Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study

Multiple system atrophy; Neurofilament protein; Parkinsonian disordersAtròfia de sistemes múltiples; Proteïna del neurofilament; Trastorns de ParkinsonAtrofia multisistémica; Proteína de neurofilamento; Trastornos parkinsonianosObjectives: To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates. Methodology: We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD). Results: MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD. Conclusion: Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP

Short-Term Changes in Algometry, Inclinometry, Stabilometry, and Urinary pH Analysis After a Thoracolumbar Junction Manipulation in Patients with Kidney Stones

Objectives: To determine the efficacy of a high-velocity low-amplitude manipulation of the thoracolumbar junction in different urologic and musculoskeletal parameters in subjects suffering from renal lithiasis. Design: Randomized, controlled blinded clinical study. Settings/Location: The Nephrology departments of two hospitals and one private consultancy of physiotherapy in Valencia (Spain). Subjects: Forty-six patients suffering from renal lithiasis. Interventions: The experimental group (EG, n¿=¿23) received a spinal manipulation of the thoracolumbar junction, and the control group (CG, n¿=¿23) received a sham procedure. Outcome measures: Pressure pain thresholds (PPTs) of both quadratus lumborum and spinous processes from T10 to L1, lumbar flexion range of motion, stabilometry, and urinary pH were measured before and immediately after the intervention. A comparison between pre- and postintervention phases was performed and an analysis of variance for repeated measures using time (pre- and postintervention) as intrasubject variable and group (CG or EG) as intersubject variable. Results: Intragroup comparison showed a significant improvement for the EG in the lumbar flexion range of motion (p¿<¿0.001) and in all the PPT (p¿<¿0.001 in all cases). Between-group comparison showed significant changes in PPT in quadratus lumborum (p¿<¿0.001), as well as in the spinous processes of all of the evaluated levels (p¿<¿0.05). No changes in urinary pH were observed (p¿=¿0.419). Conclusion: Spinal manipulation of the thoracolumbar junction seems to be effective in short term to improve pain sensitivity, as well as to increase the lumbar spine flexion

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

A novel investigation into the application of non-destructive evaluation for vibration assessment and analysis of in-service pipes

Flow induced vibrations that are close to resonance frequencies are a major problem in all oil and gas processing industries, so all piping systems require regular condition monitoring and inspection to assess changes in their dynamic characteristics and structural integrity in order to prevent catastrophic failures. One of the main causes of pipe failure is weak support causing low frequency high amplitude flow-induced vibration. This causes wear and tear, especially near joints due to their dissimilar stiffness resulting in fatigue failure of joints caused by vibration-induced high cyclic stress. Other contributing factors in pipe failure are poor or inadequate design, poor workmanship during installation or maintenance and inadequate or weak and flexible support. These pipes are usually required to work non-stop for 24 hours a day 7 days a week for weeks, months or years at a time. Regular monitoring and in-service dynamic analysis should ensure continuous and safe operation. A novel method of non-destructive testing and evaluation of these pipes, while in service, is proposed in this paper. This technique will enable early detection and identification of the root causes of any impending failure due to excess vibration as a result of cyclic force induced by the flow. The method pinpoints the location of the impending failure prior to condition-based maintenance procedures. The technique relies on the combined application of Operating Deflection Shapes (ODS) analysis and computational mechanics utilizing Finite Element Analysis (FEA), i.e. linear elastic stress analysis. Any structural modification to the pipes and their supports can then be applied virtually and their effects on the system can be analysed. The effect on vibration levels is assessed and verified. The effect of any change in the forces corresponding to changes in the Differential Pressure (DP) at constant flow rate through the pipes can then be estimated. It was concluded that maintaining the differential pressure above some “critical” threshold ensures the pipe operates under the allowable dynamic stress for a theoretically “indefinite” life cycle

Intramuscular EMG-driven musculoskeletal modelling: towards implanted muscle interfacing in spinal cord injury patients

OBJECTIVE: Surface EMG-driven modelling has been proposed as a means to control assistive devices by estimating joint torques. Implanted EMG sensors have several advantages over wearable sensors but provide a more localized information on muscle activity, which may impact torque estimates. Here, we tested and compared the use of surface and intramuscular EMG measurements for the estimation of required assistive joint torques using EMG driven modelling. METHODS: Four healthy subjects and three incomplete spinal cord injury (SCI) patients performed walking trials at varying speeds. Motion capture marker trajectories, surface and intramuscular EMG, and ground reaction forces were measured concurrently. Subject-specific musculoskeletal models were developed for all subjects, and inverse dynamics analysis was performed for all individual trials. EMG-driven modelling based joint torque estimates were obtained from surface and intramuscular EMG. RESULTS: The correlation between the experimental and predicted joint torques was similar when using intramuscular or surface EMG as input to the EMG-driven modelling estimator in both healthy individuals and patients. CONCLUSION: We have provided the first comparison of non-invasive and implanted EMG sensors as input signals for torque estimates in healthy individuals and SCI patients. SIGNIFICANCE: Implanted EMG sensors have the potential to be used as a reliable input for assistive exoskeleton joint torque actuation

Inferring introduction routes of invasive species using approximate Bayesian computation on microsatellite data

Determining the routes of introduction provides not only information about the history of an invasion process, but also information about the origin and construction of the genetic composition of the invading population. It remains difficult, however, to infer introduction routes from molecular data because of a lack of appropriate methods. We evaluate here the use of an approximate Bayesian computation (ABC) method for estimating the probabilities of introduction routes of invasive populations based on microsatellite data. We considered the crucial case of a single source population from which two invasive populations originated either serially from a single introduction event or from two independent introduction events. Using simulated datasets, we found that the method gave correct inferences and was robust to many erroneous beliefs. The method was also more efficient than traditional methods based on raw values of statistics such as assignment likelihood or pairwise F(ST). We illustrate some of the features of our ABC method, using real microsatellite datasets obtained for invasive populations of the western corn rootworm, Diabrotica virgifera virgifera. Most computations were performed with the DIYABC program (http://www1.montpellier.inra.fr/CBGP/diyabc/)

Spleen Tyrosine Kinase (Syk) Regulates Systemic Lupus Erythematosus (SLE) T Cell Signaling

Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients

Moral enhancement: do means matter morally?

One of the reasons why moral enhancement may be controversial, is because the advantages of moral enhancement may fall upon society rather than on those who are enhanced. If directed at individuals with certain counter-moral traits it may have direct societal benefits by lowering immoral behavior and increasing public safety, but it is not directly clear if this also benefits the individual in question. In this paper, we will discuss what we consider to be moral enhancement, how different means may be used to achieve it and whether the means we employ to reach moral enhancement matter morally. Are certain means to achieve moral enhancement wrong in themselves? Are certain means to achieve moral enhancement better than others, and if so, why? More specifically, we will investigate whether the difference between direct and indirect moral enhancement matters morally. Is it the case that indirect means are morally preferable to direct means of moral enhancement and can we indeed pinpoint relevant intrinsic, moral differences between both? We argue that the distinction between direct and indirect means is indeed morally relevant, but only insofar as it tracks an underlying distinction between active and passive interventions. Although passive interventions can be ethical provided specific safeguards are put in place, these interventions exhibit a greater potential to compromise autonomy and disrupt identity