Validation of 3D echocardiographic volume detection of left atrium by human cadaveric casts

Background: Left atrial volume is a prognostic factor in cardiac pathologies. We aimed to validate left atrial volume detection with 3D and 2D echocardiography (3DE and 2DE) by human cadaveric casts. 3DE facilitates measurement of atrial volume without geometrical assumptions or dependence on imaging angle in contrast to 2DE methods. Methods: For method validation, six water-filled balloons were submerged in a 20-l water tank and their volumes were measured with 3DE. Seven human cadaveric left atrial casts were prepared of silicone and were transformed into ultrasound-permeable casts. Casts were imaged in the same setting, so that 3DE and 2DE of casts represented transthoracic apical view. Left ventricle analysis softwares GE 4D Auto LVQ and TomTec 4D LV-Function were used for 3DE volumetry. Results; Balloon volumes ranged 37 to 255ml (mean 126 ml). 3DE resulted in an excellent volumetric agreement with balloon volumes, absolute bias was -3.7 ml (95% CI -5.9 to -1.4). Atrial cast volumes were 38 to 94 ml (mean 56.6 ml). 3DE and 2DE volumes were excellently correlated with cast volumes (r = 0.96 to 0.99). Biases were for GE 4D LVQ - 0.7 ml (95% CI -6.1 to 4.6), TomTec 4D LV-Function 3.3 ml (-1.9 to 8.5) and 2DE 2.9 ml (-4.0 to 9.9). 3DE resulted in lower limits of agreement and showed no volume-related bias in contrast to area-length method. Conclusions: We conclude that measurement of human cadaveric left atrial cast volumes by 3DE is in excellent agreement with true cast volumes.Peer reviewe

Initial treatment strategy and clinical outcomes in Finnish MS patients : a propensity-matched study

Background The optimal treatment strategy with disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) remains uncertain. Objective To compare outcomes of initial treatment with infusion therapies and starting therapy with medium efficacy therapy in a propensity-matched cohort of Finnish RRMS patients. Methods A total of 154 RRMS patients initiating natalizumab, alemtuzumab, ocrelizumab or rituximab as first DMT (high efficacy DMT, heDMT group) and 1771 patients initially treated with injectable therapies, teriflunomide or dimethylfumarate and escalated based on disease activity (moderate efficacy DMT, meDMT group) were identified from the Finnish MS registry. Nearest neighbor propensity matching (1:1, caliper 0.1) was performed for age, sex, baseline Expanded Disability Status Scale (EDSS), annual relapse rate (ARR) one year prior DMT and time since MS symptom onset. Primary outcome was time to 6-month confirmed EDSS progression and the secondary outcome time to first relapse. Results In the propensity-matched group comparisons, the probability of 6-month confirmed disability progression (CDP) at 5 years after DMT start was 28.4% (95% CI 15.7-39.3) in the heDMT group (n = 66) and 47.0% (95% CI 33.1-58.1) in meDMT group (n = 66), p = 0.013. Probability of relapse at 5 years was 34.6% (95% CI 24.1-43.6) for heDMT (n = 105) and 47.2% (95% CI 36.6-56.1) for meDMT (n = 105), p = 0.019. Conclusions Initiating MS-therapy with heDMT significantly reduced the risk of 5-year disability progression and relapse compared to using meDMT as first DMT choice in propensity-matched groups of Finnish MS-patients.Peer reviewe

Mindsets and Failures : Neural Differences in Reactions to Mistakes among 2nd Grade Finnish Girls

Mindsets have been identified as an important factor in explaining learning differences among students. Growth mindset students have been shown to recover from mistakes easier than fixed mindset students, and recent neuroscientific research has shown differences in the brain’s event-related potentials to errors in fixed and growth mindset participants. The purpose of this study was to examine and evaluate these differences in the Finnish elementary school context. To achieve this, event-related potentials of five fixed and five growth mindset 8-9-year-old female students were recorded during a go/no-go task. Differences between the two groups emerged, however, they were different from the results of some previous studies in the field. These findings are discussed in the light of earlier neuroscientific research related to mindsets, including limitations and suggestions for future research in the field.Peer reviewe

