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INTRODUCTION: Amnestic mild cognitive impairment (aMCI) is emerging as a heterogeneous condition. METHODS: We looked at a cohort of N = 207 aMCI subjects, with baseline fluorodeoxyglucose positron emission tomography (FDG‐PET), T1 magnetic resonance imaging, cerebrospinal fluid (CSF), apolipoprotein E (APOE), and neuropsychological assessment. An algorithm based on FDG‐PET hypometabolism classified each subject into subtypes, then compared biomarker measures and clinical progression. RESULTS: Three subtypes emerged: hippocampal sparing–cortical hypometabolism, associated with younger age and the highest level of Alzheimer's disease (AD)‐CSF pathology; hippocampal/cortical hypometabolism, associated with a high percentage of APOE ε3/ε4 or ε4/ε4 carriers; medial–temporal hypometabolism, characterized by older age, the lowest AD‐CSF pathology, the most severe hippocampal atrophy, and a benign course. Within the whole cohort, the severity of temporo‐parietal hypometabolism, correlated with AD‐CSF pathology and marked the rate of progression of cognitive decline. DISCUSSION: FDG‐PET can distinguish clinically comparable aMCI at single‐subject level with different risk of progression to AD dementia or stability. The obtained results can be useful for the optimization of pharmacological trials and automated‐classification models. Highlights: Algorithm based on FDG‐PET hypometabolism demonstrates distinct subtypes across aMCI;Three different subtypes show heterogeneous biological profiles and risk of progression;The cortical hypometabolism is associated with AD pathology and cognitive decline;MTL hypometabolism is associated with the lowest conversion rate and CSF‐AD pathology. [ABSTRACT FROM AUTHOR]

Summary: One‐dimensional models for river bifurcations rely on a nodal point relation that determines the distribution of sediments between the downstream branches. The most widely‐adopted nodal point relation describes the two‐dimensional topographic effects exerted by the bifurcation by introducing two computational cells, located just upstream the bifurcation node, that laterally exchange water and sediments. The results of this approach strongly depend on a dimensionless parameter that represents the ratio between the cell length and the main channel width, whose value needs to be empirically estimated. Previous works proposed calibrating this parameter on the basis of more complete two‐dimensional linear models, which directly solve the momentum and mass conservation equations. This study demonstrates that a full consistency between the one‐dimensional approach and the two‐dimensional models can be directly achieved by adopting different scaling for the bifurcation cell length, which results in a theoretically‐defined and constant dimensionless length parameter. Comparison with experimental observations reveals that this physically‐based scaling yields more accurate predictions of bifurcation stability and discharge asymmetry. This indicates that the proposed method may provide a more reliable and precise estimation of the cell length, potentially improving the performance of one‐dimensional models for bifurcation processes in rivers. [ABSTRACT FROM AUTHOR]

Engineered grafts constitute an alternative to autologous transplant for repairing severe peripheral nerve injuries. However, current clinically available solutions have substantial limitations and are not suited for the repair of long nerve defects. A novel design of nerve conduit is presented here, which consists of a chitosan porous matrix embedding a 3D‐printed poly‐ε‐caprolactone mesh. These materials are selected due to their high biocompatibility, safe degradability, and ability to support the nerve regeneration process. The proposed design allows high control over geometrical features, pores morphology, compression resistance, and bending stiffness, yielding tunable and easy‐to‐manipulate grafts. The conduits are tested in chronic animal experiments, aiming to repair a 15‐mm long gap in the sciatic nerve of rats, and the results are compared with an autograft. Electrophysiological and nociception tests performed monthly during a 4‐month follow‐up show that these conduits allow a good degree of muscle functional recovery. Histological analyses show abundant cellularization in the wall and in the lumen of the conduits and regenerated axons within all rats treated with these grafts. It is suggested that the proposed conduits have the potential to repair nerves over the limiting gap length and can be proposed as strategy to overcome the limitations of autograft. [ABSTRACT FROM AUTHOR]

A simple experimental method to estimate the power effectively absorbed by a plasma is presented. It relies on a thermal management study that is applied to the whole discharge system, providing the energy released by the plasma and lost by convection and radiation at the reactor walls. The methodology is illustrated in the case of H2 Electron Cyclotron Resonance microwave plasma. Nevertheless, this method can be extended to a variety of electrical discharge or feed gases. Using this method, an experimental coupling efficiency of ∼22 ± ∼8% was derived. In comparison, an analytical balance of the plasma power absorption yields a theoretical coupling efficiency of ∼28 ± ∼9%. [ABSTRACT FROM AUTHOR]

A striking feature of rivers is their ability to sort the sediments composing them. One of the chief causes for grain sorting consists in the selective transport of different sizes moving downstream. This process can be substantially influenced by the presence of lateral topographic variations, as those produced by channel bifurcations, in which water and sediment are diverted between two smaller anabranches. In particular, field and laboratory observations have shown that the asymmetric flux distribution commonly observed in actual bifurcations is associated with a coarsening of the most‐carrying branch. Here, equilibrium sorting in river bifurcations is addressed through a quasi‐2D model. Differently from previous works, a fully physically based description of the processes tied to a heterogeneous sediment mixture is introduced. The main mechanisms consist in the lateral pull of sediment due to a sloping bed upstream the bifurcation, and the variation of transport capacity in downstream branches. The model indicates that grain sorting tends to reduce the degree of flux asymmetry between branches for increasing heterogeneity of the mixture. Moreover, the uneven discharge distribution is associated with a different bed surface composition, with bed coarsening of the dominating channel and fining of the other branch. The reduced sediment transport asymmetry and bed surface fining enhance the transport of fine material in the less‐carrying branch, thus contributing to keep it morphologically active. Finally, the model predicts an overall fining of bed surface material with respect to the feeder channel. Plain Language Summary: River bifurcations occur when the main channel course splits into two secondary branches. The partition of sediments between these branches is essential to define whether bifurcations are morphologically stable in time, preventing sedimentation, and abandonment of the smaller channel. In this paper, we formulate a mathematical model to study how sediments of different sizes divide at bifurcations in morphodynamic equilibrium. Specifically, we consider two classes of sediment particles (e.g., fine and coarse gravel) and we investigate the role of the key mechanisms driving the sediment transport: the gravitational effect, which tends to move downhill coarse particles; and the selective transport effect, which promotes the mobility of coarse particles within the most‐carrying branch. These two mechanisms are found to bring contrasting effects, but the net results are clear. First, flow asymmetry is found to reduce with respect to the case where sediment particles of uniform size are considered. Second, the bed composition of the smaller branch becomes finer, contributing to maintain a significant sediment transport. These effects can explain patterns observed in gravel‐bed river bifurcations, and suggest how adjustments of bed composition can contribute to maintaining all branches active in the long term. Key Points: Grain sorting reduces water and sediment flux asymmetry between downstream bifurcatesThe less‐carrying branch undergoes significant fining, which enhances its sediment transport capacityThe overall bed composition of downstream branches is finer than that of the feeder channel [ABSTRACT FROM AUTHOR]

