Disruption Of Network Research Articles

Betweenness Centrality-Based seismic risk management for bridge transportation networks

Although bridges are integral parts of transportation networks, they are vulnerable to natural hazards. The damage incurred during these natural hazards events leads to network disruptions and hinders post-event recovery. Therefore, improving the seismic performance of transportation networks is critical. This paper proposes an origin–destination pair betweenness centrality (BC)-based methodology to rank bridges according to their importance in a complex bridge network. The proposed methodology is an easy-to-use approach that considers user equilibrium and topology and significantly shorten the computational time. In addition, this study proposes two strategies including the retrofit of bridges and construction of new bridges based on the BC importance of bridges to mitigate the seismic risk of bride networks. A well-studied bridge network in California was used to demonstrate the application and the effect of different strategies was compared in this study. Bridges located at the shortest path significantly affect the seismic performance of bridge networks, indicating there is no need to rehabilitate or replace all bridges under budget constraints. Also, constructing five new bridges based on BC importance improved seismic performance of the bridge network much more than retrofitting 21 bridges. Moreover, the proposed methodology presents a significant reduction in computational time (only 1/30 compared with an existing study) in resolving the importance of bridges in a network and can be applied to provide useful information for disaster management teams to mitigate the seismic risk of bridge networks.

JMJD2A participates in cytoskeletal remodeling to regulate castration-resistant prostate cancer docetaxel resistance

BackgroundTo investigate underlying mechanism of JMJD2A in regulating cytoskeleton remodeling in castration-resistant prostate cancer (CRPC) resistant to docetaxel.MethodsTissue samples from CRPC patients were collected, and the expression of JMJD2A, miR-34a and cytoskeleton remodeling-related proteins were evaluated by qPCR, western blot and immunohistochemistry, and pathological changes were observed by H&E staining. Further, JMJD2A, STMN1 and TUBB3 were knocked down using shRNA in CRPC cell lines, and cell viability, apoptosis and western blot assays were performed. The interaction between miR-34a/STMN1/β3-Tubulin was analyzed with dual-luciferase reporter and co-immunoprecipitation assays.ResultsIn clinical experiment, the CRPC-resistant group showed higher expression of JMJD2A, STMN1, α-Tubulin, β-Tubulin and F-actin, and lower expression of miR-34a and β3-Tubulin compared to the sensitive group. In vitro experiments showed that JMJD2A could regulate cytoskeletal remodeling through the miR-34a/STMN1/β3-Tubulin axis. The expression of miR-34a was elevated after knocking down JMJD2A, and miR-34a targeted STMN1. The overexpression of miR-34a was associated with a decreased expression of STMN1 and elevated expression of β3-Tubulin, which led to the disruption of the microtubule network, decreased cancer cell proliferation, cell cycle arrest in the G0/G1 phase, and increased apoptosis.ConclusionJMJD2A promoted docetaxel resistance in prostate cancer cells by regulating cytoskeleton remodeling through the miR-34a/STMN1/β3-Tubulin axis.

Mobility operator service capacity sharing contract design to risk-pool against network disruptions

We propose a new mechanism to design risk-pooling contracts between operators to improve service resilience during disruptions. We formulate a novel two-stage stochastic multicommodity flow model to determine the cost savings of a coalition under different disruption scenarios and solve it using L-shaped method along with sample average approximation. Computational tests are conducted for network instances with up to 1024 scenarios. The proposed model is applied to a regional multi-operator network in the Randstad area of the Netherlands, for four operators, 40 origin-destination pairs, and over 1400 links where disruption data is available. Using the proposed method, we identify stable cost allocations that could yield a 66% improvement in overall network performance over not having any risk-pooling contract in place. We illustrate the sensitivity of the HTM operator's bargaining power to different network structures and disruption scenarios.

Altered directional functional connectivity underlies post-stroke cognitive recovery.

