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Background and Aim: To study the relationships of cardiovascular risk factors with cancer and cardiovascular mortality in a cohort of middle-aged men followed-up for 61 years., Materials and Methods: A rural cohort of 1611 cancer- and cardiovascular disease-free men aged 40-59 years was examined in 1960 within the Italian Section of the Seven Countries Study, and 28 risk factors measured at baseline were used to predict cancer ( n = 459) and cardiovascular deaths ( n = 678) that occurred during 61 years of follow-up until the extinction of the cohort with Cox proportional hazard models., Results: A model with 28 risk factors and cancer deaths as the end-point produced eight statistically significant coefficients for age, smoking habits, mother early death, corneal arcus, xanthelasma and diabetes directly related to events, and arm circumference and healthy diet inversely related. In the corresponding models for major cardiovascular diseases and their subgroups, only the coefficients of age and smoking habits were significant among those found for cancer deaths, to which healthy diet can be added if considering coronary heart disease alone. Following a competing risks analysis by the Fine-Gray method, risk factors significantly common to both conditions were only age, smoking, and xanthelasma., Conclusions: A sizeable number of traditional cardiovascular risk factors were not predictors of cancer death in a middle-aged male cohort followed-up until extinction.

Purpose: To study a male Italian cohort (initially aged 40-59, n = 1712) during 61 years and the natural history of major CVD mortality categories including coronary heart disease (CHD), stroke and other heart diseases of uncertain etiology (HDUE), including congestive heart failure) along with their risk factor relationships., Methods and Results: Cox models were run with 12 covariates as possible predictors measured at entry to the study. About 93% of all CVD deaths were covered by the three major groups selected here (N = 751): 37.4% of them were diagnosed as CHD, 30.6% as stroke and 28.5% as HDUE. CHD declined in the last 20 years of follow-up, while a sharp increase in HDUE mortality was seen. Baseline mean levels of serum cholesterol were 209.6, 204.2 and 198.0 mg/dL, respectively, for CHD, stroke and HDUE deaths: the multivariable coefficients of serum cholesterol were positive and significant for CHD ( p < 0.0001), and stroke ( p = 0.0203) and not significant for HDUE ( p = 0.3467). In Fine-Gray models, the algebraic signs of cholesterol coefficients were opposite for CHD versus the other mortality categories (t = 3.13). The predictive performances of remaining risk factors were varied whereas that of Cox models was not very good, probably due to the attrition phenomenon and possible competing risks., Conclusion: Large differences in natural history and risk factors were found comparing the three CVD conditions, potentially indicating different etiologies and pointing to the need of not mixing them up in a grouped CVD category.

Background: Infant crying is the first attempt babies use to communicate during their initial months of life. A misunderstanding of the cry message can compromise infant care and future neurodevelopmental process., Methods: An exploratory study collecting multimodal data (i.e., crying, electroencephalography (EEG), near-infrared spectroscopy (NIRS), facial expressions, and body movements) from 38 healthy full-term newborns was conducted. Cry types were defined based on different conditions (i.e., hunger, sleepiness, fussiness, need to burp, and distress). Statistical analysis, Machine Learning (ML), and Deep Learning (DL) techniques were used to identify relevant features for cry type classification and to evaluate a robust DL algorithm named Acoustic MultiStage Interpreter (AMSI)., Results: Significant differences were found across cry types based on acoustics, EEG, NIRS, facial expressions, and body movements. Acoustics and body language were identified as the most relevant ML features to support the cause of crying. The DL AMSI algorithm achieved an accuracy rate of 92%., Conclusions: This study set a precedent for cry analysis research by highlighting the complexity of newborn cry expression and strengthening the potential use of infant cry analysis as an objective, reliable, accessible, and non-invasive tool for cry interpretation, improving the infant-parent relationship and ensuring family well-being., Competing Interests: Declaration of competing interest The authors declare competing interests (Funding, Employment or Confidentiality interests) in relation to the work described herein. Ana Laguna, Sandra Pusil, Àngel Bazán and Paolo Piras are employed by Zoundream AG. Ana Laguna is also a co-founder of the company and owns stock in Zoundream AG. Silvia Orlandi, Alexandra Pardos Véglia and Jonathan Adrian Zegarra-Valdivia receive compensation for the collaboration as members of the scientific advisory board of Zoundream AG. Clàudia Palomares’ salary is funded by Zoundream AG through Fundació Clínic. Anna Lucia Paltrinieri and Oscar Garcia-Algar declare no potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess whether competing risks help explain why regions with initially high serum cholesterol have higher mortality from coronary heart disease (CHD) and lower mortality from stroke and other major heart diseases, while the reverse is found for those with initially lower serum cholesterol., Material and Methods: Ten cohorts of men (N = 9063) initially aged 40-59 in six countries were examined and followed for fatal outcomes for 60 years. Major cardiovascular disease (CVD) groups were CHD, stroke, and other Heart Diseases of Uncertain Etiology (HDUE), or the combination of stroke and HDUE (STHD), along with all other causes of death. Fine-Gray competing risk analysis was applied with CHD versus all other causes of death or STHD (direct mode) and all other causes of death or STHD versus CHD (inverse mode), and the effects of 19 covariates (of which 3 references) on the cause-specific hazard of the outcomes were assessed, thus investigating potential etiologic roles. A systematic comparison with results obtained by running the Cox model in direct and inverse modes with the same end-point results was also performed and illustrated graphically., Results: CHD mortality is bound to different risk factor relationships when compared with all other causes of death and with STHD. The role of serum cholesterol is crucial since, in both comparisons, by Fine-Gray, its coefficients are positive and significant for CHD and negative and significant for all other causes of death and STHD. Risk factor capabilities in specific outcome types of the CVD domain (CHD versus STHD) are different depending on the outcome types considered. Risk factor coefficients are smaller in Fine-Gray modelling and larger in the Cox model. Fine-Gray detects different risk factors whose coefficients may have opposite algebraic signs., Conclusions: This is the first report whereby a large group of risk factors are investigated in connection with life-long CVD outcomes by Fine-Gray competing risk analysis, and a systematic comparison is performed with results obtained by Cox models in both direct and inverse modes. Subtypes of CVD mortality should be summed with full awareness that some risk factors vary by pathology, and they should at least be disentangled into CHD and STHD.

