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Up to 25% of children experience sleep problems. Transactional sleep models suggest bidirectional associations between parenting and children’s sleep problems. The current study aims to clarify the temporal associations between maternal sensitivity and children’s sleep problems across early childhood. This study includes 942 mother-child dyads from the Generation R Study, a population-based prospective cohort. Observed maternal sensitivity was coded using the Ainsworth’s rating scales (child age 1.5 years) and the revised Erickson rating scales (child ages 3 and 4 years). Caregivers reported children’s sleep problems on the Child Behavior Checklist at child ages 1.5, 3, and 6 years. Cross-lagged panel modelling showed that higher levels of maternal sensitivity at child age 3 years were associated with fewer sleep problems at child age 6 years; no other associations were found. Findings of the current study indicate an association of parenting with children’s sleep across early childhood, no evidence was found for a bidirectional association.

The mechanical dehydration method is generally used for reducing the moisture content in sludge. However, there is little understanding of the physical and mechanical properties and dehydration mechanism of sludge during pressurization. In this paper, characteristics of sludge were studied from the perspective of soil mechanics. The water permeability, loading conditions, and dehydration performance of the sludge during the pressurization process were analyzed through a series of geotechnical laboratory experiments. The results showed that the pore structure, compressibility coefficient, consolidation coefficient, and permeability coefficient of the sludge are related to the dehydration rate. The conditioners that mixed with sludge could increase the dewatering rate by reducing the sludge viscosity, changing the water status, and increasing the permeability coefficient. The two conditioners used in this study increased the dehydration rate of the sludge from 27.5 to 52.6% and 63.9%, respectively. Unlike the seepage consolidation of ordinary clay, which has only one stage, the seepage consolidation of sludge could be divided into three stages. The removed water in the first stage is mainly free water; the discharge in the second stage is the combination of free water and bound water, and bound water was mainly discharged in the third stage. The water content at the end of each stage corresponds to the liquid limit, plastic limit, and shrinkage limit of the sludge. Our study provides a novel insight for understanding the deep dewatering of sludge and is benefit to solve the problem of sludge dewatering.

Breast cancer (BC) is the most common cancer among women in Hong Kong. The Food and Health Bureau commissioned The University of Hong Kong (HKU) to conduct the Hong Kong Breast Cancer Study (HKBCS) with the aim of identifying relevant risk factors for BC in Hong Kong and developing a locally validated BC risk assessment tool for Hong Kong Chinese women. After consideration of the most recent international and local scientific evidence including findings of the HKBCS, the Cancer Expert Working Group on Cancer Prevention and Screening (CEWG) has reviewed and updated its BC screening recommendations. Existing recommendations were preserved for women at high risk and slightly changed for women at moderate risk. The following major updates have been made concerning recommendations for other women in the general population: Women aged 44 to 69 with certain combinations of personalised risk factors (including presence of history of BC among first-degree relative, a prior diagnosis of benign breast disease, nulliparity and late age of first live birth, early age of menarche, high body mass index and physical inactivity) putting them at increased risk of BC are recommended to consider mammography screening every 2 years. They should discuss with their doctors on the potential benefits and harms before undergoing mammography screening. A risk assessment tool for local women (eg, one developed by HKU) is recommended to be used for estimating the risk of developing BC with regard to the personalised risk factors described above.

Background : Scoliosis is a health problem that causes a side-to-side curvature in the spine. The curvature may have an “S” or “C” shape. To evaluate scoliosis, the Cobb angle has been commonly used. However, digital image processing allows the Cobb angle to be obtained easily and quickly, several researchers have determined that Cobb angle contains high variations (errors) in the measurements. Therefore, a more reproducible computer aided-method to evaluate scoliosis is presented. Material and Methods: In this analytical study, several polynomial curves were fitted to the spine curvature (4 th to 8 th order) of thirty plain films of scoliosis patients to obtain the Curvature-Length of the spine. Each plain film was evaluated by 3 physician observers. Curvature was measured twice using the Cobb method and the proposed Curvature-Length Technique (CLT). Data were analyzed by a paired-sample Student t-test and Pearson correlation method using SPSS Statistics 25. Results: The curve of 7 th order polynomial had the best fit on the spine curvature and was also used for our proposed method (CLT) obtaining a significant positive correlation when compared to Cobb measurements (r=0.863, P