Cortical ischaemic strokes result in cognitive deficits depending on the area of the affected brain. However, we have demonstrated that difficulties with attention and processing speed can occur even with small subcortical infarcts. Symptoms appear independent of lesion location, suggesting they arise from generalized disruption of cognitive networks. Longitudinal studies evaluating directional measures of functional connectivity in this population are lacking. We evaluated six patients with minor stroke exhibiting cognitive impairment 6-8 weeks post-infarct and four age-similar controls. Resting-state magnetoencephalography data were collected. Clinical and imaging evaluations of both groups were repeated 6- and 12 months later. Network Localized Granger Causality was used to determine differences in directional connectivity between groups and across visits, which were correlated with clinical performance. Directional connectivity patterns remained stable across visits for controls. After the stroke, inter-hemispheric connectivity between the frontoparietal cortex and the non-frontoparietal cortex significantly increased between visits 1 and 2, corresponding to uniform improvement in reaction times and cognitive scores. Initially, the majority of functional links originated from non-frontal areas contralateral to the lesion, connecting to ipsilesional brain regions. By visit 2, inter-hemispheric connections, directed from the ipsilesional to the contralesional cortex significantly increased. At visit 3, patients demonstrating continued favourable cognitive recovery showed less reliance on these inter-hemispheric connections. These changes were not observed in those without continued improvement. Our findings provide supporting evidence that the neural basis of early post-stroke cognitive dysfunction occurs at the network level, and continued recovery correlates with the evolution of inter-hemispheric connectivity.

Altered structural covariance of locus coeruleus in individuals with significant memory concern and patients with mild cognitive impairment.

The locus coeruleus (LC) is the site where tau accumulation is preferentially observed pathologically in Alzheimer's disease (AD) patients, but the changes in gray matter co-alteration patterns between the LC and the whole brain in the predementia phase of AD remain unclear. In this study, we estimated and compared the gray matter volume of the LC and its structural covariance (SC) with the whole brain among 161 normal healthy controls (HCs), 99 individuals with significant memory concern (SMC) and 131 patients with mild cognitive impairment (MCI). We found that SC decreased in MCI groups, which mainly involved the salience network and default mode network. These results imply that seeding from LC, the gray matter network disruption and disconnection appears early in the MCI group. The altered SC network seeding from the LC can serve as an imaging biomarker for discriminating the patients in the potential predementia phase of AD from the normal subjects.

PO-01-170 PHARMACOLOGICAL AND GENE-THERAPY BASED INHIBITION OF NOX2-GENERATED ROS ATTENUATES DISRUPTION OF MICROTUBULE NETWORK AND EMERGENCE OF TRIGGERED CA2+WAVES IN ATRIAL MYOCYTES AND IN CHRONIC AF CANINE MODEL

Recent research indicate an important role for derailed proteostasis in atrial fibrillation (AF). Major pathways of derailed proteostasis include disruption of microtubule network (MTN). Experimental and clinical studies have documented a significant contribution of histone deactylase 6 (HDAC6) mediated disruption of MTN. Another major causative factor for AF is excessive oxidative stress (OS). However, a clear connection of disruption of MTN with OS is not known in atrial myocytes and chronic model of AF. In particular, it remains elusive whether disruption of MTN by NOX2-generated reactive oxygen species (ROS) contributes to the emergence of triggered Ca2+ waves (TCWs), which can cause membrane depolarization and promote early-afterdepolarization (EAD). To establish the connection between OS and disruption of MTN in isolated canine atrial myocytes and in atrial myocardium of a canine model of chronic AF Normal atrial myocytes were isolated from 4 dogs and pre-incubated in Colchicine (a microtubule disruptor) and H2O2. While myocytes, loaded with Ca2+ sensitive dye, were paced at different cycle lengths (1000ms to 200ms), line-scan confocal Ca2+ imaging were performed in the presence of gp91-tat (a NOX2 inhibitor) and TSA (a HDAC6 inhibitor). In the same cells, MTN was examined by Immunofluorescence. To determine the MTN organization in chronic AF, immunohischemistry was performed in atrial tissue sections from 3 normal animals, 4 control rapid atrial pacing (RAP) animals, and 4 NOX2-shRNA injected RAP animals. In Colchicine treated- isolated atrial myocytes, acute application of gp91-tat and TSA attenuated the disruption of MTN (a) and the generation of TCWs (b). Similarly, gp91-tat and TSA attenuated the disruption of MTN in H2O2 pretreated atrial myocytes (data not shown). Notably, while distinctive MTN was abolished in RAP induced chronic AF atrial sections, there was an attenuation of expected MTN decrease in atrial sections from NOX2-shRNA injected RAP dogs (c). Inhibition of NOX2 by either NOX2 shRNA injection in the chronic AF model or acute application of NOX2 inhibitor as well as HDAC6 inhibitor in atrial myocytes is associated with attenuation of the disruption of MTN and generation of TCWs. Identifying the connection between OS and derailed proteostasis not only sheds light on the molecular mechanisms underlying AF, but also may allow to develop novel therapeutic approach for AF.