Introduction: Even though infant crying is a common phenomenon in humans' early life, it is still a challenge for researchers to properly understand it as a reflection of complex neurophysiological functions. Our study aims to determine the association between neonatal cry acoustics with neurophysiological signals and behavioral features according to different cry distress levels of newborns., Methods: Multimodal data from 25 healthy term newborns were collected simultaneously recording infant cry vocalizations, electroencephalography (EEG), near-infrared spectroscopy (NIRS) and videos of facial expressions and body movements. Statistical analysis was conducted on this dataset to identify correlations among variables during three different infant conditions (i.e., resting, cry, and distress). A Deep Learning (DL) algorithm was used to objectively and automatically evaluate the level of cry distress in infants., Results: We found correlations between most of the features extracted from the signals depending on the infant's arousal state, among them: fundamental frequency (F0), brain activity (delta, theta, and alpha frequency bands), cerebral and body oxygenation, heart rate, facial tension, and body rigidity. Additionally, these associations reinforce that what is occurring at an acoustic level can be characterized by behavioral and neurophysiological patterns. Finally, the DL audio model developed was able to classify the different levels of distress achieving 93% accuracy., Conclusion: Our findings strengthen the potential of crying as a biomarker evidencing the physical, emotional and health status of the infant becoming a crucial tool for caregivers and clinicians., Competing Interests: AL, SP, ÀB, and PP were employed by Zoundream AG. AL is also co-founder of the company and owns stock in Zoundream AG. SO and JZ-V receive compensation for the collaboration as members of the scientific advisory board of Zoundream AG. CP salary is funded by Zoundream AG through Fundació Clínic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Laguna, Pusil, Acero-Pousa, Zegarra-Valdivia, Paltrinieri, Bazán, Piras, Palomares i Perera, Garcia-Algar and Orlandi.)

The directions of primary strain lines of local deformation in Epicardial and Endocardial layers have been the subject of debate in recent years. Different methods led to different conclusions and a complete assessment of strain direction patterns in large and variable (in terms of pathology) cohorts of healthy and diseased patients is still lacking. Here, we use local deformation tensors in order to evaluate the angle of strain lines with respect to the horizontal circumferential direction in both Epi- and Endo-layers. We evaluated this on a large group of 193 subjects including 82 healthy control and 111 patients belonging to a great variety of pathological conditions. We found that Epicardial strain lines obliquely directed while those of Endocardium are almost circumferential. This result occurs irrespective of pathological condition. We propose that the geometric vinculum characterizing Endocardium and Epicardium in terms of different lever arm length and orientation of muscular fibers during contraction inescapably requires Endocardial strain lines to be circumferentially oriented and this is corroborated by experimental results. Further investigations on transmural structure of myocytes could couple results presented here in order to furnish additional experimental explanations.

Molecular and morphological phylogenies concur in indicating that the African lineages formerly referred to Crocodylus niloticus are the sister taxon the four Neotropical crocodiles (Crocodylus intermedius, C. moreleti, C. acutus and C. rhombifer), implying a transoceanic dispersal from Africa to America. So far the fossil record did not contribute to identify a possible African forerunner of the Neotropical species but, curiously, the oldest remains referred to the African C. niloticus are Quaternary in age, whereas the oldest American fossils of Crocodylus are older, being dated to the early Pliocene, suggesting that another species could be involved. We re-described, also thanks to CT imaging, the only well-preserved topotipic skull of Crocodylus checchiai Maccagno, 1947 from the late Miocene (Messinian) African site of As Sahabi in Libya. As previously suggested on the basis of late Miocene material from Tanzania, C. checchiai is a valid, diagnosable species. According to our phylogenetic analyses, C. checchiai is related to the Neotropical taxa and could be even located at the base of their radiation, therefore representing the missing link between the African and the American lineages.

