Wanted dead or alive? The tradeoff between in-vivo versus ex-vivo MR brain imaging in the mouse

High-resolution MRI of the mouse brain is gaining prominence in estimating changes in neuroanatomy over time to understand both normal developmental as well as disease processes and mechanisms. These types of experiments, where a change in time is to be captured as accurately as possible using imaging, face multiple experimental design choices. Chief amongst these choices is whether to image ex-vivo, where superior resolution and contrast are available, or in-vivo, where resolution and contrast are lower but the animal can be followed longitudinally. Here we explore this tradeoff by first estimating the sources of variability in anatomical mouse MRI and then, using statistical simulations, provide power analyses of these experiment design choices

Home Program of Hip Abductor Exercises: Effect on Knee Joint Loading, Strength, Function and Pain in Persons with Knee Osteoarthritis

Background Hip abductor muscle weakness may result in impaired frontal-plane pelvic control during gait, leading to greater medial compartment loading in people with knee osteoarthritis (OA). Objective This study investigated the effect of an 8-week home strengthening program for the hip abductor muscles on knee joint loading (measured by the external knee adduction moment during gait), strength (force-generating capacity), and function and pain in individuals with medial knee OA. Design The study design was a nonequivalent, pretest-posttest, control group design. Setting Testing was conducted in a motor performance laboratory. Patients An a priori sample size calculation was performed. Forty participants with knee OA were matched for age and sex with a control group of participants without knee OA. Intervention Participants with knee OA completed a home hip abductor strengthening program. Measurements Three-dimensional gait analysis was performed to obtain peak knee adduction moments in the first 50% of the stance phase. Isokinetic concentric strength of the hip abductor muscles was measured using an isokinetic dynamometer. The Five-Times-Sit-to-Stand Test was used to evaluate functional performance. Knee pain was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. Results Following the intervention, the OA group demonstrated significant improvement in hip abductor strength, but not in the knee adduction moment. Functional performance on the sit-to-stand test improved in the OA group compared with the control group. The OA group reported decreased knee pain after the intervention. Limitations Gait strategies that may have affected the knee adduction moment, including lateral trunk lean, were not evaluated in this study. Conclusions Hip abductor strengthening did not reduce knee joint loading but did improve function and reduce pain in a group with medial knee OA

Retinal blood vessels extraction using probabilistic modelling

© 2014 Kaba et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts.The Department of Information Systems, Computing and Mathematics, Brunel University

The Effects of Square-Stepping Exercise on Risk of Falling and Balance in Senior Adults

As people age, their body systems gradually deteriorate. Muscle function and the vestibular system slowly deteriorate leading to lower body instability. Older adults who struggle with dizziness and imbalance are more prone to falling. Dizziness and imbalance cause falls, and falls are the leading cause of hospitalization and accidental death in older adults (Shinichi & Tatsuya, 2015). It is possible to prevent and reduce the risk of falls through balance training. It is crucial that older adults take the steps needed to improve their balance and therefore reduce their risk of falling. PURPOSE: To evaluate the effect of a 10-week Square-Stepping Exercise (SSE) program in older adults using the Biodex balance system. METHODS: Eleven adults over the age of 60 and involved in the Senior Jacket program at Cedarville University participated in this 10-week study (0 males, 11 females; mean age=76). Measurements taken prior to and after the intervention include Activities-specific Balance Confidence (ABC) Scale, Timed-Up-And-Go Test, 30-Second Chair Stand Test, Limits of Stability Test, and Fall Risk Test. A Repeated Measures ANOVA was used to determine changes in initial and final balance testing scores. RESULTS: The study revealed that significant differences were found for the functional fitness tests. SPSS indicated a significant difference in improvement from pretest to posttest for the Timed-Up-and-Go Test (P = .003) as well as the 30-Second Chair Stand Test (P = .043). For the Limits of Stability test, there was no significant change from pretest to posttest for the overall (P =0.162) or any of the 8 directions. The Fall Risk Test score also showed no significant change (P =0.831). The ABC Scale test did not show significant improvement either (P = 0.995). CONCLUSION: Overall, the results showed that the participants significantly benefited from the training program in areas of functional fitness. Unfortunately, there was no significant improvement with the Biodex balance system’s Fall Risk Test or Limits of Stability Test. Results may be due to the participants already having good balance as they were well below the normative data for risk of falling. It could also be because the training was not specific enough for improvements in the Fall Risk and Limits of Stability tests