Comparative Study of the Seismic Resilience of Transportation Networks according to Bridge Recovery Priority

Recently, frequent earthquakes have damaged bridge structures, causing great inconvenience owing to the disruption of transportation networks and increasing travel time. In this study, the restoration priority of bridges under seismic conditions was proposed and the seismic resilience curves were compared based on an artificial neural network model. To determine the restoration priority of bridges, 1) performance-based and 2) benefit-cost-based restoration priorities were introduced. For demonstration purposes, the actual Pohang road network was reconstructed and the seismic resilience curves of the transportation network corresponding to the proposed restoration priorities were compared. Numerical analysis showed that the performance-based restoration priority had a more rapid seismic resilience curve than benefit-cost-based restoration priority.

Disrupted longitudinal restoration of brain connectivity during weight normalization in severe anorexia nervosa

Altered intrinsic brain connectivity of patients with anorexia nervosa has been observed in the acute phase of the disorder, but it remains unclear to what extent these alterations recover during weight normalization. In this study, we used functional imaging data from three time points to probe longitudinal changes in intrinsic connectivity patterns in patients with severe anorexia nervosa (BMI ≤ 15.5 kg/m2) over the course of weight normalization. At three distinct stages of inpatient treatment, we examined resting-state functional connectivity in 27 women with severe anorexia nervosa and 40 closely matched healthy controls. Using network-based statistics and graph-theoretic measures, we examined differences in global network strength, subnetworks with altered intrinsic connectivity, and global network topology. Patients with severe anorexia nervosa showed weakened intrinsic connectivity and altered network topology which did not recover during treatment. The persistent disruption of brain networks suggests sustained alterations of information processing in weight-recovered severe anorexia nervosa.

Structure, Location, and Spatial Proximities of Hydroxyls on γ-Alumina Crystallites by High-Resolution Solid-State NMR and DFT Modeling: Why Edges Hold the Key

The atomic-scale characterization of surface active sites on γ-alumina still represents a great challenge for numerous catalytic applications. Here, we combine advanced density functional theory (DFT) calculations with one- and two-dimensional proton solid-state NMR experiments to identify the exact location and the spatial proximity of hydroxyl groups on γ-alumina crystallites. Our approach relies on revisited models for the (100), (111), basal (110)b, and lateral (110)l facets of γ-alumina, as well as for the edges at their intersections. Notably, we show that the ≃0 ppm AlTd-μ1-OH protons are predominantly located on edges, where these are free from the H-bond network. The proximities among the AlTd-μ1-OH as well as with μ2-OH groups are revealed by 1H–1H dipolar correlation experiments and analyzed in the light of the DFT calculations, which identify their location on the basal (110)b facet and on the (110)b/(100) and (110)b/(110)l edges. Using chlorine atoms to probe the presence of hydroxyls, we show that the chlorination occurs selectively by exchanging μ1-OH located on edges and on lateral (110)l facets. By contrast, the basal (110)b and lateral (111) facets are not probed by Cl. This exchange explains the disappearance of the ≃0 ppm peak and of the correlations involving AlTd-μ1-OH species. Moreover, after chlorination, a deshielding of the AlTd is observed on high-resolution 27Al NMR spectra. More subtle effects are visible on the proton correlation spectra, which are attributed to the disruption of the H-bond network in the course of chlorination.

