Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies.

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized using GCN-Explainer, an ablation study and univariate t-testing. The results showed a mean classification accuracy of 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Sex classification accuracy was substantially better across datasets (73-81%). Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes. These results suggest that whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity as further supported by the higher accuracy for sex classification using the same methods. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.

Neural suppression in odor recognition memory.

Little is known about the neural basis of lower- and higher-order olfactory functions such as odor memory, compared with other sensory systems. The aim of this study was to explore neural networks and correlates associated with 3 functions: passive smelling (PS), odor encoding (OE), and in particular odor recognition memory (ORM). Twenty-six healthy participants were examined using functional magnetic resonance imaging conducted across 3 sessions, one for each function. Independent component analysis revealed a difference between sessions where a distinct ORM component incorporating hippocampus and posterior cingulate showed delayed triggering dissociated from odor stimulation and recognition. By contrasting Hit for ORM (target odors correctly recognized as old) and a combination of PS and detected odors from OE, we found significantly lower activations in amygdala, piriform cortex, insula, thalamus, and the inferior parietal lobule. Region of interest analysis including anterior insula, posterior cingulate gyrus, dentate gyrus, left middle frontal gyrus, amygdala, and piriform cortex demonstrated that Hit were associated with lower activations compared with other memory responses. In summary, our findings suggest that successful recognition of familiar odors (odor familiarity) is associated with neural suppression in the abovementioned regions of interest. Additionally, network including the hippocampus and posterior cingulate is engaged in a postrecognition process. This process may be related to incidental encoding of less familiar and more novel odors (odor novelty) and should be subject for future research.

Preoperative Expectations Versus Reality: A Patient Experience Study Following Scarf Osteotomy for Hallux Valgus Correction.

The relationship between managing patient expectations and postoperative functional outcomes has been studied widely in other areas of orthopedics, but there is a paucity of information in the foot and ankle literature. The primary objective of the study was to identify the most common patient "expectations" from hallux valgus surgery and establish over what time period postsurgery they would meet those goals. A prospective study of 45 consecutive patients was performed at a single center. This included adult patients (>18 years old) that underwent a scarf osteotomy for primary hallux valgus correction. Patients were followed up for 6 months and completed pre- and postoperative Manchester-Oxford Foot Questionnaire and Visual Analogue Scale scores. A separate "expectations" questionnaire was designed and completed assessing the patient's preoperative rehabilitation expectations compared to the actual time taken to achieve those goals. These included 5 domains: pain improvement, return to walking unaided, return to normal foot sensation, return to normal footwear, and return to driving. The postoperative functional scores demonstrated statistically significant improvement postsurgery (p < .001). It also highlighted the overall time frame over which the above expectations were met. On average, patients achieved satisfactory pain improvements 1.4 weeks earlier than expected (p < .001) along with trends toward an earlier return to driving function of patient expectation (p < .05). Patients can thus be reliably informed that their pain symptoms are likely to settle within one month of surgery. This should allow patients to prepare for their rehabilitation more informed, thus facilitating earlier weightbearing and return to function.

Caspases from scleractinian coral show unique regulatory features.

Coral reefs are experiencing precipitous declines around the globe with coral diseases and temperature-induced bleaching being primary drivers of these declines. Regulation of apoptotic cell death is an important component in the coral stress response. Although cnidaria are known to contain complex apoptotic signaling pathways, similar to those in vertebrates, the mechanisms leading to cell death are largely unexplored. We identified and characterized two caspases each from Orbicella faveolata, a disease-sensitive reef-building coral, and Porites astreoides, a disease-resistant reef-building coral. The caspases are predicted homologs of the human executioner caspases-3 and -7, but OfCasp3a (Orbicella faveolata caspase-3a) and PaCasp7a (Porites astreoides caspase-7a), which we show to be DXXDases, contain an N-terminal caspase activation/recruitment domain (CARD) similar to human initiator/inflammatory caspases. OfCasp3b (Orbicella faveolata caspase-3b) and PaCasp3 (Porites astreoides caspase-3), which we show to be VXXDases, have short pro-domains, like human executioner caspases. Our biochemical analyses suggest a mechanism in coral which differs from that of humans, where the CARD-containing DXXDase is activated on death platforms but the protease does not directly activate the VXXDase. The first X-ray crystal structure of a coral caspase, of PaCasp7a determined at 1.57 Å resolution, reveals a conserved fold and an N-terminal peptide bound near the active site that may serve as a regulatory exosite. The binding pocket has been observed in initiator caspases of other species. These results suggest mechanisms for the evolution of substrate selection while maintaining common activation mechanisms of CARD-mediated dimerization.