In a previous contribution, a new Riemannian shape space, named TPS space, was introduced to perform statistics on shape data. This space was endowed with a Riemannian metric and a flat connection, with torsion, compatible with the given metric. This connection allows the definition of a Parallel Transport of the deformation compatible with the three-fold decomposition in spherical, deviatoric, and non-affine components. Such a parallel transport also conserves the Γ-energy, strictly related to the total elastic strain energy stored by the body in the original deformation. A new approach is here presented in order to calculate the bending energy on the body alone (body bending energy) and to restrict it exclusively within physical boundaries of objects involved in the deformation analysis. The novelty of this new procedure resides in the fact that we propose a new metric to be preserved during the TPS direct transport. This allows transporting the shape change more coherently with the mechanical meaning of the deformation. The geometry of the TPS space is then further discussed in order to better represent the relationship between the Γ-energy, the strain energy, and the so-called bending energy densities., (© 2019 John Wiley & Sons, Ltd.)

Morphological convergence is an intensely studied macroevolutionary phenomenon. It refers to the morphological resemblance between phylogenetically distant taxa. Currently available methods to explore evolutionary convergence either: rely on the analysis of the phenotypic resemblance between sister clades as compared to their ancestor, fit different evolutionary regimes to different parts of the tree to see whether the same regime explains phenotypic evolution in phylogenetically distant clades, or assess deviations from the congruence between phylogenetic and phenotypic distances. We introduce a new test for morphological convergence working directly with non-ultrametric (i.e. paleontological) as well as ultrametric phylogenies and multivariate data. The method (developed as the function search.conv within the R package RRphylo) tests whether unrelated clades are morphologically more similar to each other than expected by their phylogenetic distance. It additionally permits using known phenotypes as the most recent common ancestors of clades, taking full advantage of fossil information. We assessed the power of search.conv and the incidence of false positives by means of simulations, and then applied it to three well-known and long-discussed cases of (purported) morphological convergence: the evolution of grazing adaptation in the mandible of ungulates with high-crowned molars, the evolution of mandibular shape in sabertooth cats, and the evolution of discrete ecomorphs among anoles of Caribbean islands. The search.conv method was found to be powerful, correctly identifying simulated cases of convergent morphological evolution in 95% of the cases. Type I error rate is as low as 4-6%. We found search.conv is some three orders of magnitude faster than a competing method for testing convergence., Competing Interests: The authors have declared that no competing interests exist.

New Findings: What is the central question of this study? Can impaired deformational indicators for genotype positive for hypertrophic cardiomyopathy in subjects that do not exhibit a left-ventricular wall hypertrophy condition (G+LVH-) be determined using non-invasive 3D echocardiography? What is the main finding and its importance? Using 3D-STE and modern shape analysis, peculiar deformational impairments can be detected in G+LVH- subjects that can be classified with good accuracy. Moreover, the patterns of impairment are located mainly on the apical region in agreement with other evidence coming from previous biomechanical investigations., Abstract: We propose a non-invasive procedure for predicting genotype positive for hypertrophic cardiomyopathy (HCM) in subjects that do not exhibit a left-ventricular wall hypertrophy condition (G+LVH-); the procedure is based on the enhanced analysis of medical imaging from 3D speckle tracking echocardiography (3D-STE). 3D-STE, due to its low quality images, has not been used so far to detect effectively the G+LVH- condition. Here, we post-processed echocardiographic images exploiting the tools of modern shape analysis, and we studied the motion of the left ventricle (LV) during an entire cycle. We enrolled 82 controls, 21 HCM patients and 11 G+LVH- subjects. We followed two steps: (i) we selected the most impaired regions of the LV by analysing its strains; and (ii) we used shape analysis on these regions to classify the subjects. The G+LVH- subjects showed different trajectories and deformational attributes. We found high classification performance in terms of area under the receiver operating characteristic curve (∼90), sensitivity (∼78) and specificity (∼79). Our results showed that (i) G+LVH- subjects present important deformational impairments relative to healthy controls and (ii) modern shape analysis can efficiently predict genotype by means of a non-invasive and inexpensive technique such as 3D-STE., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Background: Understanding the mechanisms promoting or constraining morphological diversification within clades is a central topic in evolutionary biology. Ecological transitions are of particular interest because of their influence upon the selective forces and factors involved in phenotypic evolution. Here we focused on the humerus and mandibles of talpid moles to test whether the transition to the subterranean lifestyle impacted morphological disparity and phenotypic traits covariation between these two structures., Results: Our results indicate non-subterranean species occupy a significantly larger portion of the talpid moles morphospace. However, there is no difference between subterranean and non-subterranean moles in terms of the strength and direction of phenotypic integration., Conclusions: Our study shows that the transition to a subterranean lifestyle significantly reduced morphological variability in talpid moles. However, this reduced disparity was not accompanied by changes in the pattern of traits covariation between the humerus and the mandible, suggesting the presence of strong phylogenetic conservatism within this pattern.