Impairment of Connexin 43 may initiate cilia decline in syringomyelia

Ependymal cilia, which are maintained by the Connexin 43 (Cx43) and protected by the actin network, play an essential role in regulating cerebrospinal fluid (CSF) circulation. The decline of ependymal cilia has been reported in syringomyelia, but the underlying mechanism remains unclear. In this study, we used an extradural compression-induced syringomyelia rat model to investigate the changes in cilia and related pathologies during the formation of syringomyelia. We divided rats into control and syringomyelia groups and sacrificed them at three time points, 7, 14, and 28 days postoperative (dpo). Scanning electron microscopy (SEM) and immunofluorescence (IF) were used to illustrate the number and morphology of ependymal cilia. IF was also used to show the status of centrioles, actin network, and Cx43 (the main component of the gap junction). Transmission electron microscopy (TEM) was used to observe the structure of the gap junction. The results showed that most syringomyelia were located at segments (T10–12) rostral to the compression site (T13). SEM images showed that the number of cilia in the central canal (CC) declined in two phases during the development of syringomyelia (early stage, 7 dpo; later stage, 14 and 28 dpo). The number of cilia showed a significant difference between the early and later stages of syringomyelia development. Additionally, TEM showed the absence of gap junction and IF illustrated less Cx43 expression in ependymal cells (ECs) at the compression site in both the early and later stages. Actin network disruption and centrioles reduction at adjacent segments rostral to the compression site were found in the later stage. These findings indicate that the loss of Cx43 at the compression site may be related to cilia detachment at rostral adjacent segments by disrupting intercellular communication in the early stage of syringomyelia development. This early cilia decline then causes actin network disorganization, further aggravating cilia decline by exposing centrioles to CSF shear stress in the later stage. These findings suggest a potential mechanism of ependymal cilia decline in the development of syringomyelia and may provide a novel perspective for future research in this area.

An update on pathogenesis and clinical scenario for Parkinson's disease: diagnosis and treatment.

In severe cases, Parkinson's disease causes uncontrolled movements known as motor symptoms such as dystonia, rigidity, bradykinesia, and tremors. Parkinson's disease also causes non-motor symptoms such as insomnia, constipation, depression and hysteria. Disruption of dopaminergic and non-dopaminergic neural networks in the substantia nigra pars compacta is a major cause of motor symptoms in Parkinson's disease. Furthermore, due to the difficulty of clinical diagnosis of Parkinson's disease, it is often misdiagnosed, highlighting the need for better methods of detection. Treatment of Parkinson's disease is also complicated due to the difficulties of medications passing across the blood-brain barrier. Moreover, the conventional methods fail to solve the aforementioned issues. As a result, new methods are needed to detect and treat Parkinson's disease. Improved diagnosis and treatment of Parkinson's disease can help avoid some of its devastating symptoms. This review explores how nanotechnology platforms, such as nanobiosensors and nanomedicine, have improved Parkinson's disease detection and treatment. Nanobiosensors integrate science and engineering principles to detect Parkinson's disease. The main advantages are their low cost, portability, and quick and precise analysis. Moreover, nanotechnology can transport medications in the form of nanoparticles across the blood-brain barrier. However, because nanobiosensors are a novel technology, their use in biological systems is limited. Nanobiosensors have the potential to disrupt cell metabolism and homeostasis, changing cellular molecular profiles and making it difficult to distinguish sensor-induced artifactsfrom fundamental biological phenomena. In the treatment of Parkinson's disease, nanoparticles, on the other hand, produce neurotoxicity, which is a challenge in the treatment of Parkinson's disease. Techniques must be developed to distinguish sensor-induced artifacts from fundamental biological phenomena and to reduce the neurotoxicity caused by nanoparticles.