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Genetic signatures caused by demographic and adaptive processes during past climatic shifts can inform predictions of species’ responses to anthropogenic climate change. To identify these signatures in Acropora tenuis, a reef-building coral threatened by global warming, we first assembled the genome from long reads and then used shallow whole-genome resequencing of 150 colonies from the central inshore Great Barrier Reef to inform population genomic analyses. We identify population structure in the host that reflects a Pleistocene split, whereas photosymbiont differences between reefs most likely reflect contemporary (Holocene) conditions. Signatures of selection in the host were associated with genes linked to diverse processes including osmotic regulation, skeletal development, and the establishment and maintenance of symbiosis. Our results suggest that adaptation to post-glacial climate change in A. tenuis has involved selection on many genes, while differences in symbiont specificity between reefs appear to be unrelated to host population structure.

To explore the application effect of nursing intervention guided by King’s interactive standard theory in patients with lumbar disc herniation undergoing conservative treatment. Total of 136 patients with lumbar disc herniation admitted to our hospital from June 2019 to May 2020 were randomly divided into interactive nursing group and routine nursing group. The interactive nursing group was given nursing intervention guided by King’s interactive standard theory and the routine nursing group was given routine nursing guidance. The disease cognition rate, incidence of adverse behavior, lumbar function and pain degree were compared between the two groups. The disease cognition rates of main symptoms, disease type, familiarity with conservative treatment, necessity of hard bed rest, feasible surgical treatment in severe cases and causes of disease in interactive nursing group were higher than those in routine nursing group (p

Background Elective total knee replacement (TKR) is a safe and cost-effective surgical procedure for treating severe knee osteoarthritis (OA). Although complications following surgery are rare, prediction tools could help identify those patients who are at particularly high risk who could then be targeted with preventative interventions. We aimed to develop a simple model to help inform treatment choices. Methods We trained and externally validated adverse event prediction models for patients with TKR using electronic health records (EHR) and claims data from the US (OPTUM, CCAE, MDCR, and MDCD) and general practice data in the UK (IQVIA Medical Research Database ([IMRD], incorporating data from The Health Improvement Network [THIN], a Cegedim database). The target population consisted of patients undergoing a primary TKR, aged ≥40 years and registered in any of the contributing data sources for ≥1 year before surgery. LASSO logistic regression models were developed for four adverse outcomes: post-operative (90-day) mortality, venous thromboembolism (VTE), readmission, and long-term (5-year) revision surgery. A second model was developed with a reduced feature set to increase interpretability and usability. Findings A total of 508,082 patients were included, with sample size per data source ranging from 1,853 to 158,549 patients. Overall, 90-day mortality, VTE, and readmission prevalence occurred in a range of 0.20%-0.32%, 1.7%-3.0% and 2.2%-4.8%, respectively. Five-year revision surgery was observed in 1.5%-3.1% of patients. The full model predicting 90-day mortality yielded AUROC of 0.78 when trained in OPTUM and yielded an AUROC of 0.70 when externally validated on THIN. We then developed a 12 variable model which achieved internal AUROC of 0.77 and external AUROC of 0.71 in THIN. The discriminative performances of the models predicting 90-day VTE, readmission, and 5-year revision were consistently poor across the datasets (AUROC Interpretation We developed and externally validated a simple prediction model based on sex, age, and 10 comorbidities that can identify patients at high risk of short-term mortality following TKR. Our model had a greater discriminative ability than the Charlson Comorbidity Index in predicting 90-day mortality. The 12-feature mortality model is easily implemented and the performance suggests it could be used to inform evidence based shared decision-making prior to surgery and for appropriate precautions to be taken for those at high risk. The other outcomes examined had low performance. Funding This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The sponsor of the study did not have any involvement in the writing of the manuscript or the decision to submit it for publication. The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). DPA is funded by a National Institute for Health Research Clinician Scientist award (CS-2013-13-012). TDS is funded by the Department of Health of the Generalitat de Catalunya under the Strategic Plan for Research and Innovation in Health (PERIS; SLT002/16/00308). The views expressed in this publication are those of the authors and not those of the NHS, the National Institute for Health Research or the Department of Health. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Key Points Question Is it possible to predict adverse events following total knee replacement? Findings Mortality was the only adverse event studied that we were able to predict with adequate performance. We produced a 12 variable prediction model for 90-day post-operative mortality that achieved an AUROC of 0.77 on internal test validation (Optum) and 0.71 when externally validated in THIN. The model also showed adequate calibration. Meaning Patients can now be presented with an accurate risk assessment for short term mortality such that they are well-informed before the decision for surgery is taken. Importance Total Knee Replacement is generally a safe, effective procedure that is performed on thousands of patients each year. However, a small number of those patients will experience adverse events. Due to the surgery’s elective nature, a well calibrated, high performing risk model could pre-emptively inform the patient and clinician decision making process and help to guide preventative treatment.