Resurrection of ancestral effector caspases identifies novel networks for evolution of substrate specificity.

Apoptotic caspases evolved with metazoans more than 950 million years ago (MYA), and a series of gene duplications resulted in two subfamilies consisting of initiator and effector caspases. The effector caspase genes (caspases-3, -6, and -7) were subsequently fixed into the Chordata phylum more than 650 MYA when the gene for a common ancestor (CA) duplicated, and the three effector caspases have persisted throughout mammalian evolution. All caspases prefer an aspartate residue at the P1 position of substrates, so each caspase evolved discrete cellular roles through changes in substrate recognition at the P4 position combined with allosteric regulation. We examined the evolution of substrate specificity in caspase-6, which prefers valine at the P4 residue, compared with caspases-3 and -7, which prefer aspartate, by reconstructing the CA of effector caspases (AncCP-Ef1) and the CA of caspase-6 (AncCP-6An). We show that AncCP-Ef1 is a promiscuous enzyme with little distinction between Asp, Val, or Leu at P4. The specificity of caspase-6 was defined early in its evolution, where AncCP-6An demonstrates a preference for Val over Asp at P4. Structures of AncCP-Ef1 and of AncCP-6An show a network of charged amino acids near the S4 pocket that, when combined with repositioning a flexible active site loop, resulted in a more hydrophobic binding pocket in AncCP-6An. The ancestral protein reconstructions show that the caspase-hemoglobinase fold has been conserved for over 650 million years and that only three substitutions in the scaffold are necessary to shift substrate selection toward Val over Asp.

The role of sensory innervation in cornea-lens regeneration.

BACKGROUND: Numerous sensory nerves in the cornea contribute to normal tissue homeostasis. Interestingly, cells within the basal corneal epithelium can regenerate new lenses in the frog, Xenopus. In this study, we investigated whether cornea sensory nerves or their neuropeptides are important for supporting cornea-lens regeneration. RESULTS: Attempts to sever the trigeminal nerve trunk, which provides sensory nerve branches to the cornea, did not inhibit lens regeneration. However, using this approach we found that it was not possible to completely disrupt sensory innervation, as these nerves are able to quickly regenerate back to the cornea. On the other hand, attenuation of neuropeptide levels with capsaicin was found to significantly inhibit lens regeneration, as visualized by a reduction of Substance P. These treatments also led to a reduction of cornea sensory innervation. Interestingly, inhibition of the Substance P-preferred receptor NK-1 with Spantide II did not affect lens-regeneration rates. CONCLUSIONS: This study provides evidence that cornea nerves support cornea-lens regeneration, which could occur through the release of various neurotrophic factors. Substance P, however, does not appear to be the critical component of this signaling pathway. Further studies are needed to investigate what role other known neurotrophic factors may play in this process.

Diverse Evolutionary Origins and Mechanisms of Lens Regeneration.

In this review, we compare and contrast the three different forms of vertebrate lens regeneration: Wolffian lens regeneration, cornea-lens regeneration, and lens regeneration from lens epithelial cells. An examination of the diverse cellular origins of these lenses, their unique phylogenetic distribution, and the underlying molecular mechanisms, suggests that these different forms of lens regeneration evolved independently and utilize neither conserved nor convergent mechanisms to regulate these processes.

Efficient Adiabatic Spin-Dependent Kicks in an Atom Interferometer.