Differential Control of Small-conductance Calcium-activated Potassium Channel Diffusion by Actin in Different Neuronal Subcompartments.

Small-conductance calcium-activated potassium (SK) channels show a ubiquitous distribution on neurons, in both somatodendritic and axonal regions. SK channels are associated with neuronal activity regulating action potential frequency, dendritic excitability, and synaptic plasticity. Although the physiology of SK channels and the mechanisms that control their surface expression levels have been investigated extensively, little is known about what controls SK channel diffusion in the neuronal plasma membrane. This aspect is important, as the diffusion of SK channels at the surface may control their localization and proximity to calcium channels, hence increasing the likelihood of SK channel activation by calcium. In this study, we successfully investigated the diffusion of SK channels labeled with quantum dots on human embryonic kidney cells and dissociated hippocampal neurons by combining a single-particle tracking method with total internal reflection fluorescence microscopy. We observed that actin filaments interfere with SK mobility, decreasing their diffusion coefficient. We also found that during neuronal maturation, SK channel diffusion was gradually inhibited in somatodendritic compartments. Importantly, we observed that axon barriers formed at approximately days in vitro 6 and restricted the diffusion of SK channels on the axon initial segment (AIS). However, after neuron maturation, SK channels on the AIS were strongly immobilized, even after disruption of the actin network, suggesting that crowding may cause this effect. Altogether, our work provides insight into how SK channels diffuse on the neuronal plasma membrane and how actin and membrane crowding impacts SK channel diffusion.

Resting-State Electroencephalography Reveals Three Subphenotypes of Parkinson’s Disease (P6-11.002)

<h3>Objective:</h3> To identify different Parkinson’s disease (PD) sub-phenotypes and their electrophysiological profile based on resting-state electroencephalography (RS-EEG). <h3>Background:</h3> Parkinson’s disease is a complex brain disorder characterised mainly by motor signs, with clinical evidence of cognitive and behavioural deficits in up to 40% of cases in early stage. Clinical and biological manifestations are very heterogeneous among individuals with PD and subgrouping was mainly performed using clinical parameters. However, these subgroups do not take into account underlying disease physiopathology, and were shown not entirely predictive of disease prognosis. <h3>Design/Methods:</h3> Resting-state electroencephalography (EEG) is a powerful tool to identify abnormal patterns of motor and cognitive deficits in PD. These disruptions have previously been identified across multiple frequency bands using cortical spectral power and functional connectivity from longitudinal high-density EEG recordings (baseline, 3 years follow-up and 5 years follow-up). In this study, using data-driven methods (similarity network fusion and source-space spectral analysis), we have performed a clustering analysis to identify disease sub-phenotypes and to determine whether different patterns of disruption are predictive of disease outcome. <h3>Results:</h3> We showed that PD patients (N = 44) can be subgrouped into three phenotypes with distinct electrophysiological profiles. These clusters are characterised by different levels of disruptions in the somatomotor network (delta and beta band), the frontotemporal network (alpha2 band) and the default mode network (alpha1 band), which consistently correlate with clinical profiles and disease courses. We showed that these clusters are statistically robust, and can predict the clinical trajectory and disease outcome. <h3>Conclusions:</h3> Our findings show that novel phenotyping using electric brain signal analysis can distinguish PD subtypes based exclusively on different patterns of brain oscillations. These patterns can reflect underlying disease neurobiology. Innovative profiling in PD has clear potential in patient’s stratification and can also support new therapeutic strategies that are brain-based and designed to modulate brain activity disruption. <b>Disclosure:</b> Mrs. Yassine has nothing to disclose. Ute Gschwandtner has nothing to disclose. Dr. Auffret has received personal compensation for serving as an employee of France Développement Electronique. The institution of Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. Dr. Auffret has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aguettant. The institution of Dr. Auffret has received research support from Association France Parkinson. The institution of Dr. Auffret has received research support from Homeperf. The institution of Dr. Auffret has received research support from LVL. The institution of Dr. Auffret has received research support from University of Rennes 1. The institution of Dr. Auffret has received research support from Aguettant. The institution of Dr. Auffret has received research support from Linde. The institution of Dr. Auffret has received research support from Plateforme Nationale pour la recherche sur la fin de vie. Dr. Auffret has received publishing royalties from a publication relating to health care. Dr. Duprez has nothing to disclose. Mr. Verin has nothing to disclose. The institution of Dr. Fuhr has received research support from Roche. Mr. HASSAN has nothing to disclose.