Background Dysphagia is a common symptom and may be a cause of death in patients with spinocerebellar ataxias (SCAs). However, little is known about at which disease stage dysphagia becomes clinically relevant. Therefore, our study aims to investigate the prevalence of dysphagia in different disease stages of SCA 1, 2, 3 and 6. Methods We studied 237 genetically confirmed patients with SCA 1, 2, 3, 6 from the Clinical Research Consortium for SCAs and investigated the prevalence of self-reported dysphagia and the association between dysphagia and other clinical characteristics. We further stratified ataxia severity and studied the prevalence of dysphagia at each disease stage. Results Dysphagia was present in 59.9% of SCA patients. Patients with dysphagia had a longer disease duration and more severe ataxia than patients without dysphagia (patients with dysphagia vs. without dysphagia, disease duration (years): 14.51 ± 8.91 vs. 11.22 ± 7.82, p = .001, scale for the assessment and rating of ataxia [SARA]: 17.90 ± 7.74 vs. 13.04 ± 7.51, p = .000). Dysphagia was most common in SCA1, followed by SCA3, SCA 6, and SCA 2. Dysphagia in SCA1 and 3 was associated robustly with ataxia severity, whereas this association was less obvious in SCA2 and 6, demonstrating genotype-specific clinical variation. Conclusion Dysphagia is a common clinical symptom in SCAs, especially in the severe disease stage. Understanding dysphagia in SCA patients can improve the care of these patients and advance knowledge on the roles of the cerebellum and brainstem control in swallowing.

To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments. 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1–2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments. There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1–3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1–3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups. DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

We examined the expression of vascular endothelial growth factor (VEGF) and characteristics of human neural stem cells after transfection with the lentiviral vector encoding the VEGF 165 gene. The latter gene was amplified from the human breast cancer cell line MCF-7 using RT-PCR; then the target gene was cloned into the pCDH–CMV–MCS-EF1-copGFP, a lentiviral expressing plasmid. After transformation, enzyme digestion led to a correct length of the VEGF165 gene, and DNA sequencing analysis confirmed that the VEGF165 gene sequence was exactly the same as that reported by the GeneBank. Then, the recombinant lentivirus produced by 293T cells and packaging plasmids were transfected into fourthpassage human neural stem cells (NSCs). One week after transfection with pCDH-VEGF165, NSCs expressed VEGF stably, and their proliferation ability significantly increased. Furthermore, human NSCs kept their characteristics and multiple differentiation activity after transfection. Our results indicate that human NSCs can express vascular endothelial growth factor highly and stably via transfection with the lentiviral vector encoding the VEGF165 gene, which may be useful for future research on function recovery after stroke.

To investigate the biologic viability and boundary range of hepatic alveolar echinococcosis (HAE) by the contrast-enhanced ultrasonography (CEUS) and acoustic radiation force impulse elastography (ARFI).Totally 27 HAE patients confirmed by pathology underwent CEUS and ARFI examinations.Gray scale sonography of HAE showed unclear boundary, inhomogeneous, and middle hyperechoic nodules, and the maximum area was (6.08 ± 4.47) cmCEUS and ARFI examinations can detect the biologic viability and boundary range of migrating zone around HAE, which is valuable for guiding treatment, judging curative effect, and predicting prognosis.