Background: Sparid fishes of the genus Diplodus show a complex life history. Juveniles have adaptations well suited to life in the water column. When fishes recruit into the adult population, individuals develop a radically differentiated shape that reflects their adaptation to the new benthic environment typical of the adult. A comparative analysis of ontogenetic trajectories was performed to assess the presence of divergence in the developmental pattern. By using a geometric morphometric approach, we investigated the pattern of shape variation across ontogenetic stages that span from early settlement to the adult stage in four species of the genus Diplodus. Landmarks were collected on the whole body of fishes to quantify the phenotypic variation along two well defined life stages, i.e. juvenile and adult. A comparative analysis of ontogenetic trajectories was performed to assess the presence of divergence in the developmental pattern. Subsequently, we investigated the patterns of integration and modularity as proxy for the alteration of the developmental processes. This have allowed to give an insight in morphological developmental patterns across ecologically and ontogenetically differentiated life stages and to investigate the process leading to the adult shape., Result: Our results suggest that the origin of morphological novelties in Diplodus spp. arise from shifts of the ontogenetic trajectories during development. During the settlement phase, the juveniles' morphological shapes converge towards similar regions of the morphospace. When the four species approach the transition between settlement and recruitment, we observe the lowest level of inter- and intra-specific disparity. After this transition we detect an abrupt shift of ontogenetic trajectories, i.e. the path taken by species during development, that led to highly divergent adult phenotypes., Discussion: We suggest that the evolution of new ecomorphologies, better suited to exploit different niches (pelagic vs. benthonic) and reduce inter-specific competition in Diplodus spp., are related to the shift in the ontogenetic trajectory that in turn is associated to changes in modularity and integration pattern.

In landmarks-based Shape Analysis size is measured, in most cases, with Centroid Size. Changes in shape are decomposed in affine and non affine components. Furthermore the non affine component can be in turn decomposed in a series of local deformations (partial warps). If the extent of deformation between two shapes is small, the difference between Centroid Size and m-Volume increment is barely appreciable. In medical imaging applied to soft tissues bodies can undergo very large deformations, involving large changes in size. The cardiac example, analyzed in the present paper, shows changes in m-Volume that can reach the 60%. We show here that standard Geometric Morphometrics tools (landmarks, Thin Plate Spline, and related decomposition of the deformation) can be generalized to better describe the very large deformations of biological tissues, without losing a synthetic description. In particular, the classical decomposition of the space tangent to the shape space in affine and non affine components is enriched to include also the change in size, in order to give a complete description of the tangent space to the size-and-shape space. The proposed generalization is formulated by means of a new Riemannian metric describing the change in size as change in m-Volume rather than change in Centroid Size. This leads to a redefinition of some aspects of the Kendall's size-and-shape space without losing Kendall's original formulation. This new formulation is discussed by means of simulated examples using 2D and 3D platonic shapes as well as a real example from clinical 3D echocardiographic data. We demonstrate that our decomposition based approaches discriminate very effectively healthy subjects from patients affected by Hypertrophic Cardiomyopathy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Statistical shape modeling is a powerful tool for visualizing and quantifying geometric and functional patterns of the heart. After myocardial infarction (MI), the left ventricle typically remodels in response to physiological challenges. Several methods have been proposed in the literature to describe statistical shape changes. Which method best characterizes left ventricular remodeling after MI is an open research question. A better descriptor of remodeling is expected to provide a more accurate evaluation of disease status in MI patients. We therefore designed a challenge to test shape characterization in MI given a set of three-dimensional left ventricular surface points. The training set comprised 100 MI patients, and 100 asymptomatic volunteers (AV). The challenge was initiated in 2015 at the Statistical Atlases and Computational Models of the Heart workshop, in conjunction with the MICCAI conference. The training set with labels was provided to participants, who were asked to submit the likelihood of MI from a different (validation) set of 200 cases (100 AV and 100 MI). Sensitivity, specificity, accuracy and area under the receiver operating characteristic curve were used as the outcome measures. The goals of this challenge were to (1) establish a common dataset for evaluating statistical shape modeling algorithms in MI, and (2) test whether statistical shape modeling provides additional information characterizing MI patients over standard clinical measures. Eleven groups with a wide variety of classification and feature extraction approaches participated in this challenge. All methods achieved excellent classification results with accuracy ranges from 0.83 to 0.98. The areas under the receiver operating characteristic curves were all above 0.90. Four methods showed significantly higher performance than standard clinical measures. The dataset and software for evaluation are available from the Cardiac Atlas Project website1.

We aimed at performing a calibration and re-calibration process using six standard risk factors from Northern (NE, N = 2360) or Southern European (SE, N = 2789) middle-aged men of the Seven Countries Study, whose parameters and data were fully known, to establish whether re-calibration gave the right answer. Greenwood-Nam-D'Agostino technique as modified by Demler (GNDD) in 2015 produced chi-squared statistics using 10 deciles of observed/expected CHD mortality risk, corresponding to Hosmer-Lemeshaw chi-squared employed for multiple logistic equations whereby binary data are used. Instead of the number of events, the GNDD test uses survival probabilities of observed and predicted events. The exercise applied, in five different ways, the parameters of the NE-predictive model to SE (and vice-versa) and compared the outcome of the simulated re-calibration with the real data. Good re-calibration could be obtained only when risk factor coefficients were substituted, being similar in magnitude and not significantly different between NE-SE. In all other ways, a good re-calibration could not be obtained. This is enough to praise for an overall need of re-evaluation of most investigations that, without GNDD or another proper technique for statistically assessing the potential differences, concluded that re-calibration is a fair method and might therefore be used, with no specific caution.