Influence of snow and meteorological conditions on snow‐avalanche deposit volumes and consequences for road‐network vulnerability

AbstractSnow avalanches are a major component of the mountain cryosphere that frequently create road obstructions. Deposit characteristics determine the extent of damage to the road infrastructures and the period of disruption of the road network, but the factors controlling snow‐deposit volumes remain largely unknown. This study investigates the influence of meteorological and snowpack conditions on snow‐avalanche deposits and road‐network vulnerability based on 1986 deposit volumes from 182 paths located in two regions of the French Alps between 2003 and 2017: the Guil and Haute‐Maurienne valleys. During the period, 195 avalanches impacted the road network in these areas, leading to major disruptions. In the Haute‐Maurienne, correlations between deposit volumes and meteorological and snowpack conditions are high in winter. However, the relationships differ with path elevation and orientation. Results do not show any significant relationship between volumes and meteorological or snowpack conditions for the spring season. Focusing on deposits that disturbed the road network in winter and spring reveals a distinct influence of meteorological and snow variables compared to the overall dataset, with snowfall intensity as the predominant control variable of deposit volumes leading to road cuts. When the same analysis is conducted by considering Guil valley separately or by aggregating the Haute‐Maurienne with Guil valley area data, results do not show any significant relationship, highlighting the specific local nature of relations between deposit volumes and meteorological and snowpack conditions.

Signs of Electro-cortical Disconnection revealed by Hd-EEG in Acute Stroke Patients: a Case Study. (P10-1.010)

<h3>Objective:</h3> To assess electro-cortical disconnection induced by stroke lesions in two patients with Hd-EEG study. <h3>Background:</h3> There are overwhelming evidences that stroke lesions induce local and remote effects beyond the site of the primary anatomical damage. These networks effects have been studied mainly via neuroimaging techniques. However, little is known about the electrocortical disconnection caused by acute stroke. Moreover, the spatial resolution has been limited by the adoption of standard EEG. <h3>Design/Methods:</h3> 128 channels Hd-EEG was recorded in two acute stroke patients (Patient 1 and Patient 2) in awake state. Patient 1 presented with aphasia and neglect in ischemic stroke involving left insula, temporal and parietal lobe. Patient 2 had mild left side paresis with evidence of extensive hypoperfusion and small multiple ischemic infarcts in right ICA occlusion. Raw data were pre-processed in MATLAB using AMICA in EEGLAB. Power spectra analysis was performed on delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz) and beta (12–25 Hz) frequencies at whole-brain level and within each hemisphere. Values were then compared between the two hemispheres (lesioned vs not lesioned) using a t-test analysis (p&lt;0.05). <h3>Results:</h3> Patient 1 had not only higher delta and theta power over temporo-parietal and posterior frontal regions but also absence of alpha power over posterior occipital regions. In addition to high delta and theta activity over a broad region including frontal and temporoparietal areas in the hypo-perfused hemisphere, Hd-EEG in Patient 2 showed abnormal delta activity over contralateral frontal regions. <h3>Conclusions:</h3> Our findings point to the presence of electro-cortical disconnection that extends the focal lesion borders. Both patients had either delta activity or loss of alpha power in regions distant from the location of the primary local damage/hypoperfusion that was characterized by slowing. Hd-EEG may reveal network disruption in acute stroke patients in a novel and complementary way compared to neuroimaging. <b>Disclosure:</b> Dr. Monai has nothing to disclose. Miss Sevak has nothing to disclose. The institution of Dr. GJINI has received research support from NIH. The institution of Dr. Struck has received research support from Ceribell. Dr. Boly has nothing to disclose.