Background For a variety of sporadic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, it is well-established that ethnicity does affect the disease phenotypes. However, how ethnicity contributes to the clinical symptoms and disease progressions in monogenetic disorders, such as spinocerebellar ataxia type 3 (SCA3), remains less studied. Methods We used multivariable linear and logistical regression models in 257 molecularly-confirmed SCA3 patients (66 Caucasians, 43 African Americans, and 148 Asians [composed of 131 Chinese and 17 Asian Americans]) to explore the influence of ethnicity on age at onset (AAO), ataxia severity, and non-ataxia symptoms (i.e. depression, tremor, and dystonia). Results We found that Asians had significantly later AAO, compared to Caucasians (β = 4.75, p = 0.000) and to African Americans (β = 6.64, p = 0.000) after adjusting for the pathological CAG repeat numbers in ATXN3. African Americans exhibited the most severe ataxia as compared to Caucasians (β = 3.81, p = 0.004) and Asians (β = 4.39, p = 0.001) after taking into consideration of the pathological CAG repeat numbers in ATXN3 and disease duration. Caucasians had a higher prevalence of depression than African Americans (β = 1.23, p = 0.040). Ethnicity had no influence on tremor or dystonia. Conclusions Ethnicity plays an important role in clinical presentations of SCA3 patients, which could merit further clinical studies and public health consideration. These results highlight the role of ethnicity in monogenetic, neurodegenerative disorders.

Introduction Pulmonary arterial hypertension (PAH) is characterised by vascular remodelling of pulmonary arterioles. Disrupted iron homeostasis linked to elevated hepcidin levels has been observed in PAH patients, and disruption of the hepcidin/ferroportin axis at the level of the pulmonary vasculature cells has been shown to contribute to proliferation of pulmonary artery smooth muscle cells. A role for Pulmonary artery endothelial cells (PAECs) linked to hepcidin has not been investigated. Objectives In this study we explored the influences of hepcidin-25 on PAEC gene expression targeting BMPRII, known to be dysfunctional in PAH. Methods Cells were challenged with Hepcidin-25 (1 μg/mL) or for comparison IL-6 (10 ng/mL). Transcriptional regulation was analysed by RT-PCR, protein expression by immunocytochemistry. Results Novel findings demonstrate that BMPRII mRNA expression is significantly down regulated in PAECs challenged with hepcidin-25 over a time course from 1 hour to 5 hours; figure 1 illustrates findings at 3 hours. IL-6 challenge was not able to replicate this response over the same time frame. In addition, Western blot analysis of cell lysates (n=2) showed an obvious loss of BMPRII protein expression in Hepcidin-25 challenged cells when compared to control and IL-6 challenged cell lysates. Conclusion This is the first report linking hepcidin-25 activity to potentially dysfunctional BMPRII responses in PAECs. Given the established role of hepcidin as regulator of cellular iron levels, a role for downstream signaling linked to iron accumulation in PAECs may offer a plausible mechanism for these observations and warrants further investigation. These studies may provide novel insights regarding emerging concepts of hepcidin driven proliferative and second messenger responses of relevance to PAH.

Objective The aim of this study is to evaluate the correlation between resting state functional MRI (RS-fMRI) activity and motor and cognitive impairment in spinocerebellar ataxia type 6 (SCA6). Methods Twelve patients with genetically confirmed SCA6 and 14 age matched healthy controls were imaged with RS-fMRI. Whole brain gray matter was automatically parcellated into 1000 regions of interest (ROIs). For each ROI, the first eigenvariate of voxel time courses was extracted. For each patient, Pearson correlation coefficients between each pair of ROI time courses were calculated across the 1000 ROIs. The set of average control correlation coefficients were fed as an undirected weighted adjacency matrix into the Rubinov and Sporns (2010) modularity algorithm. The intranetwork global efficiency of the thresholded adjacency sub-matrix was calculated and correlated with ataxia scores and cognitive performance. Results SCA6 patients showed mild cognitive impairments in executive function and visual-motor processing compared to control subjects. These neuropsychological impairments were correlated with decreased RS functional connectivity (FC) in the attention network. Conclusions Mild cognitive executive functions and visual-motor coordination impairments seen in SCA6 patients correlate with decreased resting-state connectivity in the attention network, suggesting a possible metric for the study of cognitive dysfunction in cerebellar disease. Hum Brain Mapp 38:3001–3010, 2017. © 2017 Wiley Periodicals, Inc.