The evolutionary relationship between the base and face of the cranium is a major topic of interest in primatology. Such areas of the skull possibly respond to different selective pressures. Yet, they are often said to be tightly integrated. In this paper, we analyzed shape variability in the cranial base and the facial complex in Cercopithecoidea and Hominoidea. We used a landmark-based approach to single out the effects of size (evolutionary allometry), morphological integration, modularity, and phylogeny (under Brownian motion) on skull shape variability. Our results demonstrate that the cranial base and the facial complex exhibit different responses to different factors, which produces a little degree of morphological integration between them. Facial shape variation appears primarily influenced by body size and sexual dimorphism, whereas the cranial base is mostly influenced by functional factors. The different adaptations affecting the two modules suggest they are best studied as separate and independent units, and that-at least when dealing with Catarrhines-caution must be posed with the notion of strong cranial integration that is commonly invoked for the evolution of their skull shape., (© 2017 Wiley Periodicals, Inc.)

We characterized motion attributes arising from LV spatio-temporal analysis of motion distributions in myocardial infarction. Time-varying 3D finite element shape models were obtained in 300 Controls and 300 patients with myocardial infarction. Inter-individual left ventricular shape differences were eliminated using parallel transport to the grand mean of all cases. The first three principal component (PC) scores were used to characterize trajectory attributes. Scores were tested with ANOVA/MANOVA using patient disease status (Infarcts vs. Controls) as a factor. Infarcted patients had significantly different magnitude, orientation and shape of left ventricular trajectories in comparison to Controls. Significant differences were found for the angle between PC scores 1 and 2 in the endocardium, and PC scores 1 and 3 in the epicardium. The largest differences were found in the magnitude of endocardial motion. Endocardial PC scores in shape space showed the highest classification power using support vector machine, with higher total accuracy in comparison to previous methods. Shape space performed better than size-and-shape space for both epicardial and endocardial features. In conclusion, LV spatio-temporal motion attributes accurately characterize the presence of infarction. This approach is easily generalizable to different pathologies, enabling more precise study of the pathophysiological consequences of a wide spectrum of cardiac diseases.

Left ventricle and left atrium are and have been practically always analyzed separately in common clinically and non-clinically oriented cardiovascular investigations. Both classic and speckle tracking echocardiographic data contributed to the knowledge about deformational impairments occurring in systo-diastolic differences. Recently new trajectory based approaches allowed a greater awareness about the entire left ventricle or left atrium revolution and on their deficiencies that take place in presence of hypertrophic cardiomyopathy. However, surprisingly, the concomitant function of the two left heart chambers has not been analyzed for their geometrical/mechanical relationship. For the first time we study here, by acquiring left ventricle and left atrial geometries on the same heartbeat, the trajectory attributes of the entire left heart treated as a whole shape and the shape covariation of its two subunits. We contrasted healthy subjects with patients affected by hypertrophic cardiomyopathy. We found impaired left heart trajectory mainly in terms of orientation and size. More importantly, we found profound differences in the direction of morphological covariation of left ventricle and left atrium. These findings open to new perspectives in pathophysiological evaluation of different diseases by allowing the appreciation of concomitant functioning of both left heart whole geometry and of its two chambers.

Objectives: To study coronary heart disease (CHD) death versus 11 other causes of death using the cumulative incidence function (CIF) and the competing risks procedures to disentangle the differential role of risk factors for different end-points., Material and Methods: Standard Cox and Fine-Gray models among 1712 middle-aged men were compared during 50years of follow-up. CHD death was the primary event, while deaths from 11 selected causes, mutually exclusive from the primary end-point, were considered as secondary events. Reverse solutions were also performed. We considered 10 selected risk factors., Results: CHD death risk was the second highest among 12 mostly specific causes of death. Some risk factors were specific: serum cholesterol for CHD death whereas, systolic blood pressure, cigarette smoking and age may have a differential role in other causes of death. Application of the Fine-Gray model based on CIF enabled to dissect, at least in part, the respective role that baseline covariates may have to segregate the probabilities of two types of death in contrast from each other. They also point to the absence of contributing significance for some of the selected risk factors and this calls for a parsimonious approach in predictions., Conclusions: The relative rarity of competing risk challenges when defining the risk factors role at long-term needs now be corrected since we have clearly shown, with Fine-Gray model, at direct or reverse use, that comparing different end-points heavily influences the risk factor predictive capacity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The analysis of full Left Atrium (LA) deformation and whole LA deformational trajectory in time has been poorly investigated and, to the best of our knowledge, seldom discussed in patients with Hypertrophic Cardiomyopathy. Therefore, we considered 22 patients with Hypertrophic Cardiomyopathy (HCM) and 46 healthy subjects, investigated them by three-dimensional Speckle Tracking Echocardiography, and studied the derived landmark clouds via Geometric Morphometrics with Parallel Transport. Trajectory shape and trajectory size were different in Controls versus HCM and their classification powers had high AUC (Area Under the Receiving Operator Characteristic Curve) and accuracy. The two trajectories were much different at the transition between LA conduit and booster pump functions. Full shape and deformation analyses with trajectory analysis enabled a straightforward perception of pathophysiological consequences of HCM condition on LA functioning. It might be worthwhile to apply these techniques to look for novel pathophysiological approaches that may better define atrio-ventricular interaction.