The authors report on the characterization at the single‐defect level of germanium‐vacancy (GeV) centers in diamond produced upon Ge− ion implantation and different subsequent annealing processes, with a specific focus on the effect of high‐pressure‐high‐temperature (HPHT) processing on their quantum‐optical properties. Different post‐implantation annealing conditions are explored for the optimal activation of GeV centers, namely, 900 °C 2 h, 1000 °C 10 h, 1500 °C 1 h under high vacuum, and 2000 °C 15 min at 6 GPa pressure. A systematic analysis of the relevant emission properties, including the emission intensity in saturation regime and the excited state radiative lifetime, is performed on the basis of a set of ion‐implanted samples, with the scope of identifying the most suitable conditions for the creation of GeV centers with optimal quantum‐optical emission properties. The main performance parameter adopted here to describe the excitation efficiency of GeV centers as single‐photon emitters is the ratio between the saturation optical excitation power and the emission intensity at saturation. The results show an up to eightfold emission efficiency increase in HPHT‐treated samples with respect to conventional annealing in vacuum conditions, suggesting a suitable thermodynamic pathway toward the repeatable fabrication of ultra‐bright GeV centers for single‐photon generation purposes. [ABSTRACT FROM AUTHOR]

Neuroinformatics is a research field that focusses on software tools capable of identifying, analysing, modelling, organising and sharing multiscale neuroscience data. Neuroinformatics has exploded in the last two decades with the emergence of the Big Data phenomenon, characterised by the so‐called 3Vs (volume, velocity and variety), which provided neuroscientists with an improved ability to acquire and process data faster and more cheaply thanks to technical improvements in clinical, genomic and radiological technologies. This situation has led to a 'data deluge', as neuroscientists can routinely collect more study data in a few days than they could in a year just a decade ago. To address this phenomenon, several neuroimaging‐focussed neuroinformatics platforms have emerged, funded by national or transnational agencies, with the following goals: (i) development of tools for archiving and organising analytical data (XNAT, REDCap and LabKey); (ii) development of data‐driven models evolving from reductionist approaches to multidimensional models (RIN, IVN, HBD, EuroPOND, E‐DADS and GAAIN BRAIN); and (iii) development of e‐infrastructures to provide sufficient computational power and storage resources (neuGRID, HBP‐EBRAINS, LONI and CONP). Although the scenario is still fragmented, there are technological and economical attempts at both national and international levels to introduce high standards for open and Findable, Accessible, Interoperable and Reusable (FAIR) neuroscience worldwide. [ABSTRACT FROM AUTHOR]

Climate change is expected to alter the distribution of flow discharge in rivers worldwide. We study the impact of climate‐driven flow changes on the shape of riverbed, and specifically on alternate bars, large deposits of gravel/sand that often form in rivers. We consider the illustrative example of the Alpine Rhine River, showing two nearby reaches with similar hydro‐morphological characteristics, but different channel width. Hydrological projections are obtained from literature, while the evolution of alternate bars is predicted through a novel, semi‐analytical model. Results show a remarkably different behavior of the two reaches: the upstream one, being wide enough for a full development of alternate bars, is resistant to flow alterations; the downstream reach, whose width is close to threshold conditions, is highly susceptible to future changes, showing a strong tendency to increase bar prominence. These findings reflect a general tendency of near‐threshold geomorphic systems to be vulnerable to anthropic stressors. Plain Language Summary: The worldwide alteration of the river flow induced by climate change is likely to significantly impact the bed morphology of embanked rivers, which is often characterized by the presence of alternate bars, namely repetitive sequences of large sediment deposits and scour zones. Bar formation is both a major issue for river management (due to local erosion at instream structures and increase of flood risk), and an important resource for sustaining biodiversity, because bar morphology templates rich habitats for river fauna and vegetation. We analyze the effect of climate change on river bars by considering existing state‐of‐the‐art projections of future flow discharge, and by implementing a mathematical model suitable to perform long‐term simulations, while keeping the essential ingredients to reproduce bar dynamics. Model results reveal a very different adaptation of the riverbed to climate change: relatively wide reaches are expected to maintain the current alternate bar characteristics, while reaches whose width is close to a critical threshold value are likely to experience a remarkable alteration in the next decades, which provides a noteworthy example of how near‐threshold geomorphic systems may be highly sensitive to climate change. Key Points: Climate‐driven changes of hydrological regime can have a significant impact on bar morphologyThe formation of alternate bars in channelized rivers is promoted by a decrease of frequency of high flowsSensitivity of bar morphology to climatic stressors depends on how far the river width is from the key morphodynamic threshold value [ABSTRACT FROM AUTHOR]

In this work, a green synthetic approach to 5,5′‐[oxybis(methylene)]bis‐2‐furfural (OBMF) from 5‐hydroxymethyl‐2‐furfural (HMF) is reported for the first time. In the optimized reaction conditions, dimethyl carbonate (DMC) is used as the preferred green solvent and iron(III) sulfate as the best catalyst, recyclable up to three times. The HMF self‐etherification reaction is conducted both in milligram‐ and gram‐scale with isolated yields up to 99% and 81% respectively. OBMF is further derivatized via reduction to achieve 5,5′‐oxybis(methylene)bis(furan‐5,2‐diyl)dimethanol (OBMF‐H), a potential bisphenol‐A biobased alternative. Thus, methoxycarbonylation of OBMF‐H leads to the biscarboxymethylated derivative (OBMF‐DC) employing, once again, DMC as solvent and reagent. Both OBMF‐H and OBMF‐DC are achieved in high yields and are fully characterized. Furthermore, thermogravimetric analysis of OBMF, OBMF‐H, and OBMF‐DC establishes that these compounds are more thermally stable than HMF and its derivatives. In fact, they can withstand up to 200 °C before undergoing complete degradation rendering OBMF and its derivatives valuable bio‐based monomers for bioplastics prepared via polycondensation reaction. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative diseases lead to memory disorders and cognitive impairments with major impacts on day‐to‐day function. Early detection of patients is essential for an efficient care approach, and differential diagnosis is essential for determining prognosis and tailoring management. Most research studies compare patients by pairwise comparison methods, but this does not correspond to daily clinical practice, in which clinicians need to distinguish many different possible types of dementia concomitantly. It has been shown that magnetic resonance imaging (MRI) can mark with good accuracy the different types of dementia, such as: Alzheimer's disease (AD), Frontotemporal dementia (FTD), Parkinson's disease (PD), dementia with Lewy bodies (DLB). Recently, Deep Learning approaches have started being used although differential diagnosis is still almost ignored. The aim of this study was to develop a Convolution Neural Network (CNN) to classify probable AD, FTD, DLB, PD and healthy elderly control (CN) subjects starting from Diffusion Tensor Imaging (DTI). Method: The cohort used in this study came from six different initiatives: ADNI1, NIFD2, NACC3, PDBP4, PPMI5 and Newcastle University6,7,8,9. We analysed a total of 108 CN, 110 AD, 135 FTD, 150 DLB, 132 PD. Demographic and neuropsychological characterization is shown in Table 1. The DTI scans were pre‐processed using the FMRIB software library (FSL) with eddy current correction, skull‐stripping and diffusion tensor calculation. We post‐processed the Fractional Anisotropy (FA) map using 3D CNN. The proposed CNN structure consisted of an image input layer, convolutional filters, several batch normalization with max‐pooling layers and, finally, the classification layer. A data augmentation approach was adopted that ultimately resulted in a dataset of 26'450 brain scans. A hold‐out validation (70% training set 30% test set) was performed. Result: We found excellent performance of the 3D CNN in discriminating the different neurodegenerative diseases. Figure 1 shows the confusion matrix with the following values for the area under the ROC curve in each class: 0.92 for CN, 0.90 for AD, 0.97 for DLB, 0.96 for FTD, 0.99 for PD. Conclusion: These results prove that Deep Learning and the 3D CCN method are suitable for clinical practice and provide additional clues that can help clinicians in diagnosis making. [ABSTRACT FROM AUTHOR]