We present an atom interferometry technique in which the beam splitter is split into two separate operations. A microwave pulse first creates a spin-state superposition, before optical adiabatic passage spatially separates the arms of that superposition. Despite using a thermal atom sample in a small (600 µm) interferometry beam, this procedure delivers an efficiency of 99% per ℏk of momentum separation. Utilizing this efficiency, we first demonstrate interferometry with up to 16ℏk momentum splitting and free-fall limited interrogation times. We then realize a single-source gradiometer, in which two interferometers measuring a relative phase originate from the same atomic wave function. Finally, we demonstrate a resonant interferometer with over 100 adiabatic passages, and thus over 400ℏk total momentum transferred.

Morphological, physiological and molecular responses of Nitzschia palea under cadmium stress.

The impact of cadmium on the diatom Nitzschia palea (Kützing) W. Smith 1856 was studied by examining the relation between valve deformities and response through biological processes and genetic expression. Cultures of N. palea were exposed to two Cd treatments (C1 = 2.4 ± 0.6 and C2 = 42.6 ± 4.2 µg Cd/L) along with a control (C0 = 0 µg Cd/L) for 28 days. Cadmium bioaccumulation, diatoms growth, photosynthetic efficiencies, valve deformities and genetic expression were investigated during the course of the experiment. Cadmium exposure had significant effects on bioaccumulation, growth, valve deformities and genetic expression. Maximal effects for all studied endpoints were recorded after 7 days of exposure for the C2 treatment, which corresponded to the sampling time and condition with maximum cadmium bioaccumulation. Abnormal raphe formations (deviation from its lateral position) were significantly more abundant in the C2 treatment compared to the control. Molecular responses were related to cadmium level based on the number of genes impacted, intensity of the response and the frequency of observations. The expression of genes involved in the regulation of mitochondrial metabolism, photosynthesis, oxidative stress and silica metabolism was affected by cadmium exposure.

A Republican Argument Against Nudging and Informed Consent.

I argue that it is impermissible to use nudges as a tool to influence patients in the context of informed consent. The motivation for such nudges is that their use can help reconcile potential conflicts between a physician's duty of beneficence and duty to respect patient autonomy. I argue that their use places physicians in a position of domination over patients. That is, it violates the republican freedom of patients because it grants physicians the power to arbitrarily interfere. I also argue that if one tries to adjust the duty of beneficence to avoid this conclusion, then the republican freedom of patients is still threatened under conditions of clinical equipoise. As ways to avoid the inevitability of nudging, I suggest the alternative of boosting or the pairing of patients with physicians who share their deep values. This latter option achieves the benefits nudging patients is supposed to provide without violating the republican freedom of those patients.

Preparation and Characterization of Biomimetic ß-Lens Crystallins Using Single-Chain Polymeric Nanoparticles.

Presbyopia, the inability to focus at arm's length, and cataracts that cloud vision are associated primarily with changes in the mechanical and optical properties of the lens. The optical properties, particularly the refractive index, of the human lens originate from the cytoplasm of the lens fiber, which contains a highly concentrated solution (∼40%) of globular proteins referred to as α, ß, and γ crystallins, of which ß is the most abundant. In this study, we focus on the synthesis and characterization of a ß-crystallin biomimetic in an effort to understand and develop treatments for presbyopia and cataract. Polyacrylamide was used as a protein analogue. The side chains were endowed with aromatic and acidic functionality. Acrylic acid was incorporated into the copolymer and cross-linked with diamines to form nanoparticles. The composition and cross-linking condition of the biomimetic copolymers were optimized to match the hydrodynamic radius (Rh), refractive index, size, density, and intrinsic and dynamic viscosities with those of ßhigh lens crystallins. The refractive indices and densities of the nanoparticles' dispersion at different concentrations matched that of ßhigh lens crystallins, and the viscosity of the nanoparticles approached that of ßhigh lens crystallins. The biocompatibility findings for primary porcine retinal pigment epithelial (ppRPE) cells and porcine lens epithelial (pLE) cells showed both cell types tolerated up to 30 mg/mL of nanoparticles. These materials have the potential for use as replacements for the crystallins in developing an accommodating intraocular lens nanocomposite hydrogel that closely replicates the natural autofocusing ability of the original.