Objectives: To study coronary heart disease (CHD) incidence versus other cause of death using the cumulative incidence function and the competing risks procedures to disentangle the differential role of risk factors for different end-points., Material and Methods: We compared standard Cox and Fine-Gray models among 1677 middle aged men of an Italian population study of cardiovascular diseases that reached 50years of follow-up with the quasi extinction of the population. The incidence of either fatal or non-fatal cases in 50years was used as primary event, while deaths from any other cause, mutually exclusive from the primary events, were considered as secondary events. We considered 10 selected risk factors., Results: The main result was that cholesterol was significantly and positively related to incidence of CHD contrasted with deaths from any other cause. On the other hand, when the primary events were deaths from any other cause and the competing events were CHD, cholesterol was inversely and age positively related. This outcome did not exclude the predictive role of other risk factors, such as age, cigarettes, arm circumference (protective), systolic blood pressure, vital capacity (protective), cholesterol, corneal arcus and diabetes, documented by the Cox model, that had common roles for both end-points., Conclusions: Fine-Gray model, initially proposed to handle adequately cumulative incidence function may thus prevent overestimation of risks related to the Kaplan-Meier based methods such as Cox model and identify the specific risk factors for defined end-points., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Conventional wisdom holds that the complex shapes of deer antlers are produced under the sole influence of sexual selection. We questioned this view by demonstrating that trends for increased body size evolution passively yield more-complex ornaments, even in organisms where no effect of sexual selection is possible, with similar allometric slopes. Recent investigations suggest that sexual selection on antlers of larger deer species is stronger than that in smaller species; hence, the use of conspicuous antlers for display in large male deer is a secondary function driven by especially intense sexual selection on these large-bodied species. Since ancestral deer were small and had very simple antlers, such an intense selection on antlers shape was probably absent in early deer. Therefore, the evolution of complex ornaments is coupled with body size evolution, even in deer.

Ceratopsidae represents a group of quadrupedal herbivorous dinosaurs that inhabited western North America and eastern Asia during the Late Cretaceous. Although horns and frills of the cranium are highly variable across species, the lower jaw historically has been considered to be relatively conservative in morphology. Here, the lower jaws from 58 specimens representing 21 ceratopsoid taxa were sampled, using geometric morphometrics and 2D finite element analysis (FEA) to explore differences in morphology and mechanical performance across Ceratopsoidea (the clade including Ceratopsidae, Turanoceratops and Zuniceratops). Principal component analyses and non-parametric permuted manovas highlight Triceratopsini as a morphologically distinct clade within the sample. A relatively robust and elongate dentary, a larger and more elongated coronoid process, and a small and dorso-ventrally compressed angular characterize this clade, as well as the absolutely larger size. By contrast, non-triceratopsin chasmosaurines, Centrosaurini and Pachyrhinosaurini have similar morphologies to each other. Zuniceratops and Avaceratops are distinct from other taxa. No differences in size between Pachyrhinosaurini and Centrosaurini are recovered using non-parametric permuted anovas. Structural performance, as evaluated using a 2D FEA, is similar across all groups as measured by overall stress, with the exception of Triceratopsini. Shape, size and stress are phylogenetically constrained. A longer dentary as well as a long coronoid process result in a lower jaw that is reconstructed as relatively much more stressed in triceratopsins., (© 2015 Anatomical Society.)

The enigmatic Early Miocene fossorial mammal Mesoscalops montanensis shows one of the most modified humeri among terrestrial mammals. It has been suggested, on qualitative considerations, that this species has no extant homologues for humerus kinematics and that, functionally, the closest extant group is represented by Chrysochloridae. We combine here three dimensional geometric morphometrics, finite element analysis and phylogenetic comparative methods to explore the shape and mechanical stress states of Mesoscalops montanensis as well as of extant and extinct Talpidae and Chrysochloridae under realistic digging simulations. Evolutionary convergence analyses reveal that the shape of Mesoscalops montanensis represents a unique morphology in the context of fossorial mammals and that its functional performance, albeit superficially similar to that of extant Chrysochloridae, still represents a nonconvergent optimum for adaptation to digging., (© 2015 Wiley Periodicals, Inc.)

Luxuriant, bushy antlers, bizarre crests, and huge, twisting horns and tusks are conventionally understood as products of sexual selection. This view stems from both direct observation and from the empirical finding that the size of these structures grows faster than body size (i.e., ornament size shows positive allometry). We contend that the familiar evolutionary increase in the complexity of ornaments over time in many animal clades is decoupled from ornament size evolution. Increased body size comes with extended growth. Since growth scales to the quarter power of body size, we predicted that ornament complexity should scale according to the quarter power law as well, irrespective of the role of sexual selection in the evolution and function of the ornament. To test this hypothesis, we selected three clades (ammonites, deer, and ceratopsian dinosaurs) whose species bore ornaments that differ in terms of the importance of sexual selection to their evolution. We found that the exponent of the regression of ornament complexity to body size is the same for the three groups and is statistically indistinguishable from 0.25. We suggest that the evolution of ornament complexity is a by-product of Cope's rule. We argue that although sexual selection may control size in most ornaments, it does not influence their shape.