Looping patterns, where channels divide and reconnect further downstream, are widespread in natural rivers. Here, we build an extensive dataset of different gravel‐bed and sand‐bed rivers around the world encompassing a wide range of physiographic and sedimentological conditions. Field data show the existence of quasi‐universal relations for the anabranches length when scaled with bankfull hydraulic geometry variables of the main upstream channel. The dimensionless length is found to be nearly slope‐invariant, identifying a clear difference with respect to deltaic systems. This scaling relationship is explained by interpreting the dynamics of river loops as basically controlled by a two‐way interaction between their constitutive elements, bifurcations and confluences. The identification of a quasi‐universal length scale provides insight on the morphological evolution of multi‐thread networks and constitutes a key information for the design of self‐sustaining river restoration interventions. Plain Language Summary: River loops, where the water course splits into smaller branches that reconnect further downstream, are ubiquitous in natural environments. A deeper understanding of their spatial structure can greatly improve the effectiveness and sustainability of common practices in river restoration, where multiple channels are reactivated to recover the ecological functions of harmed riverine ecosystems. The analysis of many different rivers worldwide shows that the length of river loops is not randomly distributed but follows a characteristic law. In particular, the average length of bifurcating branches is found to be proportional to the hydraulic parameters (width, depth) of the main upstream channel, regardless of the specific climatic or geologic context. This relationship is explained in terms of the key physical mechanisms that control the distribution of water and sediment between the branches. Key Points: River anabranches show a characteristic length set by bankfull hydraulic geometry parameters of the main channelThe anabranches length is unrelated to backwater length, thus marking a clear difference with respect to deltaic systemsField evidence is theoretically explained as the result of morphodynamic interaction between bifurcation and confluence nodes [ABSTRACT FROM AUTHOR]

Background: The choroid plexus (CP) is a structure located inside the brain ventricles and is responsible for the production of cerebrospinal fluid (CSF), transport of proteins across the epithelium to the CSF and clearance of proteins from the CSF. The CP undergoes changes with aging, which are exacerbated in Alzheimer's disease (AD) and could alter CP functioning. Nonetheless, the relation between CP functioning and AD pathophysiology is still unclear. Here, we investigated the association of CP volume with levels of CSF proteins predominantly expressed by the CP and amyloid positivity in non‐demented individuals. Method: We included 235 individuals with normal cognition (NC) or mild cognitive impairment (MCI) from the European EMIF‐AD MBD study (49% women, mean age 67.9 (SD 7.9) years). Based on CSF Aβ1‐42 (A, data‐driven cut‐offs) and p‐tau (T, center‐specific cut‐offs), individuals were classified as cognitively normal with normal A and T (controls, n=54). Based on CSF Aβ1‐42, individuals with NC or MCI were classified as amyloid‐positive (CN A+, n=61; MCI A+, n=67). CSF proteomic data were centrally generated using TMT mass spectrometry and 5 CSF proteins with predominant expression in the CP were selected based on the Protein Atlas, Harmonizome and literature (TTR, MFRP, SLC5A5, FOLR1, SOD3). CP and hippocampal volumes on MRI were quantified using FreeSurfer. We used non‐parametric (Spearman) partial correlations corrected for age, gender and total intracranial volume (TIV). Result: Lower Aβ42 levels were associated with higher CP volume in MCI (Figure 1). Higher levels of CP predominant expressed proteins were generally associated with increased CP volume in persons with amyloid positivity, in both preclinical and prodromal AD (Table 1). Lower Aβ42 levels were associated with lower hippocampal volume in MCI (Figure 2). Lower hippocampal volumes were associated with higher CP volumes in MCI (Figure 3). Nonetheless, hippocampal volume and the levels of CP predominant expressed proteins were generally not correlated (Table 2). Conclusion: Our findings suggest that CP volume is associated with levels of proteins predominantly expressed by the CP in predementia stages of AD. This would suggest CP dysfunction in early AD. This is important for future research and AD treatment development. [ABSTRACT FROM AUTHOR]

Background: The advent of big data and artificial intelligence has energized the neuroimaging community with powerful processing tools and the need for large‐scale computational resources for data analysis has increased. Not all neuroscientists have access to extensive resources or have sufficient expertise to configure these libraries, making them difficult to use. Method: A collection of popular MRI scan processing software, (i.e.: Fsl, FreeSurfer, Ants, SPM, Adaboost, Neuromorphometrics, LPA, Tracula) was selected as a proof of concept to be included in the NeuGRID Workflow to produce an advanced tool for group analysis and biomarkers assessment. Result: The NeuGRID Workflow was designed to allow the user to build a custom MRI processing pipeline by means of a layered structure (Fig.1) available for users at the URL https://neugrid2.eu/index.php/workflowgroup. In the first layer, the user must upload a compressed file containing T13D, FLAIR, and DWI scans of subjects. In the second layer, the user selects which kind of MRI sequence to process. If DICOMs were uploaded, the third layer provides tools to convert DICOMs into NIFTI, the default format for all subsequent workflow processes. All DICOMs are anonymized upon upload. The fourth layer allows the user to choose how images are preprocessed, and the preprocessing pipelines can be customized for different modalities. In the final layer, the user can choose how to analyze the images to calculate volume, thickness, area and curvature of brain regions, quantify white‐matter lesions and reconstruct major white‐matter pathways. The triggered job is efficiently parallelized using a Sun Grid Engine scheduler to reduce computation time. After the scans are processed in the NeuGRID cluster (450 CPUs, 2.5TB memory, 400TB storage), the user is notified by email that the job is finished and the results can be downloaded. Conclusion: The NeuGRID Workflow is a practical tool that allows researchers without computational resources and/or expertise to design a custom pipeline to process large amounts of data from anywhere using a traditional laptop or personal computer. The collection of heterogeneous tools provides a high degree of freedom in pipeline design, making NeuGRID Workflow a Swiss Army knife for MRI processing [ABSTRACT FROM AUTHOR]

Sacrocaudal luxation can be associated with sacral and caudal nerve roots injury, potentially leading to loss of tail nociception, tail paralysis and urinary incontinence. In cats, several treatments have been proposed depending on the patient's neurological status. When sacrocaudal luxation is associated with loss of tail nociception, tail paralysis and preserved urinary continence, surgical stabilisation can be envisaged. This case report describes surgical reduction and stabilisation of sacrocaudal fracture‐luxation in a large 4‐year‐old crossbreed dog. On presentation tail motor and sensory function (tested at the tail base) were absent. Tail exploration/stabilisation with transarticular Kirshner pins and tension band wires was performed. Motor function returned over 14 days following surgery. Maintenance of sacrocaudal alignment was confirmed radiographically as long as two months following surgery. To the authors' knowledge, there is little information concerning prognosis for tail mobility recovery and surgical treatment efficacy for dogs. Moreover, several anatomical differences existed between cats' and dogs' tails which must be considered during tail stabilisation. [ABSTRACT FROM AUTHOR]