BACKGROUND: Cerebellar degenerative pathology has been identified in tremor patients; however, how the degenerative pathology could contribute to tremor remains unclear. If the cerebellar degenerative pathology can directly drive tremor, one would hypothesize that tremor is likely to occur in the diseases of cerebellar ataxia and follows the disease progression in such disorders. METHODS: To further test this hypothesis, we studied the occurrence of tremor in different disease stages of classical cerebellar degenerative disorders: spinocerebellar ataxias (SCAs). We further separately analyzed postural tremor and rest tremor, two forms of tremor that both involve the cerebellum. We also explored tremor in different subtypes of SCAs. RESULTS: We found that 18.1% of SCA patients have tremor. Interestingly, SCA patients with tremor have worse ataxia than those without tremor. When stratifying patients into mild, moderate, and severe disease stages according to the severity of ataxia, moderate and severe SCA patients more commonly have tremor than those with mild ataxia, the effect most prominently observed in postural tremor of SCA3 and SCA6 patients. Finally, tremor can independently contribute to worse functional status in SCA2 patients, even after adjusting for ataxia severity. CONCLUSIONS: Tremor is more likely to occur in the severe stage of cerebellar degeneration when compared to mild stages. Our results partially support the cerebellar degenerative model of tremor.

To better understand cerebellum-related diseases and functional mapping of the cerebellum, quantitative measurements of cerebellar regions in magnetic resonance (MR) images have been studied in both clinical and neurological studies. Such studies have revealed that different spinocerebellar ataxia (SCA) subtypes have different patterns of cerebellar atrophy and that atrophy of different cerebellar regions is correlated with specific functional losses. Previous methods to automatically parcellate the cerebellum-that is, to identify its sub-regions-have been largely based on multi-atlas segmentation. Recently, deep convolutional neural network (CNN) algorithms have been shown to have high speed and accuracy in cerebral sub-cortical structure segmentation from MR images. In this work, two three-dimensional CNNs were used to parcellate the cerebellum into 28 regions. First, a locating network was used to predict a bounding box around the cerebellum. Second, a parcellating network was used to parcellate the cerebellum using the entire region within the bounding box. A leave-one-out cross validation of fifteen manually delineated images was performed. Compared with a previously reported state-of-the-art algorithm, the proposed algorithm shows superior Dice coefficients. The proposed algorithm was further applied to three MR images of a healthy subject and subjects with SCA6 and SCA8, respectively. A Singularity container of this algorithm is publicly available.

The fatty acyl delta-6 desaturase (Δ6-desaturase) is a key rate-limiting enzyme in the biosynthesis of long-chain polyunsaturated fatty acids (LCPUFAs). To study the effects of different oil sources in the feed on the nutritional regulation of Δ6-desaturase-like gene mRNA expression, the fulllength cDNA of the Δ6-desaturase-like gene was cloned from the liver of Manchurian trout (Brachymystax lenok). A 9-week feeding trial was performed, and the fish received diets with three different oil sources: fish oil (FO), sunflower oil (SO), and linseed oil (LO). The results showed that the 2448 bp long full-length cDNA contained an open reading frame (with a length of 1365 bp), encoding 454 amino acids. Gene expression analysis indicated that Δ6-desaturase-like gene mRNA is widely distributed throughout different tissues, with highest expression levels in both the liver and the brain. The linolenic acid (ALA) and linoleic acid (LA) compositions were highest in LO and SO diets, respectively. The eicosapentaenoic acid and docosahexaenoioc acid composition in LO and SO diets were significantly lower than in the FO diet. Fish fed with SO and LO showed significantly higher liver expression levels of Δ6-desaturase-like gene mRNA than those fed with FO. This indicates that SO and LO in the diet affected the nutritional regulation of the Δ6-desaturase-like gene mRNA in the liver of the Manchurian trout. In addition, these data suggest that the Manchurian trout has the ability to synthesize long-chain unsaturated fatty acids (LC-PUFAs) from ALA and LA.