Background: Protoceratops andrewsi (Neoceratopsia, Protoceratopsidae) is a well-known dinosaur from the Upper Cretaceous of Mongolia. Some previous workers hypothesized sexual dimorphism in the cranial shape of this taxon, using qualitative and quantitative observations. In particular, width and height of the frill as well as the development of a nasal horn have been hypothesized as potentially sexually dimorphic., Methodology/principal Findings: Here, we reassess potential sexual dimorphism in skulls of Protoceratops andrewsi by applying two-dimensional geometric morphometrics to 29 skulls in lateral and dorsal views. Principal Component Analyses and nonparametric MANOVAs recover no clear separation between hypothetical "males" and "females" within the overall morphospace. Males and females thus possess similar overall cranial morphologies. No differences in size between "males" and "females" are recovered using nonparametric ANOVAs., Conclusions/significance: Sexual dimorphism within Protoceratops andrewsi is not strongly supported by our results, as previously proposed by several authors. Anatomical traits such as height and width of the frill, and skull size thus may not be sexually dimorphic. Based on PCA for a data set focusing on the rostrum and associated ANOVA results, nasal horn height is the only feature with potential dimorphism. As a whole, most purported dimorphic variation is probably primarily the result of ontogenetic cranial shape changes as well as intraspecific cranial variation independent of sex.

The assessment of left ventricular shape changes during cardiac revolution may be a new step in clinical cardiology to ease early diagnosis and treatment. To quantify these changes, only point registration was adopted and neither Generalized Procrustes Analysis nor Principal Component Analysis were applied as we did previously to study a group of healthy subjects. Here, we extend to patients affected by hypertrophic cardiomyopathy the original approach and preliminarily include genotype positive/phenotype negative individuals to explore the potential that incumbent pathology might also be detected. Using 3D Speckle Tracking Echocardiography, we recorded left ventricular shape of 48 healthy subjects, 24 patients affected by hypertrophic cardiomyopathy and 3 genotype positive/phenotype negative individuals. We then applied Generalized Procrustes Analysis and Principal Component Analysis and inter-individual differences were cleaned by Parallel Transport performed on the tangent space, along the horizontal geodesic, between the per-subject consensuses and the grand mean. Endocardial and epicardial layers were evaluated separately, different from many ecocardiographic applications. Under a common Principal Component Analysis, we then evaluated left ventricle morphological changes (at both layers) explained by first Principal Component scores. Trajectories' shape and orientation were investigated and contrasted. Logistic regression and Receiver Operating Characteristic curves were used to compare these morphometric indicators with traditional 3D Speckle Tracking Echocardiography global parameters. Geometric morphometrics indicators performed better than 3D Speckle Tracking Echocardiography global parameters in recognizing pathology both in systole and diastole. Genotype positive/phenotype negative individuals clustered with patients affected by hypertrophic cardiomyopathy during diastole, suggesting that incumbent pathology may indeed be foreseen by these methods. Left ventricle deformation in patients affected by hypertrophic cardiomyopathy compared to healthy subjects may be assessed by modern shape analysis better than by traditional 3D Speckle Tracking Echocardiography global parameters. Hypertrophic cardiomyopathy pathophysiology was unveiled in a new manner whereby also diastolic phase abnormalities are evident which is more difficult to investigate by traditional ecocardiographic techniques.

We explored the morphological organization of the skull within Crocodylidae, analyzing functional and phylogenetic interactions between its 2 constituent functional modules: the rostrum and the postrostrum. We used geometric morphometrics to identify localized shape changes, focusing on the differences between the major clades of the crown-group Crocodylia: Alligatoridae and Crocodylidae. We used published bite performance data to correlate rostral function with postrostral morphology. The skull modules appear more integrated within Alligatoridae than within Crocodyliade. Phylogenetic effects on shape variation are more evident in Alligatoridae than in Crocodylidae, where functional parameters concerning the rostral morphology are proportionally more important than phylogeny. Long-snouted species are characterized by low structural performance, which is significantly associated with a reduction of the pterygoid-quadrate cranial nipper, suggesting that the nipper is important for the ingestion of large food items in generalist species. This functional association is coupled with a significant evolutionary allometry at the clade level, while Alligatoridae and Crocodylidae show different degrees of evolutionary allometry for their entire shape and rostrum. The postrostrum is more conservative than the rostrum in terms of morphospace occupation, evolutionary allometry and phylogenetic signal., (© 2013 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.)

The aim of this study is to investigate human left ventricular heart morphological changes in time among 17 healthy subjects. Preliminarily, 2 patients with volumetric overload due to aortic insufficiency were added to our analyses. We propose a special strategy to compare the shape, orientation and size of cardiac cycle's morphological trajectories in time. We used 3D data obtained by Speckle Tracking Echocardiography in order to detect semi-automated and homologous landmarks clouds as proxies of left ventricular heart morphology. An extended Geometric Morphometrics toolkit in order to distinguish between intra- and inter-individual shape variations was used. Shape of trajectories with inter-individual variation were compared under the assumption that trajectories attributes, estimated at electrophysiologically homologous times are expressions of left ventricular heart function. We found that shape analysis as commonly applied in Geometric Morphometrics studies fails in identifying a proper morpho-space to compare the shape of morphological trajectories in time. To overcome this problem, we performed a special type of Riemannian Parallel Transport, called "linear shift". Whereas the two patients with aortic insufficiency were not differentiated in the static shape analysis from the healthy subjects, they set apart significantly in the analyses of motion trajectory's shape and orientation. We found that in healthy subjects, the variations due to inter-individual morphological differences were not related to shape and orientation of morphological trajectories. Principal Component Analysis showed that volumetric contraction, torsion and twist are differently distributed on different axes. Moreover, global shape change appeared to be more correlated with endocardial shape change than with the epicardial one. Finally, the total shape variation occurring among different subjects was significantly larger than that observable across properly defined morphological trajectories.