Migrating bars are large‐scale, alternate bedforms that often develop in channelized river reaches, as a consequence of an intrinsic instability of the erodible channel bed. Their behavior under steady flow conditions has been widely investigated by means of theoretical, experimental, and numerical models, which revealed that bar formation occurs when the width‐to‐depth ratio of the channel exceeds a critical threshold value. Conversely, no much information is available about the long‐term, average characteristics of alternate bars in the case of a complex flow regime, which makes the width‐to‐depth ratio highly variable in time. Starting from the state‐of‐the‐art theoretical models of bar dynamics, we propose a novel methodology to determine the long‐term bar response to the hydrological river regime and the associated "bar‐forming" discharge that, if applied steadily, would produce the same morphological response. We derive a generalized criterion to define whether bars are expected to form and to estimate the long‐term bar topography, depending on flow probability density function and channel characteristics (width, slope and sediment size). Our procedure differs from the classical methods to define formative discharge, inasmuch as it accounts for the specific and reversible response of bar topography to the different flow stages that compose the hydrological regime. Application to four different gravel bed reaches in the Alpine region shows the capability of the procedure to interpret remarkably different riverbed morphologies and to provide a reasonable prediction of the observed bar height, thus suggesting its potential to analyze long‐term morphological trajectories following hydrological alterations and river restoration projects. Plain Language Summary: Alternate bars are large bedforms that can spontaneously develop in rivers. They often represent an issue in river management since they affect navigation, increase the flooding risk and interact with instream structures. A number of studies is available to predict the characteristics of alternate bars under constant‐discharge conditions. Conversely, the long‐term response of the average bar topography to a complex sequence of flood events is to a large extent unexplored. In this work, we propose a novel theoretically based procedure to assess whether alternate bars are expected to form in a river, to predict the average bar height, and to estimate the equivalent, bar‐forming discharge that can be effectively used in constant‐discharge models. This method may be used for evaluating the response of alternate bars to modifications of the hydrological flow regime (e.g., due to climate changes or hydropower production) or river restoration interventions (e.g., enlargement or narrowing of the channel width). Key Points: We propose a theoretically based method for predicting the long‐term response of migrating bars to the hydrological regimeOur procedure allows for determining whether alternate bars are expected to form, and for predicting their average heightWe define a bar‐forming discharge that, if applied steadily, would produce the same morphology as the full hydrological regime [ABSTRACT FROM AUTHOR]

Multithread fluvial environments like anastomosing and braided rivers are fundamentally directed by the continuous concatenation of channel bifurcations and confluences, which distribute flow and sediment among different branches that are reconnecting further downstream. A large number of theoretical, experimental, and numerical studies conducted in the last two decades have provided a clear picture of stability conditions for river bifurcations. However, most analyses are focused on the dynamics of bifurcations alone, ignoring the possible mutual interaction with downstream confluences. In this work, we study the morphodynamic equilibrium and stability conditions of a bifurcation‐confluence loop, where flow splits in two secondary anabranches that rejoin after a prescribed distance. Through the formulation of a novel theoretical model for mobile bed confluences, we show that the dominating anabranch (i.e., that carrying most discharge) is subject to an increase of the water surface elevation that is proportional to the square of the Froude number. This effect causes a decrease of the slope of the dominating anabranch, which acts as a negative feedback that increases the stability of the bifurcation‐confluence system. A linear analysis of the coupled model reveals that the stabilizing effect exerted by the confluence depends on the ratio between the length of the anabranches and the average water depth, independently of channel slope and Froude number. Ultimately, this effect is potentially able to stabilize the loop even when the sediment is mainly transported in suspension, a condition which makes the classic stabilizing mechanism (i.e., the topographic effect at the bifurcation node) practically ineffective. Key Points: The dominating branch of a channel confluence shows a higher water level, depending on the square of the Froude numberThe confluence exerts a negative feedback on the upstream bifurcation, which promotes the stability of the systemThe bifurcation‐confluence system can be stable even when the bedload steering at the bifurcation is very weak [ABSTRACT FROM AUTHOR]

To understand the mechanisms of N3 sleep interruptions in patients with sleepwalking episodes and/or sleep terrors (SW/ST), we evaluated whether autonomic reactions preceded or accompanied behavioural arousals from NREM sleep stage N3. In 20 adult patients with SW/ST and 20 matched controls without parasomnia, heart rate and pulse wave amplitude were measured beat‐to‐beat during the 10 beats preceding and during the 15 beats succeeding a motor arousal from N3 sleep. Respiratory rate and amplitude were measured during the same 25 successive beats. In patients with SW/ST, the N3 arousals were associated with a 33% increase in heart rate, a 57% decrease in pulse wave amplitude (indicating a major vasoconstriction), a 24% increase in respiratory rate and a doubling of respiratory amplitude. Notably, tachycardia and vasoconstriction started 4 s before motor arousals. A similar profile (tachycardia and vasoconstriction gradually increasing from the 4 s preceding arousal and post‐arousal increase of respiratory amplitude, but no polypnea) was also observed, with a lower amplitude, during the less frequent 38 quiet N3 arousals in control subjects. Parasomniac arousals were associated with greater tachycardia, vasoconstriction and polypnea than quiet arousals, with the same pre‐arousal gradual increases in heart rate and vasoconstriction. Autonomic arousal occurs 4 s before motor arousal from N3 sleep in patients with SW/ST (with a higher adrenergic reaction than in controls), suggesting that an alarming event during sleep (possibly a worrying sleep mentation or a local subcortical arousal) causes the motor arousal. [ABSTRACT FROM AUTHOR]

New Finding: What is the central question of this study?Transition to supine posture induces an inspiratory load associated with cortical activation in awake healthy subjects. Some obstructive sleep apnoea patients exhibit this cortical activity in the sitting position contributing to the arousal‐dependent compensation of their upper airway abnormalities. Does a transition to the supine posture in awake obstructive sleep apnoea patients increase this cortical activity?What is the main finding and its importance?The transition to supine posture induces a reduction in the cortical activity despite evidence of an increase in genioglossus activity, suggesting that genioglossus activation is not driven by cortical activity. The anatomy and mechanical properties of the upper airway (UA) depend on posture. Lying in a supine position causes cephalad fluid shift to the neck, thus narrowing the UA and predisposing the individual to obstructive sleep apnoea (OSA). Increased UA dilator muscle activity during wakefulness prevents the UA collapse but the underlying mechanism has not yet been elucidated. In the sitting position during wakefulness, some OSA patients exhibit preinspiratory cortical activity (preinspiratory potential, PIP) probably related to UA abnormalities. The aim of this study was to investigate changes in the preinspiratory cortical activity and UA dilator muscle in OSA patients during postural challenge. An electroencephalogram was used to detect PIP, and the genioglossus electromyographic activity and ventilation were analysed in 17 awake, male OSA patients while they were sitting, just after lying down, and then in response to leg positive pressure to enhance cephalad fluid shift. The prevalence of PIP decreased from 53% (sitting) to 12% (supine) (P = 0.002) in association with increased genioglossus activity (tonic from median (25th, 75th centiles) 2.3 (1.8, 2.8)% to 3.6 (1.7, 5.0)% of voluntary deglutition, P = 0.019; phasic from 2.3 (1.9, 2.8)% to 3.7 (2.0, 6.1)%, P = 0.024), and with increased transcutaneous carbon dioxide pressure (from 43.0 (42.4, 44.2) to 44.6 (43.5, 45.2) mmHg). No change was observed during leg‐positive‐pressure application. Moving from the sitting position to the supine position reduces respiratory‐related premotor cortical activity in awake OSA patients. The concomitant increase in genioglossus activity, therefore, is not driven by cortical respiratory activity. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects?What is the main finding and its importance?Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea. Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre‐inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory‐related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty‐four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP [median (25th; 75th centiles) 440 (430; 520) versus 320 (275; 385) ml, P = 0.018], without any other differences. From before to during leg positive pressure, PIP disappeared (P = 0.006). These results indicate that moving from sitting to lying induces transient respiratory‐related cortical activity in awake healthy subjects with greater fluid shift, supporting possible cortical participation in the response to upper airway loading induced by moving from sitting upright to lying supine. This study offers new perspectives in the understanding of obstructive sleep apnoea pathogenesis. [ABSTRACT FROM AUTHOR]