[EN] The human cerebellum plays an essential role in motor control, is involved in cognitive function (i.e., attention, working memory, and language), and helps to regulate emotional responses. Quantitative in-vivo assessment of the cerebellum is important in the study of several neurological diseases including cerebellar ataxia, autism, and schizophrenia. Different structural subdivisions of the cerebellum have been shown to correlate with differing pathologies. To further understand these pathologies, it is helpful to automatically parcellate the cerebellum at the highest fidelity possible. In this paper, we coordinated with colleagues around the world to evaluate automated cerebellum parcellation algorithms on two clinical cohorts showing that the cerebellum can be parcellated to a high accuracy by newer methods. We characterize these various methods at four hierarchical levels: coarse (i.e., whole cerebellum and gross structures), lobe, subdivisions of the vermis, and the lobules. Due to the number of labels, the hierarchy of labels, the number of algorithms, and the two cohorts, we have restricted our analyses to the Dice measure of overlap. Under these conditions, machine learning based methods provide a collection of strategies that are efficient and deliver parcellations of a high standard across both cohorts, surpassing previous work in the area. In conjunction with the rank-sum computation, we identified an overall winning method., The data collection and labeling of the cerebellum was supported in part by the NIH/NINDS grant R01 NS056307 (PI: J.L. Prince) and NIH/NIMH grants R01 MH078160 & R01 MH085328 (PI: S.H. Mostofsky). PMT is supported in part by the NIH/NIBIB grant U54 EB020403. CERES2 development was supported by grant UPV2016-0099 from the Universitat Politecnica de Valencia (PI: J.V. Manjon); the French National Research Agency through the Investments for the future Program IdEx Bordeaux (ANR-10-IDEX-03-02, HL-MRI Project; PI: P. Coupe) and Cluster of excellence CPU and TRAIL (HR-DTI ANR-10-LABX-57; PI: P. Coupe). Support for the development of LiviaNET was provided by the National Science and Engineering Research Council of Canada (NSERC), discovery grant program, and by the ETS Research Chair on Artificial Intelligence in Medical Imaging. The authors wish to acknowledge the invaluable contributions offered by Dr. George Fein (Dept. of Medicine and Psychology, University of Hawaii) in preparing this manuscript.

Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110δ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110δ on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110δ activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110δ pharmacologic inactivation is effective when initiated after transplantation. Targeting p110δ activity might be a viable strategy for the treatment of heart chronic rejection in humans.

This research presents a novel low-cost pedagogical environment oriented to ease the use experiential learning methods for training on image-guided robotic surgery technologies. The environment proposes a simplified surgical simulation use case: the movement of insertion and extraction of a needle, similar to an image-guided biopsy situation. The training environment is composed of a 3D-printed phantom, a CT scan of the phantom, a virtual reality environment that includes haptic information, an ad-hoc 1 degree of freedom (DOF) robotic system for insertion/extraction and a Novint Falcon, a low cost 3 DOF manipulator that allows achieving haptic feedback. A first pilot experience has been carried out in the ?Surgical Simulation and Planning? course of the Bachelor of Biomedical Engineering at Universidad Politécnica de Madrid (UPM). Results of the surveys carried out (by teachers and learners) show that the new project-based methodology improves in all cases the values of student?s satisfaction obtained using the classical methodology based on master classes and practices.

The cerebellar peduncles, comprising the superior cerebellar peduncles (SCPs), the middle cerebellar peduncle (MCP), and the inferior cerebellar peduncles (ICPs), are white matter tracts that connect the cerebellum to other parts of the central nervous system. Methods for automatic segmentation and quantification of the cerebellar peduncles are needed for objectively and efficiently studying their structure and function. Diffusion tensor imaging (DTI) provides key information to support this goal, but it remains challenging because the tensors change dramatically in the decussation of the SCPs (dSCP), the region where the SCPs cross. This paper presents an automatic method for segmenting the cerebellar peduncles, including the dSCP. The method uses volumetric segmentation concepts based on extracted DTI features. The dSCP and noncrossing portions of the peduncles are modeled as separate objects, and are initially classified using a random forest classifier together with the DTI features. To obtain geometrically correct results, a multi-object geometric deformable model is used to refine the random forest classification. The method was evaluated using a leave-one-out cross-validation on five control subjects and four patients with spinocerebellar ataxia type 6 (SCA6). It was then used to evaluate group differences in the peduncles in a population of 32 controls and 11 SCA6 patients. In the SCA6 group, we have observed significant decreases in the volumes of the dSCP and the ICPs and significant increases in the mean diffusivity in the noncrossing SCPs, the MCP, and the ICPs. These results are consistent with a degeneration of the cerebellar peduncles in SCA6 patients.