Background: Recent assessments of morphological changes in the frill during ontogeny hypothesized that the late Maastrichtian horned dinosaur Torosaurus represents the "old adult" of Triceratops, although acceptance of this finding has been disputed on several lines of evidence., Methodology/principal Findings: Examining the cranial morphology of 28 skulls in lateral view and 36 squamosals of Nedoceratops hatcheri, Triceratops spp. and Torosaurus spp. by means of landmark-based geometric morphometrics, we compared ontogenetic trajectories among these taxa. Principal Component Analysis and cluster analysis confirmed different cranial morphologies. Torosaurus shape space is well separated from Triceratops, whereas Triceratops horridus and Triceratops prorsus partially overlap within Triceratops shape space. Linear regressions between shape and size suggest different ontogenetic trajectories among these taxa. Results support the "traditional" taxonomic status of Torosaurus. We hypothesize that ontogeny drives cranial morphology with different patterns between Torosaurus and Triceratops., Conclusions/significance: Torosaurus is a distinct and valid taxon. Whether looking at entire skulls, skulls without the frill, frills alone, or squamosals, Torosaurus has different morphologies and distinct allometric trajectories compared to Triceratops. This new approach confirms the taxonomic status of Torosaurus as well as the comparatively low diversity of ceratopsids at the end of the Maastrichtian in North America.

Cat-like carnivorous mammals represent a relatively homogeneous group of species whose morphology appears constrained by exclusive adaptations for meat eating. We present the most comprehensive data set of extant and extinct cat-like species to test for evolutionary transformations in size, shape and mechanical performance, that is, von Mises stress and surface traction, of the mandible. Size and shape were both quantified by means of geometric morphometrics, whereas mechanical performance was assessed applying finite element models to 2D geometry of the mandible. Additionally, we present the first almost complete composite phylogeny of cat-like carnivorans for which well-preserved mandibles are known, including representatives of 35 extant and 59 extinct species of Felidae, Nimravidae, and Barbourofelidae. This phylogeny was used to test morphological differentiation, allometry, and covariation of mandible parts within and among clades. After taking phylogeny into account, we found that both allometry and mechanical variables exhibit a significant impact on mandible shape. We also tested whether mechanical performance was linked to morphological integration. Mechanical stress at the coronoid process is higher in sabertoothed cats than in any other clade. This is strongly related to the high degree of covariation within modules of sabertooths mandibles. We found significant correlation between integration at the clade level and per-clade averaged stress values, on both original data and by partialling out interclade allometry from shapes when calculating integration. This suggests a strong interaction between natural selection and the evolution of developmental and functional modules at the clade level.

The phylogenetic placement of Tomistoma and Gavialis crocodiles depends largely upon whether molecular or morphological data are utilized. Molecular analyses consider them as sister taxa, whereas morphological/paleontological analyses set Gavialis apart from Tomistoma and other crocodylian species. Here skull allometric trajectories of Tomistoma and Gavialis were contrasted with those of two longirostral crocodylian taxa, Crocodylus acutus and Mecistops cataphractus, to examine similarities in growth trajectories in light of this phylogenetic controversy. Entire skull shape and its two main modules, rostrum and postrostrum, were analyzed separately. We tested differences for both multivariate angles between trajectories and for shape differences at early and late stages of development. Based on a multivariate regression of shape data and size, Tomistoma seems to possess a peculiar rate of growth in comparison to the remaining taxa. However, its morphology at both juvenile and adult sizes is always closer to those of Brevirostres crocodylians, for the entire head shape, as well as the shape of the postrostrum and rostrum. By contrast, the allometric trajectory of Gavialis always begins and ends in a unique region of the multidimensional morphospace. These findings concur with a morphological hypothesis that places Gavialis separate from Brevirostres, and Tomistoma closer to other crocodylids, and provides an additional, and independent, data set to inform on this ongoing phylogenetic discussion., (© 2010 Wiley Periodicals, Inc.)

Mandibles and teeth of ungulates have been extensively studied to discern the functional significance of their design. Grazing ungulates have deeper mandibles, longer coronoid processes, flatter incisor arcades, and more hypsodont molars in comparison to browsers. If the functional significance of both mandible and teeth shapes is well-established, it remains uncertain to what extent mandible shapes are really adapted to grazing, meaning that they evolved either to serve their current biological function or just as a structural requirement to accommodate higher crowned molars. Here, we address this question by studying the contribution of phylogeny, hypsodonty, and body size to mandibular shape variation. The mandible shape appeared to be significantly influenced by hypsodonty but not by body size. Interestingly, hypsodonty-related changes influenced the tooth row in artiodactyls and perissodactyls significantly but in the opposite directions, which is ultimately related to their different digestive strategies. Yet, we obtained a strong phylogenetic effect in perissodactyls, suggesting that their mandible shape should be strongly inherited. The strength of this effect was not significant within artiodactyls (where hypsodonty explained much more variance in mandible shape). Digestive strategy is deemed to interplay with hypsodonty to produce different paths of adaptation to particular diets in ungulates.