Water and sediment distribution by river bifurcations is often highly unbalanced. This may result from a variety of factors, such as migration of bars, channel curvature and backwater effects, which promote an uneven partition of flow and sediment fluxes in the downstream branches, which we call 'forcings'. Bifurcations also display an intrinsic instability mechanism that leads to unbalanced configurations, as occurs in the idealized case of a geometrically symmetric bifurcation, which we call 'free', provided the width‐to‐depth ratio of the incoming flow is large enough. Most frequently, these free and forced mechanisms coexist; however, their controlling roles in bifurcation dynamics have not been investigated so far. In this paper we address this question by proposing a unified free‐forced modelling framework for bifurcation morphodynamics. Upstream channel curvature and different slopes of downstream branches (slope advantage) are specifically investigated as forcing effects typically occurring in bifurcations of alluvial channels. The modelling strategy is based on the widely used two‐cell model of Bolla Pittaluga et al. (Water Resources Research, 2003, 39(3), 1–13), here extended to account for the spatially non‐uniform fluxes entering the bifurcation node. Results reveal that the relative role of free and forced mechanisms depends on the width‐to‐depth ratio falling above or below the resonant threshold that controls the stability of free bifurcations: when the main channel is relatively wide and shallow (super‐resonant regime) the bifurcation invariably evolves towards unbalanced configurations, whatever the combination of curvature and slope advantage values, which instead control the bifurcation response under sub‐resonant conditions. Detection of the resonant aspect ratio as a key threshold also releases the modelling approach from the need for parameter calibration that characterized previous approaches, and allows for interpreting under a unified framework the opposite behaviours shown by gravel‐bed and sand‐bed bifurcations for increasing Shields parameter values. © 2018 John Wiley & Sons, Ltd. We propose a theoretical framework for investigating the interaction between two different mechanisms that can break the symmetry of river bifurcations: (i) the free, autogenic instability; (ii) the forcing effect that may derive from the curvature of the upstream channel and/or from different downstream slopes. Results reveal that the bifurcation response to changing conditions depends on the aspect ratio of the main channel falling above or below the resonant threshold that controls the possibility of upstream morphodynamic influence. [ABSTRACT FROM AUTHOR]

Abstract: Measurement and estimation of bed load transport in gravel bed rivers are highly affected by its temporal fluctuations. Such variability is primarily driven by the flow regime but is also associated with a variety of inherent channel processes, such as flow turbulence, grain entrainment, and bed forms migration. These internal and external controls often act at comparable time scales, and are therefore difficult to disentangle, thus hindering the study of bed load variability under unsteady flow regime. In this paper, we report on laboratory experiments performed in a large, mobile bed flume where typical hydromorphological conditions of gravel bed rivers were reproduced. Data from a large number of replicated runs, including triangular and square‐wave hydrographs, were used to build a statistically sound description of sediment transport processes. We found that the inherent variability of bed load flux strongly depends on the sampling interval, and it is significantly higher in complex, wandering or braided channels. This variability can be filtered out by computing the mean response over the experimental replicates, which allows us to highlight two distinctive phenomena: (i) an overshooting (undershooting) response of the mean bed load flux to a sudden increase (decrease) of discharge, and (ii) a clockwise hysteresis in the sediment rating curve. We then provide an interpretation of these findings through a conceptual mathematical model, showing how both phenomena are associated with a lagging morphological adaptation to unsteady flow. Overall, this work provides basic information for evaluating, monitoring, and managing gravel transport in morphologically active rivers. [ABSTRACT FROM AUTHOR]

Introduction Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. Methods Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini–Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. Results An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of −8.0% (95% credible interval: [−11.5, −5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18 F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (−8.5, CrI: [−11.5, −5.6]; −14.1, CrI: [−19.3, −8.8]; −10.6, CrI: [−14.6, −6.1], respectively). Discussion There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup. [ABSTRACT FROM AUTHOR]

Monitoring sediment transport in morphologically complex and labile channels remains a difficult task, even at the laboratory scale. To address this challenge, a fully automated imagery technique for continuously mapping the spatial and temporal variability of bedload transport is proposed. This method uses differentiated time-lapse imagery taken from a fixed camera to detect bed variations induced by grain displacement. The technique is not based on tracking the individual particles; rather, it evaluates macroscopic colour changes within a region that contains several grains, which depend on the occurrence and intensity of the bedload transport. Image-derived data were compared with the sediment flux measured during four flume experiments, and produced good correspondence. The method provides continuous tracking of the location of the transporting channels, and enables estimation of local variations in the magnitude of the bedload flux. Moreover, the spatial extent of the monitoring area offers an unprecedented opportunity to aggregate spatially dense and continuous data at the reach scale, as needed to properly capture the full range of variability of morphologically complex and rapidly evolving gravel-bed rivers. Despite being limited to laboratory-scale physical experiments, the method provides useful data to investigate fundamental morphodynamic processes such as bar migration, bank erosion, anabranches opening/closure, and the associate spatial and temporal scales. Further, the data obtained have the potential to enhance numerical model calibration and improve our understanding of the complex dynamics of real-world settings. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Both types of sleep-disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo-ventilation (ASV) in such patients reduces morbidity and mortality.Aim: ADVENT-HF is designed to assess the effects of treating SDB with ASV on morbidity and mortality in patients with HFrEF.Methods: ADVENT-HF is a multicentre, multinational, randomized, parallel-group, open-label trial with blinded assessment of endpoints of standard medical therapy for HFrEF alone vs. with the addition of ASV in patients with HFrEF and SDB. Patients with a history of HFrEF undergo echocardiography and polysomnography. Those with a left ventricular ejection fraction ≤45% and SDB (apnoea-hypopnoea index ≥15) are eligible. SDB is stratified into OSA with ≥50% of events obstructive or CSA with >50% of events central. Those with OSA must not have excessive daytime sleepiness (Epworth score of ≤10). Patients are then randomized to receive or not receive ASV. The primary outcome is the composite of all-cause mortality, cardiovascular hospital admissions, new-onset atrial fibrillation requiring anti-coagulation but not hospitalization, and delivery of an appropriate discharge from an implantable cardioverter-defibrillator not resulting in hospitalization during a maximum follow-up time of 5 years.Conclusion: The ADVENT-HF trial will help to determine whether treating SDB by ASV in patients with HFrEF improves morbidity and mortality. [ABSTRACT FROM AUTHOR]

