiment i control de la LC. L’estudi ha fet servir metodologies quantitatives i qualitatives simultàniament. La informació obtinguda es triangula i s’assenyalen aquells punts on el consens és més global i aquells punts més controvertits on els resultats no permeten extreure’n conclusions fefaents. En la part quantitativa s’han analitzat utilitzant diferents tècniques estadístiques 3.340 casos que es trobaven l’any 2012 en LC, 3r grau i 2n grau. En la part qualitativa, s’ha fet anàlisi de casos, entrevistes en profunditat, grups focals, tècnica Delphi i recull bibliogràfic i de legislació comparada. La recerca acaba proposant 23 propostes de millora agrupades en 6 blocs d’intervenció.

La libertad condicional en Cataluña

La investigación analiza cuáles son las claves actuales del uso de la libertad condicional (LC) en Cataluña. Para hacerlo, primero explica cuáles son las realidades de las políticas criminales y de ejecución penal practicadas en Cataluña y España y las compara con otras realidades europeas. Los resultados de esta primera parte fundamentan la conveniencia de aumentar de manera significativa su aplicación y cómo este aumento repercutiría positivamente en la mejora de las tasas de reincidencia, en el desistimiento del delito y en la reinserción social de las personas encarceladas. En la segunda parte del estudio se analiza el perfil de las personas que llegan a LC, pero también de las que no llegan, a pesar de cumplir algunas de las condiciones objetivas para hacerlo. Del estudio de estos perfiles se analizan las similitudes y diferencias en las características de los penados y se hacen propuestas de mejora en la clasificación de grado penitenciario y la posibilidad de progresión sin que aumente el riesgo teórico de reincidencia ni el de recursos a asignar, aunque sí hacer una redistribución de los actualmente existentes. La tercera parte del estudio analiza los obstáculos que tiene la Administración para poder hacer propuestas de mejora para aumentar la aplicación de la LC. Entre las dificultades analizadas se comentan: el modelo de aplicación español sobre la LC, la satisfacción de la responsabilidad civil, los extranjeros que se encuentran en situación administrativa irregular en España, los retrasos en la concesión de los permisos ordinarios y las progresiones de grado y el seguimiento y control de la LC. El estudio ha utilizado metodologías cuantitativas y cualitativas simultáneamente. La información obtenida se triangula y se señalan aquellos puntos donde el consenso es más global y aquellos puntos más controvertidos donde los resultados no permiten extraer conclusiones fehacientes. En la parte cuantitativa se han analizado 3.340 casos que se encontraban en 2012 en LC, 3 º grado y 2 º grado utilizando diferentes técnicas estadísticas. En la parte cualitativa, se han hecho análisis de casos, entrevistas en profundidad, grupos focales, técnica Delphi y recopilación bibliográfica y de legislación comparada. La investigación termina proponiendo 23 propuestas de mejora agrupadas en 6 bloques de intervención.

The effect of skewness and kurtosis on the Kenward-Roger approximation when group distributions differ

This study examined the independent effect of skewness and kurtosis on the robustness of the linear mixed model (LMM), with the Kenward-Roger (KR) procedure, when group distributions are different, sample sizes are small, and sphericity cannot be assumed. Methods: A Monte Carlo simulation study considering a split-plot design involving three groups and four repeated measures was performed. Results: The results showed that when group distributions are different, the effect of skewness on KR robustness is greater than that of kurtosis for the corresponding values. Furthermore, the pairings of skewness and kurtosis with group size were found to be relevant variables when applying this procedure. Conclusions: With sample sizes of 45 and 60, KR is a suitable option for analyzing data when the distributions are: (a) mesokurtic and not highly or extremely skewed, and (b) symmetric with different degrees of kurtosis. With total sample sizes of 30, it is adequate when group sizes are equal and the distributions are: (a) mesokurtic and slightly or moderately skewed, and sphericity is assumed; and (b) symmetric with a moderate or high/extreme violation of kurtosis. Alternative analyses should be considered when the distributions are highly or extremely skewed and samples sizes are small.

Impact of body tilt on the central aortic pressure pulse.

The present work was undertaken to investigate, in young healthy volunteers, the relationships between the forward propagation times of arterial pressure waves and the timing of reflected waves observable on the aortic pulse, in the course of rapid changes in body position. 20 young healthy subjects, 10 men, and 10 women, were examined on a tilt table at two different tilt angles, -10° (Head-down) and + 45° (Head-up). In each position, carotid-femoral (Tcf) and carotid-tibial forward propagation times (Tct) were measured with the Complior device. In each position also, the central aortic pressure pulse was recorded with radial tonometry, using the SphygmoCor device and a generalized transfer function, so as to evaluate the timing of reflected waves reaching the aorta in systole (onset of systolic reflected wave, sT1r) and diastole (mean transit time of diastolic reflected wave, dMTT). The position shift from Head-up to Head-down caused a massive increase in both Tct (women from 130 ± 10 to 185 ± 18 msec P < 0.001, men from 136 ± 9 to 204 ± 18 msec P < 0.001) and dMTT (women from 364 ± 35 to 499 ± 33 msec P < 0.001, men from 406 ± 22 to 553 ± 21 msec P < 0.001). Mixed model regression showed that the changes in Tct and dMTT observed between Head-up and Head-down were tightly coupled (regression coefficient 2.1, 95% confidence interval 1.9-2.3, P < 0.001). These results strongly suggest that the diastolic waves observed on central aortic pulses reconstructed from radial tonometric correspond at least in part to reflections generated in the lower limbs.