937 Disruption of the innate lymphoid cell network alters the hair cycle during induced anagen

937 Disruption of the innate lymphoid cell network alters the hair cycle during induced anagen

Valvular Cardiomyopathy in Aortic Valve Regurgitation Correlates with Myocardial Fibrosis.

Objective: At the tissue level, disruption of the extracellular matrix network leads to irreversible cardiac fibrosis, which contributes to myocardial dysfunction. At the myocyte level, downregulation of beta-adrenoceptors (beta-AR) reduces adaptation to increased workload. The aim of our study was to analyse the correlation between myocardial fibrosis and beta-AR sensitivity in patients with aortic valve (AV) disease. Methods: A total of 92 consecutive patients who underwent elective AV surgery between 2017-2019 were included in our study (51 with aortic regurgitation (AR-group); 41 with aortic stenosis (AS-group) and left ventricular (LV) biopsies were obtained intraoperatively. In vitro force contractility testing was performed by measuring beta-AR sensitivity (-log EC50[ISO]). In parallel, a quantitative analysis of myocardial fibrosis burden was performed. Results: Mean age at the time of AV surgery was not statistically different in both groups (AR: 53.3 ± 15.3 years vs. AS: 58.7 ± 17.0 years; p = 0.116). The LV end-diastolic diameter was significantly enlarged in the AR-group when compared to the AS-group (59.4 ± 15.6 vs. 39.7 ± 21.2; p < 0.001). Analysis of beta-AR sensitivity (AR: -6.769 vs. AS: -6.659; p = 0.316) and myocardial fibrosis (AR: 8.9% vs. AS: 11.3%; p = 0.284) showed no significant differences between patients with AS and AR. There was no correlation between myocardial fibrosis and beta-AR sensitivity in the whole study cohort (R = 0.1987; p = 0.100) or in the AS-subgroup (R = 0.009; p = 0.960). However, significant correlation of fibrosis and beta-AR sensitivity was seen in AR-patients (R = 0.363; p = 0.023). Conclusion: More severe myocardial fibrosis was associated with reduced beta-AR sensitivity in patients presenting with AR but not with AS. Therefore, our results suggest that in patients with AR, cellular myocardial dysfunction is present and correlates with the extent of myocardial fibrosis in the myocardium.

Extreme Weather Events: The Impact of Flooding on Transportation Network: Case Study of Buyukcekmece Basin

Transportation is a critical sector which is vulnerable to hazardous events like urban floods. Thedisruption in transportation infrastructure affects the whole community in terms of loss of life and property.A resilient transport system is fundamental for resilient communities, and considering the adverse impactsof climate change, it becomes even more important. The Büyükçekmece Basin is a densely populated andeconomically significant area that also includes regions of natural importance requiring preservation. Thus,a flood hazard can affect more people, cause greater monetary losses and have negative impact on theenvironment and nature.The purpose of this research is to present the disruption of road network in Büyükçekmece Basin due toflooding and create an analytical framework. Vulnerability of road systems to rainfall-induced floods isquantified by integrating different models. An integrated framework linking hydrological model andinundation model is established and the relation between flood depth and road network vulnerability isdetermined. Flood hazard maps are created for two different rainfall events with 1 in 50 year and 1 in 100-year return period and flooded road lengths are determined. The flood levels have shown that there are roadsegments that will face moderate and major flooding. In Büyükçekmece Basin where serious floods haveoccurred in the past, measures need to be taken regarding the road network for possible flood risks.

Altered brain networks and connections in chronic heart failure patients complicated with cognitive impairment.