Assessing the conservation status of protected species needs quantitative population data, generally obtained using Capture-Mark-Recapture methods ( CMR). The exploitation of natural marking (e.g. individual morphological traits) offers an interesting alternative, based on image analyses, which may result in a less manipulation of protected species compared to the typical artificial marking method., In our 2-year CMR study, we tested for the first time in the natural setting the feasibility and the application of the computer-aided photographic identification method of Rosalia alpina using the individual elytral spots as the natural marking. The I3 SC software was used for the photographic analysis., Data were collected from populations of two National Parks of central Italy during July-August in 2014 and 2015. We developed a standard procedure in order to optimise the image acquisition in the field and to acquire clear and comparable images, facilitating the I3 SC screening process., The results demonstrated that the computer-aided photographic identification of natural markings can be implemented in a CMR population study of R. alpina. Our image processing approach showed that using only the elytral central spot contours made the tracing contour process less time-consuming obtaining reliable results. Furthermore, I3 SC output scores were used to identify a threshold value for the identification of new individuals or recaptures, facilitating the final identification proposed by operators., Finally, we assessed the possibility of performing the methodology using a Citizen Science approach. [ABSTRACT FROM AUTHOR]

Understanding the role of external controls on the morphology of braided rivers is currently limited by the dearth of robust metrics to quantify and distinguish the diversity of channel form. Most existing measures are strongly dependent on river stage and unable to account for the three-dimensional complexity that is apparent in digital terrain models of braided rivers. In this paper, we introduce a simple, stage-independent morphological indicator that enables the analysis of reach-scale regime morphology as a function of slope, discharge, sediment size, and degree of confinement. The index is derived from the bed elevation frequency distribution and characterizes a statistical width-depth curve averaged longitudinally over multiple channel widths. In this way, we define a 'synthetic channel' described by a simple parameter that embeds information about the river morphological complexity. Under the assumption of uniform flow, this approach can be extended to provide estimates of the reach-averaged shear stress distribution, bed load flux, and at-a-station-variability of wetted width. We test this approach using data from a wide range of labile channels including 58 flume experiments and three gravel bed braided rivers. Results demonstrate a strong relationship between the unit discharge and the shape of the elevation distribution, which varies between a U shape for typical single-thread confined channels and a Y shape for multithread reaches. Finally, we discuss the use of the metric as a diagnostic index of river condition that may be used to support inferences about the river morphological trajectory. [ABSTRACT FROM AUTHOR]

Metal-insulator-metal capacitors (MIMCAP) with stoichiometric SrTiO3 dielectric were deposited stacking two strontium titanate (STO) layers, followed by intermixing the grain determining Sr-rich STO seed layer, with the Ti-rich STO top layer. The resulted stoichiometric SrTiO3 would have a structure with less defects as demonstrated by internal photoemission experiments. Consequently, the leakage current density is lower compared to Sr-rich STO which allow further equivalent oxide thickness downscaling. [ABSTRACT FROM AUTHOR]

In this paper, we introduce rare-earth hygroscopic oxide Gd2O3 as a novel switching material allowing extended reset operation as compared to standard state-of-the-art oxide like (Hf,Al)O2. We prepared 5 nm-thick oxide layers, as integrated between TiN and Hf electrodes in 1-transistor/1-resistor configuration. Using industry-relevant programming current I ≤ 10 µA and pulse width ≤1 µs, 40 nm-size TiN\Gd2O3\Hf cells allowed reaching a median memory window (MW) > × 70 while state-of-the-art materials exhibited MW < × 10 in the same conditions. Based on the large MW, high write endurance properties (>106 cycles), and good retention of Gd2O3-based cells (>5 days at 85 °C), verify algorithms allow reliable programming with low latency. [ABSTRACT FROM AUTHOR]

In this work, we prove that, for a current regime of 10 μA and using industry-relevant programming pulse-width, Cu/Al2O3-based conductive-bridging RAM (CBRAM) cells ensure reliably larger memory window (MW) than state-of-the-art oxygen-vacancy-based RRAM (OxRRAM) cells. Due to the intrinsically stochastic nature of the switching mechanism, the Ron and Roff values can be widely distributed, especially in a low-current regime, drastically reducing the overall memory window. For this reason, in this study we adopt a statistical approach, focusing on the tails of the distributions. Using a program-verify method we show that the larger median MW in CBRAM allows to program a MW ≥×10 using ×10 shorter programming time with respect to OxRRAM. Moreover, we show that, in order to ensure a MW >×10 after a fixed retention time, the programming time needs to be several decades larger for OxRRAM than for CBRAM. [ABSTRACT FROM AUTHOR]

Background: In recent years, statistical and machine learning algorithms allowed advancements in many fields of healthcare research, but such methods are still mostly used by technical experts. Their implementation in user‐friendly software/web interfaces is fundamental for their broader adoption by patient‐facing physicians. Method: A validated SuStaIn (Young et al, 2019, https://doi.org/10.1038/s41467-018-05892-0) model for atrophy patterns in Alzheimer's Disease (AD) was used as core for a web application. The model was trained using volumes of relevant brain regions of 1031 subjects from the Alzheimer's Disease Neuroimaging Initiative and validated using 731 subjects from the OASIS, PharmaCog and ViTA Cohorts. Biomarkers used to train and validate the model were corrected against the effects of age, sex, education, APOE genotype and total intracranial volume (TIV). The model was exploited in the web application for single‐case scenarios. The user is required to input age and sex of the subject and upload an MRI scan which is processed with Freesurfer 5.3 to extract relevant brain volumes. Volumes are corrected against the effects of sex, age and TIV and converted into z‐scores used to compute the most likely among the three subtypes defined by the model and stage the subject on the relative z‐scores progression sequence. Results are summarized in a report (Fig. 1) and sent to the user via e‐mail. The web application skips the correction against education and APOE genotype as these factors may be unavailable and their influence on volumes should be minor. The validity of the different correction procedure was tested by subtyping and staging 50 subjects from the training set using the web application. Outputs were compared with the results of the validated model. Result: The web application was built and deployed on the neuGRID platform, and it is available at https://www.neugrid2.eu/index.php/ml-tools/sustain/. All subjects tested on the web application were assigned the same subtype as the validated model, although an average difference equal to 2.2 positions was observed for the staging. Conclusion: This web application implementing a SuStaIn model for AD atrophy subtypes represents a first example of advanced data‐driven algorithms implemented in a user‐friendly tool usable by clinicians in daily practice. [ABSTRACT FROM AUTHOR]

Background α1-Antitrypsin (AAT) deficiency (AATD) is a genetic condition associated with early-onset panacinar emphysema and, less often, vascular disease. Recently, abnormal elastic properties of ascending aortic wall were described in ZZ genotype AATD subjects who incidentally showed an increased left ventricular mass. Materials and methods To evaluate biventricular dimensions, valvular apparatus, systolic and diastolic function, 33 AATD subjects with ZZ genotype and 33 healthy subjects matched for age and sex underwent a complete echocardiographic assessment. Results Compared to controls, AATD subjects showed increased left ventricular mass (160 ± 59 g vs. 121 ± 70 g, P < 0·001), a higher incidence of left and right ventricular diastolic dysfunction (30% vs. 16%, P < 0·001 and 45% vs. 20%, P < 0·001, respectively) and mitral valve prolapse (35% vs. 6%, P < 0·001). In contrast, there was no difference between the two groups in diameters and systolic function of both ventricles and in the ejection fraction of left ventricle. The functions of aortic and tricuspidal valves were also similar. Conclusions In the presence of greater left ventricular mass, a significantly higher incidence of left and right ventricular diastolic dysfunction and mitral valve prolapse occurs in AATD subjects (ZZ genotype). These findings strongly suggest an abnormal remodelling process in cardiac tissue in AATD. [ABSTRACT FROM AUTHOR]