Ocular motor abnormalities reflect the varied neuropathology of spinocerebellar ataxias (SCAs) and may serve to clinically distinguish the different SCAs. We analyzed the various eye movement abnormalities detected prospectively at the baseline visit during a large multicenter natural history study of SCAs 1, 2, 3, and 6.The data were prospectively collected from 12 centers in the United States in patients with SCAs 1, 2, 3, and 6, as part of the Clinical Research Consortium for Spinocerebellar Ataxias (NIH-CRC-SCA). Patient characteristics, ataxia rating scales, the Unified Huntington Disease Rating Scale functional examination, and clinical staging were used. Eye movement abnormalities including nystagmus, disorders of saccades and pursuit, and ophthalmoparesis were recorded, and factors influencing their occurrence were examined.A total of 301 patients participated in this study, including 52 patients with SCA 1, 64 with SCA 2, 117 with SCA 3, and 68 with SCA 6. Although no specific ocular motor abnormality was pathognomonic to any SCA, significant differences were noted in their occurrence among different disorders. SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades. SCA 1 and SCA 3 subjects had a more even distribution of eye movement abnormalities.Prospective data from a large cohort of patients with SCAs 1, 2, 3, and 6 provide statistical validation that the SCAs exhibit distinct eye movement abnormalities that are useful in identifying the genotypes. Many of the abnormalities correlate with greater disease severity measures.

Background Dystonia is a common feature in spinocerebellar ataxias (SCAs). Whether the presence of dystonia is associated with different rate of ataxia progression is not known. Objectives To study clinical characteristics and ataxia progression in SCAs with and without dystonia. Methods We studied 334 participants with SCA 1, 2, 3 and 6 from the Clinical Research Consortium for Spinocerebellar Ataxias (CRC-SCA) and compared the clinical characteristics of SCAs with and without dystonia. We repeatedly measured ataxia progression by the Scale for Assessment and Rating of Ataxia every 6 months for 2 years. Regression models were employed to study the association between dystonia and ataxia progression after adjusting for age, sex and pathological CAG repeats. We used logistic regression to analyze the impact of different repeat expansion genes on dystonia in SCAs. Results Dystonia was most commonly observed in SCA3, followed by SCA2, SCA1, and SCA6. Dystonia was associated with longer CAG repeats in SCA3. The CAG repeat number in TBP normal alleles appeared to modify the presence of dystonia in SCA1. The presence of dystonia was associated with higher SARA scores in SCA1, 2, and 3. Although relatively rare in SCA6, the presence of dystonia was associated with slower progression of ataxia. Conclusions The presence of dystonia is associated with greater severity of ataxia in SCA1, 2, and 3, but predictive of a slower progression in SCA6. Complex genetic interactions among repeat expansion genes can lead to diverse clinical symptoms and progression in SCAs.

The aim of this study is to determine whether the initial symptom associates with motor progression in spinocerebellar ataxias (SCAs). SCAs are clinically heterogeneous and the initial presentation may represent different subtypes of SCA with different motor progression. We studied 317 participants with SCAs1, 2, 3, and 6 from the Clinical Research Consortium for SCAs (CRC-SCA) and repeatedly measured the severity of ataxia for 2 years. SCA patients were divided into gait-onset and non-gait-onset (speech, vision, and hand dexterity) groups based on the initial presentation. In addition to demographic comparison, we employed regression models to study ataxia progression in these two groups after adjusting for age, sex, and pathological CAG repeats. The majority of SCA patients had gait abnormality as an initial presentation. The pathological CAG repeat expansions were similar between the gait-onset and non-gait-onset groups. In SCA1, gait-onset group progressed slower than non-gait-onset group, while gait-onset SCA6 group progressed faster than their counterpart. In addition, the disease presented 9 years later for SCA2 gait-onset group than non-gait-onset group. Initial symptoms of SCA3 did not influence age of onset or disease progression. The initial symptom in each SCA has a different influence on age of onset and motor progression. Therefore, gait and non-gait-onset groups of SCAs might represent different subtypes of the diseases.

The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects’ cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.