The ATF6-Met [67] Val substitution is associated with increased plasma cholesterol levels

Objective— Activating transcription factor 6 (ATF6) is a sensor of the endoplasmic reticulum stress response and regulates expression of several key lipogenic genes. We used a 2-stage design to investigate whether ATF6 polymorphisms are associated with lipids in subjects at increased risk for cardiovascular disease (CVD). Methods and Results— In stage 1, 13 tag-SNPs were tested for association in Dutch samples ascertained for familial combined hyperlipidemia (FCHL) or increased risk for CVD (CVR). In stage 2, we further investigated the SNP with the strongest association from stage 1, a Methionine/Valine substitution at amino-acid 67, in Finnish FCHL families and in subjects with CVR from METSIM, a Finnish population-based cohort. The combined analysis of both stages reached region-wide significance (P=9x10–4), but this association was not seen in the entire METSIM cohort. Our functional analysis demonstrated that Valine at position 67 augments ATF6 protein and its targets Grp78 and Grp94 as well as increases luciferase expression through Grp78 promoter. Conclusions— A common nonsynonymous variant in ATF6 increases ATF6 protein levels and is associated with cholesterol levels in subjects at increased risk for CVD, but this association was not seen in a population-based cohort. Further replication is needed to confirm the role of this variant in lipids. We report the association of the ATF6-methionine [67]valine amino-acid substitution with plasma cholesterol levels. Association analyses in 2674 subjects and functional data suggest that the ATF6 gene may influence cholesterol levels in subjects at increased risk to develop cardiovascular disease

Revisiting left atrial volumetry by magnetic resonance imaging : the role of atrial shape and 3D angle between left ventricular and left atrial axis

Background Accurate measurement of left atrial (LA) volumes is needed in cardiac diagnostics and the follow up of heart and valvular diseases. Geometrical assumptions with 2D methods for LA volume estimation contribute to volume misestimation. In this study, we test agreement of 3D and 2D methods of LA volume detection and explore contribution of 3D LA axis orientation and LA shape in introducing error in 2D methods by cardiovascular magnetic resonance imaging. Methods 30 patients with prior first-ever ischemic stroke and no known heart disease, and 30 healthy controls were enrolled (age 18-49) in a substudy of a prospective case-control study. All study subjects underwent cardiac magnetic resonance imaging and were pooled for this methodological study. LA volumes were calculated by biplane area-length method from both conventional long axis (LAV(AL-LV)) and LA long axis-oriented images (LAV(AL-LA)) and were compared to 3D segmented LA volume (LAV(SAX)) to assess accuracy of volume detection. 3D orientation of LA long axis to left ventricular (LV) long axis and to four-chamber plane were determined, and LA 3D sphericity indices were calculated to assess sources of error in LA volume calculation. Shapiro-Wilk test, Bland-Altman analysis, intraclass and Pearson correlation, and Spearman's rho were used for statistical analysis. Results Biases were - 9.9 mL (- 12.5 to - 7.2) for LAV(AL-LV) and 13.4 (10.0-16.9) for LAV(AL-LA) [mean difference to LAV(SAX) (95% confidence interval)]. End-diastolic LA long axis 3D deviation angle to LV long axis was 28.3 +/- 6.2 degrees [mean +/- SD] and LA long axis 3D rotation angle to four-chamber plane 20.5 +/- 18.0 degrees. 3D orientation of LA axis or 3D sphericity were not correlated to error in LA volume calculation. Conclusions Calculated LA volume accuracy did not improve by using LA long axis-oriented images for volume calculation in comparison to conventional method. We present novel data on LA axis orientation and a novel metric of LA sphericity and conclude that these measures cannot be utilized to assess error in LA volume calculation.Peer reviewe