Background Hippocampal volumetry on magnetic resonance imaging is recognized as an Alzheimer's disease (AD) biomarker, and manual segmentation is the gold standard for measurement. However, a standard procedure is lacking. We operationalize and quantitate landmark differences to help a Delphi panel converge on a set of landmarks. Methods One hundred percent of anatomic landmark variability across 12 different protocols for manual segmentation was reduced into four segmentation units (the minimum hippocampus, the alveus/fimbria, the tail, and the subiculum), which were segmented on magnetic resonance images by expert raters to estimate reliability and AD-related atrophy. Results Intra- and interrater reliability were more than 0.96 and 0.92, respectively, except for the alveus/fimbria, which were 0.86 and 0.77, respectively. Of all AD-related atrophy, the minimum hippocampus contributed to 67%; tail, 24%; alveus/fimbria, 4%; and the subiculum, 5%. Conclusions Anatomic landmark variability in available protocols can be reduced to four discrete and measurable segmentation units. Their quantitative assessment will help a Delphi panel to define a set of landmarks for a harmonized protocol. [ABSTRACT FROM AUTHOR]

Background This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR)-based manual hippocampal segmentation. Methods The panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests. Results Agreement was significant on the inclusion of alveus/fimbria ( P = .021), whole hippocampal tail ( P = .013), medial border of the body according to visible morphology ( P = .0006), and on this combined set of features ( P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer’s disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates. Discussion Consensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol. [ABSTRACT FROM AUTHOR]

Background The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms. Methods Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction. Results Hippocampal volumes (mm 3 ) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer’s disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = <−0.468, P = <.0005). Cerebrospinal fluid spaces (mm 3 ) were as follows: controls: left = 23 (32), right = 25 (25); MCI: left = 15 (13), right = 22 (16); and AD: left = 11 (13), right = 20 (25). Five subjects (3.7%) presented with unusual anatomy. Conclusions This work provides reference hippocampal labels for the training and certification of automated segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol. [ABSTRACT FROM AUTHOR]

Background: Most of the studies that focus on the Alzheimer's disease (AD) prediction forecast a dementia label: cognitively normal, mild cognitive impairments or AD. However these labels cannot always be compared across cohorts, are not perfectly accurate and describe the disease thanks to a limited number of stages (only 3) which, in practice, is a continuous progression. For these reasons, we predict a cognitive test (MMSE) that has a finer discretization and is similarly assessed across cohorts. Method: The Bayesian mixed‐effects model introduced in (Schiratti et al. 2015, NIPS) allows to estimate the average temporal progression of a subset of scores from ADNI, out of the individual longitudinal data. This profile is personalized to individuals from the ADNI cohort but also AIBL and PharmaCOG. It allows to predict future values (1.5 to 6 years after the last seen visit). To measure the error of prediction, the value to predict is hidden and then compared to the prediction. This error is compared to the (i) constant prediction (i.e. no MMSE change), (ii) linear and (iii) logit regressions and (iv) the test‐retest MMSE noise ‐ whose standard deviation is 2.8 out of 30 (Clark et al, 1999, Archives of Neurology) ‐ which is the best achievable score. Result: The constant prediction, while being trivial, is better than the linear and logit regressions [Figure 1]. Moreover, it is of the order of the noise (i.e. best possible prediction) for horizons of less than 3 years. In any case, our prediction is of the noise order or smaller than the constant prediction, allowing to predict accurately the MMSE at any temporal horizon. Moreover, the accuracy on the AIBL and PharmaCOG [Figures 2 and 3] datasets highlights the potential of the model to generalize to patients from other cohorts but also in real‐life applications. Conclusion: The constant prediction outperforms standard regression techniques (linear and logit) due to the important noise level of the MMSE and the fact that the progression of the disease occurs over long periods of time. However, our model is able to beat this prediction for far enough temporal horizons. [ABSTRACT FROM AUTHOR]

Background: Understanding the path that leads from mild cognitive impairment (MCI) to Alzheimer's disease (AD) provides insights into dementia pathophysiology and can inform patient stratification in clinical trials. Our objective is to train statistical computational models for estimating an average disease trajectory to better understand how patients evolve on the basis of biomarkers of from the ADNI population, then validate the model on MCI subjects from the PharmaCog cohort. Method: The disease trajectory was built via a Gaussian Process Progression Model (GPPM) (Lorenzi et al. 2017, DOI: 10.1016/j.neuroimage.2017.08.059) trained on longitudinal biomarker data from 338 subjects in the ADNI database who had converted from MCI to AD at the time of writing. Biomarkers related to cognitive scores, cerebrospinal fluid and T13D magnetic resonance imaging were used to build the disease model. Validation was performed by staging 139 MCI subjects from the PharmaCog database, 20 of whom progressed to AD, along the progression model timeline. Only baseline cross sectional measures of biomarkers were used to stage PharmaCog subjects in order to simulate clinical settings. Measures of sensitivity, specificity, balanced accuracy and area under curve (AUC) were used to measure the staging performance. Result: The staging of PharmaCog subjects shows a clear separation between MCI stable (sMCI) subjects and MCI progressors (pMCI) on the disease timeline. On average, sMCIs were staged at year 72.7±3.6 while pMCIs are staged 3 years later (p‐value<0.01) at year 75.5±2.8. Classification of sMCI vs pMCI subjects returned a sensitivity equal to 0.68, specificity equal to 0.85, balanced accuracy equal to 0.77 and the ROC curve (Figure 1) had AUC equal to 0.75. Conclusion: We identified MCI converters to AD in a clinical data set (PharmaCog) using a data‐driven computational model of AD progression trained on research data (ADNI). Classification performance was comparable to other data‐driven tools (Young et al., 2014, DOI: 10.1093/brain/awu176), but performed in a more challenging clinical setting. This validates the staging efficacy of such models and shows their utility for future application in healthcare and clinical trials. [ABSTRACT FROM AUTHOR]