Accumulating evidence shows that cognitive impairment (CI) in chronic heart failure (CHF) patients is related to brain network dysfunction. This study investigated brain network structure and rich-club organization in chronic heart failure patients with cognitive impairment based on graph analysis of diffusion tensor imaging data. The brain structure networks of 30 CHF patients without CI and 30 CHF patients with CI were constructed. Using graph theory analysis and rich-club analysis, changes in global and local characteristics of the subjects' brain network and rich-club organization were quantitatively calculated, and the correlation with cognitive function was analyzed. Compared to the CHF patients in the group without CI group, the CHF patients in the group with CI group had lower global efficiency, local efficiency, clustering coefficient, the small-world attribute, and increased shortest path length. The CHF patients with CI group showed lower nodal degree centrality in the fusiform gyrus on the right (FFG.R) and nodal efficiency in the orbital superior frontal gyrus on the left (ORB sup. L), the orbital inferior frontal gyrus on the left (ORB inf. L), and the posterior cingulate gyrus on the right (PCG.R) compared with CHF patients without CI group. The CHF patients with CI group showed a smaller fiber number of edges in specific regions. In CHF patients with CI, global efficiency, local efficiency and the connected edge of the orbital superior frontal gyrus on the right (ORB sup. R) to the orbital middle frontal gyrus on the right (ORB mid. R) were positively correlated with Visuospatial/Executive function. The connected edge of the orbital superior frontal gyrus on the right to the orbital inferior frontal gyrus on the right (ORB inf. R) is positively correlated to attention/calculation. Compared with the CHF patients without CI group, the connection strength of feeder connection and local connection in CHF patients with CI group was significantly reduced, although the strength of rich-club connection in CHF patients complicated with CI group was decreased compared with the control, there was no statistical difference. In addition, the rich-club connection strength was related to the orientation (direction force) of the Montreal cognitive assessment (MoCA) scale, and the feeder and local connection strength was related to Visuospatial/Executive function of MoCA scale in the CHF patients with CI. Chronic heart failure patients with CI exhibited lower global and local brain network properties, reduced white matter fiber connectivity, as well as a decreased strength in local and feeder connections in key brain regions. The disrupted brain network characteristics and connectivity was associated with cognitive impairment in CHF patients. Our findings suggest that impaired brain network properties and decreased connectivity, a feature of progressive disruption of brain networks, predict the development of cognitive impairment in patients with chronic heart failure.

Reversible large-scale network disruption correlates with neurocognitive improvement in HIV-associated minor neurocognitive disorder with combined anti-retroviral therapy intensification: a prospective longitudinal resting-state functional magnetic resonance imaging study.

HIV-associated neurocognitive disorder (HAND) affects multiple cognitive domains and currently, the neuropsychological testing is the gold standard to identify these deficits. The aim of this longitudinal 12-month pilot study is to determine the effect of intensified combination antiretroviral therapy (cART) on rs-fMRI in virally suppressed (both in CSF and blood) patients with active HAND (those who have progressive neurocognitive impairment) and correlated with neurocognitive function tests. In this pilot study, we have evaluated sixteen patients with active HAND with viral suppression in both blood and CSF to study the effect of cART on functional connectivity. Participants underwent rs-fMRI at the baseline (time point-1 (TP-1) and 12-month visits (time point-2 (TP-2)). Connectivity in the five major networks was measured at TP-1 and TP-2 using the seed-based approach. All the participants underwent a five-domain neuropsychological battery at TP-1 and TP-2. Neurocognitive scores (NC) as well as blood and CSF markers were correlated with functional connectivity (FC). There was a significant increase in the FC between the two time points within the executive, salience, default mode, dorsal attention, and visual networks at voxel level threshold of p < 0.001 and cluster level threshold of p < 0.05 and corrected for false detection rate (FDR). The neurocognitive scores were positively correlated with all the networks at similar cluster and voxel level thresholds. These results indicate that rs-fMRI can be potentially used as one of the biomarkers for treatment efficacy in HAND.