A comparison of molecular markers and morphology for Neidium taxa (Bacillariophyta) from eastern North America.

Historically, a morphological species concept has applied shape subjectively in the delimitation of diatom species. This has led to confusion between taxa within the benthic diatom genus Neidium. Samples from Ontario, Quebec, Nova Scotia, Newfoundland (Canada) and New York (USA) were examined for Neidium taxa under LM and SEM. Fourier shape analysis showed that shape as a taxonomic character was not able to discern all species. Isolated individuals from the samples were amplified and sequenced for three chloroplast molecular markers (rbcL, psbC, and psbA) and one nuclear ribosomal molecular marker (18S). Phylogenetic reconstructions were completed with the concatenated chloroplast and 18S dataset using Maximum Likelihood and Bayesian analyses. The concatenated chloroplast dataset exhibited a species-level resolution phylogeny of Neidium taxa. The 18S dataset had a lower level of sequence divergence and was unable to differentiate between Neidium taxa. We present emended species descriptions and sequence data for four previously described species: Neidium sacoense, N. longiceps, N. fossum, and N. affine. We describe three novel species (Neidium lowei, N. promontorium, and N. potapovae) and identify two forms with unique molecular signatures. The distinguishing features of N. lowei are its size, valve shape, and longitudinal canal structure. Distinguishing features of N. promontorium are its valve shape, longitudinal canal and apex formation, and surface depression along the axial area. Neidium potapovae is distinguished by its size, formation of valve and apices and single longitudinal canal. This paper demonstrates how future phylogenetic treatments using single cell multigene sequencing can help resolve taxonomic confusion within diatoms.

Effects of Long-Term Anthropogenic Disturbance on the Benthic Episammic Diatom Community of an Ancient, Tropical Lake.

Habitat homogenization, nutrient enrichment and loss of biodiversity are broadly recognized as the consequences of human activity in aquatic systems. Diatoms (Bacillariophyceae) are frequently used in aquatic environmental assessment and impact monitoring, but in unique habitats dominated by endemic taxa, traditional approaches may not be appropriate. We examined the impacts of long term anthropogenic impacts upon the littoral episammic diatom community around the town of Soroako, located on Lake Matano, an ancient tropical lake. Lake Matano is located on central Sulawesi Island, Indonesia, and socio-economic conditions are typical of developing nations. Although differences in nutrient concentrations were undetectable with field-based spectroscopy approaches, mean Shannon diversity was decreased in association with proximity the town-site. However, mean ß-diversity was maintained despite several decades of shoreline modification at Soroako. Elevated abundances of early-successional diatom taxa in the disturbed area drove differences between areas immediately offshore of Soroako and those farther away. These findings suggest that increased physical disturbance and TSS loads around Soroako, rather than increased nutrient loading, influenced shifts in the diatom community. These results suggest that microscopy-based biomonitoring approaches are sensitive indicators of environmental modification that could be useful in areas where access to cutting-edge analytical equipment is limited.

Olfactory modulation of affective touch processing - A neurophysiological investigation.

Touch can be highly emotional, and depending on the environment, it can be perceived as pleasant and comforting or disgusting and dangerous. Here, we studied the impact of context on the processing of tactile stimuli using a functional magnetic resonance imaging (fMRI) paradigm. This was achieved by embedding tactile stimulation in a variable olfactory environment. Twenty people were scanned with BOLD fMRI while receiving the following stimulus blocks: Slow stroking Touch, Civette odor (feces like), Rose odor, Touch+Civette, and Touch+Rose. Ratings of pleasantness and intensity of tactile stimuli and ratings of disgust and intensity of olfactory stimuli were collected. The impact of the olfactory context on the processing of touch was studied using covariance analyses. Coupling between olfactory processing and somatosensory processing areas was assessed with psychophysiological interaction analysis (PPI). A subjectively disgusting olfactory environment significantly reduced the perceived pleasantness of touch. The touch fMRI activation in the secondary somatosensory cortex, operculum 1 (OP1), was positively correlated with the disgust towards the odors. Decreased pleasantness of touch was related to decreased posterior insula activity. PPI analysis revealed a significant interaction between the OP1, posterior insula, and regions processing the disgust of odors (orbitofrontal cortex and amygdala). We conclude that the disgust evaluation of the olfactory environment moderates neural reactivity in somatosensory regions by upregulation of the OP1 and downregulation of the posterior insula. This adaptive regulation of affective touch processing may facilitate adaptive reaction to a potentially harmful stimulus.