Background: Heterogeneity of cohorts, in terms of inclusion criteria, design of follow‐up visits and batteries of cognitive assessments, hinders any thorough comparisons between them. For that reason, we build a cross‐cohort model of cognitive decline that can be personalized to any patient, allowing to impute partially or totally missing scores. This enables to compare the subjects' progression across cohorts thanks to common cognitive assessments. Method: Based on a generic framework of disease progression that handles longitudinal data (Schiratti et al. 2015, NIPS) and implemented in the Leaspy Python package, we first estimate the joint progression of a large set of cognitive scores from the ADNI database along a common disease timeline. This group‐average progression is then personalized to individual trajectories of patients from the PharmaCog and AIBL cohorts. In particular, all individuals are characterized by a relative pace of progression and onset age that can be compared across cohorts. To validate our model, we impute missing values of a given score, based on its past and future values together with the dynamics of concurrent scores and compare errors to constant predictions and linear regressions. We finally go further by simulating purposely concealed scores thanks to the progression of the remaining features so to mock reconstruction of scores that are entirely missing in a particular cohort. Results: Figure 1 shows the relative positioning of all subjects from the 3 cohorts based on their individual pace of progression and their age at disease onset. Such characterization enables to impute missing values of the MMSE or the Immediate/Delayed Logical Memory better than imputing the last known value or fitting a linear regression [Figure 2]. Furthermore, from the multiple measurements of a single score, the model is able to reconstruct the individual progression of the other scores at the corresponding visits [Figure 3], with a controlled error rate. Conclusion: Our model enables comparison of patients trajectories from different cohorts. It permits to lessen imputation errors of most cognitive scores in new cohorts and demonstrates a new way to simulate, at any individual visit, scores that have not been measured in practice. [ABSTRACT FROM AUTHOR]

Cortical gray matter volume and resting state cortical electroencephalographic rhythms are typically abnormal in subjects with amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here we tested the hypothesis that in amnesic MCI and AD subjects, abnormalities of EEG rhythms are a functional reflection of cortical atrophy across the disease. Eyes-closed resting state EEG data were recorded in 57 healthy elderly (Nold), 102 amnesic MCI, and 108 AD patients. Cortical gray matter volume was indexed by magnetic resonance imaging recorded in the MCI and AD subjects according to Alzheimer's disease neuroimaging initiative project (http://www.adni-info.org/). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). These rhythms were indexed by LORETA. Compared with the Nold, the MCI showed a decrease in amplitude of alpha 1 sources. With respect to the Nold and MCI, the AD showed an amplitude increase of delta sources, along with a strong amplitude reduction of alpha 1 sources. In the MCI and AD subjects as a whole group, the lower the cortical gray matter volume, the higher the delta sources, the lower the alpha 1 sources. The better the score to cognitive tests the higher the gray matter volume, the lower the pathological delta sources, and the higher the alpha sources. These results suggest that in amnesic MCI and AD subjects, abnormalities of resting state cortical EEG rhythms are not epiphenomena but are strictly related to neurodegeneration (atrophy of cortical gray matter) and cognition. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim: Obstructive sleep apnoeas generate an intense afferent traffic leading to arousal and apnoea termination. Yet a decrease in the sensitivity of the afferents has been described in patients with obstructive sleep apnoea, and could be a determinant of disease severity. How mechanical changes within the respiratory system are processed in the brain can be studied through the analysis of airway occlusion-related respiratory-related evoked potentials. Respiratory-related evoked potentials have been found altered during sleep in mild and moderate obstructive sleep apnoea syndrome, with contradictory results during wake. We hypothesized that respiratory-related evoked potentials’ alterations during wake, if indeed a feature of the obstructive sleep apnoea syndrome, should be present in untreated severe patients. Methods: Ten untreated patients with severe obstructive sleep apnoea syndrome and eight matched controls were studied. Respiratory-related evoked potentials were recorded in Cz-C3 and Cz-C4, and described in terms of the amplitudes and latencies of their components P1, N1, P2 and N2. Results: Components amplitudes were similar in both groups. There was no significant difference in P1 latencies. This was also the case for N1 in Cz-C3. In contrast, N1 latencies in Cz-C4 were significantly longer in patients with obstructive sleep apnoea syndrome [median 98 ms (interquartile range 16·00) versus 79·5 ms (5·98), P = 0·015]. P2 and N2 were also significantly delayed, on both sides. Conclusions: The cortical processing of airway occlusion-related afferents seems abnormal in untreated patients with severe obstructive sleep apnoea syndrome. This could be either a severity marker and/or an aggravating factor. [ABSTRACT FROM AUTHOR]

Faced with mechanical inspiratory loading, awake animals and anaesthetized humans develop alveolar hypoventilation, whereas awake humans do defend ventilation. This points to a suprapontine compensatory mechanism instead of or in addition to the ‘traditional’ brainstem respiratory regulation. This study assesses the role of the cortical pre-motor representation of inspiratory muscles in this behaviour. Ten healthy subjects (age 19–34 years, three men) were studied during quiet breathing, CO2-stimulated breathing, inspiratory resistive loading, inspiratory threshold loading, and during self-paced voluntary sniffs. Pre-triggered ensemble averaging of Cz EEG epochs starting 2.5 s before the onset of inspiration was used to look for pre-motor activity. Pre-motor potentials were present during voluntary sniffs in all subjects (average latency (±s.d.): 1325 ± 521 ms), but also during inspiratory threshold loading (1427 ± 537 ms) and during inspiratory resistive loading (1109 ± 465 ms). Pre-motor potentials were systematically followed by motor potentials during inspiratory loading. Pre-motor potentials were lacking during quiet breathing (except in one case) and during CO2-stimulated breathing (except in two cases). The same pattern was observed during repeated experiments at an interval of several weeks in a subset of three subjects. The behavioural component of inspiratory loading compensation in awake humans could thus depend on higher cortical motor areas. Demonstrating a similar role of the cerebral cortex in the compensation of disease-related inspiratory loads (e.g. asthma attacks) would have important pathophysiological implications: it could for example contribute to explain why sleep is both altered and deleterious in such situations. [ABSTRACT FROM AUTHOR]

Changes in the soluble protein constitution of infected leaves have been reported to occur in Nicotiana species hypersensitively reacting to viruses (Gianinazzi, Vallée and Martin 1969, Gianinazzi, Martin and Vallée 1970, van Loon and van Kammen 1970, van Loon 1975, Khurana and Kawaguchi 1977, Rohloff and Lerch 1977, Ota and Taniguchi 1978, Gianinazzi, Ahl and Cornu 1981). In 'Samsun NN' and 'Xanthi n.c.' tobacco varieties, four new protein constituents have been demonstrated in virus inoculated leaves (Gianinazzi, Martin and Vallée 1970, van Loon and van Kammen 1970). The appearance of new protein components has also been reported in other host-virus hypersensitive combinations (Ladygina et al. 1977, Coutts 1978). A further generalization of this finding could lead to the conclusion that this phenomenon is a general feature, although not exclusive (Kassanis, Gianinazzi and White 1974), of the hypersensitive reaction to viruses. The role of these proteins, some of which have recently been purified and characterized (Antoniw et al. 1980) still remains to be explained. We report here a study on qualitative and quantitative changes in the soluble protein constitution of Gomphrena globosa leaves hypersensitively reacting to tomato bushy stunt virus (TBSV), tobacco mosaic virus (TMV) and potato virus X (PVX). Preliminary results on this subject, limited to one virus only, have already been stated at the 19th Congress of the Italian Society of Plant Physiology (Pennazio, Vecchiati and Redolfi 1980). [ABSTRACT FROM AUTHOR]

The endogenous primary amino acid derivative N'-Trimethyl-L-Lysine (TML) induces resistance in bean plants against the biotrophic fungi Uromyces phaseoli. The effectiveness of protection depends on the interval between treatment and inoculation of the plants and on the dosage of applicated TML. It acts as resistance inducer within two concentration ranges of 10-3-10-5 and 10-8-10-10 mol/l, respectively, if applied 6 or 8 days after inoculation. [ABSTRACT FROM AUTHOR]