Can processes make relationships work? The Triple Helix between structure and action

This contribution seeks to explore how complex adaptive theory can be applied at the conceptual level to unpack Triple Helix models. We use two cases to examine this issue – the Finnish Strategic Centres for Science, Technology & Innovation (SHOKs) and the Canadian Business-led Networks of Centres of Excellence (BL-NCE). Both types of centres are organisational structures that aspire to be business-led, with a considerable portion of their activities driven by (industrial) users’ interests and requirements. Reflecting on the centres’ activities along three dimensions – knowledge generation, consensus building and innovation – we contend that conceptualising the Triple Helix from a process perspective will improve the dialogue between stakeholders and shareholders

The host galaxies of z=7 quasars: predictions from the BlueTides simulation

We examine the properties of the host galaxies of $z=7$ quasars using the large volume, cosmological hydrodynamical simulation BlueTides. We find that the 10 most massive black holes and the 191 quasars in the simulation (with $M_{\textrm{UV,AGN}}<M_{\textrm{UV,host}}$) are hosted by massive galaxies with stellar masses $\log(M_\ast/M_\odot)=10.8\pm0.2$, and $10.2\pm0.4$, which have large star formation rates, of $513\substack{+1225 \\ -351}M_\odot/\rm{yr}$ and $191\substack{+288 \\ -120}M_\odot/\rm{yr}$, respectively. The hosts of the most massive black holes and quasars in BlueTides are generally bulge-dominated, with bulge-to-total mass ratio $B/T\simeq0.85\pm0.1$, however their morphologies are not biased relative to the overall $z=7$ galaxy sample. We find that the hosts of the most massive black holes and quasars are significantly more compact, with half-mass radii $R_{0.5}=0.41\substack{+0.18 \\ -0.14}$ kpc and $0.40\substack{+0.11 \\ -0.09}$ kpc respectively; galaxies with similar masses and luminosities have a wider range of sizes with a larger median value, $R_{0.5}=0.71\substack{+0.28 \\ -0.25}$ kpc. We make mock James Webb Space Telescope (JWST) images of these quasars and their host galaxies. We find that distinguishing the host from the quasar emission will be possible but still challenging with JWST, due to the small sizes of quasar hosts. We find that quasar samples are biased tracers of the intrinsic black hole--stellar mass relation, following a relation that is 0.2 dex higher than that of the full galaxy sample. Finally, we find that the most massive black holes and quasars are more likely to be found in denser environments than the typical $M_{\textrm{BH}}>10^{6.5}M_\odot$ black hole, indicating that minor mergers play at least some role in growing black holes in the early Universe.Comment: 19 pages, 20 figures. Accepted for publication in MNRA

First Light And Reionisation Epoch Simulations (FLARES) : IV. The size evolution of galaxies at z ≥ 5

We present the intrinsic and observed sizes of galaxies at z >= 5 in the First Light And Reionisation Epoch Simulations (flares). We employ the large effective volume of flares to produce a sizeable sample of high-redshift galaxies with intrinsic and observed luminosities and half-light radii in a range of rest-frame ultraviolet (UV) and visual photometric bands. This sample contains a significant number of intrinsically ultracompact galaxies in the far-UV (1500 angstrom), leading to a negative intrinsic far-UV size-luminosity relation. However, after the inclusion of the effects of dust these same compact galaxies exhibit observed sizes that are as much as 50 times larger than those measured from the intrinsic emission, and broadly agree with a range of observational samples. This increase in size is driven by the concentration of dust in the core of galaxies, heavily attenuating the intrinsically brightest regions. At fixed luminosity we find a galaxy size redshift evolution with a slope of m = 1.21-1.87 depending on the luminosity sample in question, and we demonstrate the wavelength dependence of the size-luminosity relation that will soon be probed by the James Webb Space Telescope.Peer reviewe