Temporal dynamics of brain activation during 40 minutes of pleasant touch.

INTRODUCTION: Touch is important for individuals' subjective well-being, is typically rewarding, and is one of few sensory stimuli which are experienced as pleasant for a rather long time. This study tracked brain activation during slow stroking stimulation of the arm that was applied continuously for 40min - a much longer time than what previous studies have investigated. METHODS: 25 subjects were stroked for 40min with a soft brush while they were scanned with functional Magnetic Resonance Imaging, and rated the perceived pleasantness of the brush stroking. Two resting baselines were included. Whole brain-based analyses investigated the neural response to long-lasting stroking. RESULTS: Stroking was perceived as pleasant throughout scanning and activated areas that were previously found to be involved in the processing of pleasant touch. Activation in primary somatosensory cortex (S1) and S2, subdivision OP1, decreased over time, whereas activation in orbito-frontal gyrus (OFC) and putamen strongly increased until reaching a plateau after approximately 20min. Similarly, functional connectivity of posterior insula with middle cingulate and striatal regions increased over time. DISCUSSION: Long-lasting stroking was processed in similar areas as shorter-lasting stroking. The decreased activation in somatosensory cortices over time may represent stimulus habituation, whereas increased activation in OFC and putamen may relate to the stimulation's subjective reward value. This involvement of reward-related brain circuits can facilitate maintenance of long-lasting social touch interactions.

The lens regenerative competency of limbal vs. central regions of mature Xenopus cornea epithelium.

The frog, Xenopus laevis, is capable of completely regenerating a lens from the cornea epithelium. Because this ability appears to be limited to the larval stages of Xenopus, virtually all the work to understand the mechanisms regulating this process has been limited to pre-metamorphic tadpoles. It has been reported that the post-metamorphic cornea is competent to regenerate under experimental conditions, despite the fact that the in vivo capacity to regenerate is lost; however, that work didn't examine the regenerative potential of different regions of the cornea. A new model suggests that cornea-lens regeneration in Xenopus may be driven by oligopotent stem cells, and not by transdifferentiation of mature cornea cells. We investigated the regenerative potential of the limbal region in post-metamorphic cornea, where the stem cells of the cornea are thought to reside. Using EdU (5-Ethynyl-2'-deoxyuridine), we identified long-term label retaining cells in the basal cells of peripheral post-metamorphic Xenopus cornea, consistent with slow-cycling stem cells of the limbus that have been described in other vertebrates. Using this data to identify putative stem cells of the limbal region in Xenopus, we tested the regenerative competency of limbal regions and central cornea. These regions showed a similarly high ability for the cells of the basal epithelium to express lens proteins when cultured in proximity to larval retina. Thus, the regenerative competency in the post-metamorphic cornea is not restricted to stem cells of the limbal region, but also occurs in the transit amplifying cells throughout the basal layer of the cornea epithelium.

Lens regeneration from the cornea requires suppression of Wnt/ß-catenin signaling.