Realistic Adversarial Data Augmentation for MR Image Segmentation

Neural network-based approaches can achieve high accuracy in various medical image segmentation tasks. However, they generally require large labelled datasets for supervised learning. Acquiring and manually labelling a large medical dataset is expensive and sometimes impractical due to data sharing and privacy issues. In this work, we propose an adversarial data augmentation method for training neural networks for medical image segmentation. Instead of generating pixel-wise adversarial attacks, our model generates plausible and realistic signal corruptions, which models the intensity inhomogeneities caused by a common type of artefacts in MR imaging: bias field. The proposed method does not rely on generative networks, and can be used as a plug-in module for general segmentation networks in both supervised and semi-supervised learning. Using cardiac MR imaging we show that such an approach can improve the generalization ability and robustness of models as well as provide significant improvements in low-data scenarios

Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model

Background: Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model. / Methods: C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5 mg/kg), or 5xDTG (12.5 mg/kg) both administered orally with 50 mg/kg tenofovir disoproxil fumarate 33.3 mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified. / Findings: 313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls. / Interpretation: Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs. / Funding: This project has been funded by Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 Canada Research Chair in Maternal-Child Health and HIV. HM is supported by a Junior Investigator award from the Ontario HIV Treatment Network

Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline

Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF), it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200 mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10 mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS). Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti

MSLED, Neutrino Oscillations and the Cosmological Constant

We explore the implications for neutrino masses and mixings within the minimal version of the supersymmetric large-extra-dimensions scenario (MSLED). This model was proposed in {\tt hep-ph/0404135} to extract the phenomenological implications of the promising recent attempt (in {\tt hep-th/0304256}) to address the cosmological constant problem. Remarkably, we find that the simplest couplings between brane and bulk fermions within this approach can lead to a phenomenologically-viable pattern of neutrino masses and mixings that is also consistent with the supernova bounds which are usually the bane of extra-dimensional neutrino models. Under certain circumstances the MSLED scenario can lead to a lepton mixing (PMNS) matrix close to the so-called bi-maximal or the tri-bimaximal forms (which are known to provide a good description of the neutrino oscillation data). We discuss the implications of MSLED models for neutrino phenomenology.Comment: 38 pages, 1 figure; Reposted with a few additional reference

Casimir Energies for 6D Supergravities Compactified on T_2/Z_N with Wilson Lines

We compute (as functions of the shape and Wilson-line moduli) the one-loop Casimir energy induced by higher-dimensional supergravities compactified from 6D to 4D on 2-tori, and on some of their Z_N orbifolds. Detailed calculations are given for a 6D scalar field having an arbitrary 6D mass m, and we show how to extend these results to higher-spin fields for supersymmetric 6D theories. Particular attention is paid to regularization issues and to the identification of the divergences of the potential, as well as the dependence of the result on m, including limits for which m^2 A> 1 where A is the volume of the internal 2 dimensions. Our calculation extends those in the literature to very general boundary conditions for fields about the various cycles of these geometries. The results have potential applications towards Supersymmetric Large Extra Dimensions (SLED) as a theory of the Dark Energy. First, they provide an explicit calculation within which to follow the dependence of the result on the mass of the bulk states which travel within the loop, and for heavy masses these results bear out the more general analysis of the UV-sensitivity obtained using heat-kernel methods. Second, because the potentials we find describe the dynamics of the classical flat directions of these compactifications, within SLED they would describe the present-day dynamics of the Dark Energy.Comment: 40 pages, 7 figure