The frog, Xenopus laevis, possesses a high capacity to regenerate various larval tissues, including the lens, which is capable of complete regeneration from the cornea epithelium. However, the molecular signaling mechanisms of cornea-lens regeneration are not fully understood. Previous work has implicated the involvement of the Wnt signaling pathway, but molecular studies have been very limited. Iris-derived lens regeneration in the newt (Wolffian lens regeneration) has shown a necessity for active Wnt signaling in order to regenerate a new lens. Here we provide evidence that the Wnt signaling pathway plays a different role in the context of cornea-lens regeneration in Xenopus. We examined the expression of frizzled receptors and wnt ligands in the frog cornea epithelium. Numerous frizzled receptors (fzd1, fzd2, fzd3, fzd4, fzd6, fzd7, fzd8, and fzd10) and wnt ligands (wnt2b.a, wnt3a, wnt4, wnt5a, wnt5b, wnt6, wnt7b, wnt10a, wnt11, and wnt11b) are expressed in the cornea epithelium, demonstrating that this tissue is transcribing many of the ligands and receptors of the Wnt signaling pathway. When compared to flank epithelium, which is lens regeneration incompetent, only wnt11 and wnt11b are different (present only in the cornea epithelium), identifying them as potential regulators of cornea-lens regeneration. To detect changes in canonical Wnt/ß-catenin signaling occurring within the cornea epithelium, axin2 expression was measured over the course of regeneration. axin2 is a well-established reporter of active Wnt/ß-catenin signaling, and its expression shows a significant decrease at 24 h post-lentectomy. This decrease recovers to normal endogenous levels by 48 h. To test whether this signaling decrease was necessary for lens regeneration to occur, regenerating eyes were treated with either 6-bromoindirubin-3'-oxime (BIO) or 1-azakenpaullone - both activators of Wnt signaling - resulting in a significant reduction in the percentage of cases with successful regeneration. In contrast, inhibition of Wnt signaling using either the small molecule IWR-1, treatment with recombinant human Dickkopf-1 (rhDKK1) protein, or transgenic expression of Xenopus DKK1, did not significantly affect the percentage of successful regeneration. Together, these results suggest a model where Wnt/ß-catenin signaling is active in the cornea epithelium and needs to be suppressed during early lens regeneration in order for these cornea cells to give rise to a new lentoid. While this finding differs from what has been described in the newt, it closely resembles the role of Wnt signaling during the initial formation of the lens placode from the surface ectoderm during early embryogenesis.

Atom interferometry in an optical cavity.

We propose and demonstrate a new scheme for atom interferometry, using light pulses inside an optical cavity as matter wave beam splitters. The cavity provides power enhancement, spatial filtering, and a precise beam geometry, enabling new techniques such as low power beam splitters (<100 µW), large momentum transfer beam splitters with modest power, or new self-aligned interferometer geometries utilizing the transverse modes of the optical cavity. As a first demonstration, we obtain Ramsey-Raman fringes with >75% contrast and measure the acceleration due to gravity, g, to 60 µg/sqrt[Hz] resolution in a Mach-Zehnder geometry. We use >10(7) cesium atoms in the compact mode volume (600 µm 1/e(2) waist) of the cavity and show trapping of atoms in higher transverse modes. This work paves the way toward compact, high sensitivity, multiaxis interferometry.

Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients.

BACKGROUND: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification. METHODS: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg). Mean wavelet entropy was derived from flow-velocity data and compared with traditional haemodynamic measures of microvascular function, namely the resistive and pulsatility indices. RESULTS: Entropy, was significantly higher in control participants in the central retinal artery (CRA) (differential mean 0.11 (standard error 0.05 cms(-1)), CI 0.009 to 0.219, p 0.017) and ophthalmic artery (0.12 (0.05), CI 0.004 to 0.215, p 0.04). In comparison, the resistive index (0.12 (0.05), CI 0.005 to 0.226, p 0.029) and pulsatility index (0.96 (0.38), CI 0.19 to 1.72, p 0.015) showed significant differences between groups in the CRA alone. Regression analysis indicated that entropy was significantly influenced by age and systolic blood pressure (r values 0.4-0.6). None of the measures were significantly altered in the larger conduit vessel. CONCLUSION: This is the first application of entropy to human blood velocity waveform analysis and shows that this new technique has the ability to discriminate health from early hypertensive disease, thereby promoting the early identification of cardiovascular disease in a young hypertensive population. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov, NCT01047423.