Mindfulness-based interventions in multiple sclerosis : beneficial effects of Tai Chi on balance, coordination, fatigue and depression

BACKGROUND: Patients suffering from Multiple Sclerosis (MS) experience a wide array of symptoms, including balance problems, mobility impairment, fatigue and depression. Physical exercise has recently been acknowledged as a treatment option complementary to medication. However, information regarding putative effects of structured exercise programs on neurological symptoms is sparse. Tai Chi, a Chinese martial art incorporating physical exercise and mindfulness training, has been shown to yield health benefits in various neurological groups. It seems particularly suitable for patients with motoric deficits as it challenges coordination and balance. The purpose of the current study was to explore the therapeutic value of structured Tai Chi training for coordination, balance, fatigue and depression in mildly disabled MS patients. METHODS: A sample of 32 MS patients (Expanded Disability Status Scale, EDSS < 5) was examined. A structured Tai Chi course was devised and a Tai Chi group participated in two weekly sessions of 90 minutes duration for six months, while a comparison group received treatment as usual (TAU). Both groups were examined prior to and following the six-months interval with regards to balance and coordination performance as well as measures of fatigue, depression and life satisfaction. RESULTS: Following the intervention, the Tai Chi group showed significant, consistent improvements in balance, coordination, and depression, relative to the TAU group (range of effect-sizes: partial η(2) = 0.16 – 0.20). Additionally, life satisfaction improved (partial η(2) = 0.31). Fatigue deteriorated in the comparison group, whereas it remained relatively stable in the Tai Chi group (partial η(2) = 0.24). CONCLUSIONS: The consistent pattern of results confirms that Tai Chi holds therapeutic potential for MS patients. Further research is needed to determine underlying working mechanisms, and to verify the results in a larger sample and different MS subgroups

An exploration of impaired walking dynamics and fatigue in Multiple Sclerosis

BACKGROUND: Physical disability in multiple sclerosis (MS) is frequently characterized by impaired ambulation. Although walking tests have been successfully employed to assess walking ability in MS patients, data analytic procedures have predominantly relied on result-oriented parameters (e.g. total distance covered during a given amount of time), whereas process-oriented, dynamic walking patterns have mostly been ignored. This is striking, since healthy individuals have been observed to display a stereotypical U-shaped pattern of walking speed during timed walking, characterized by relatively high speed during the initial phase, subsequent slowing and final acceleration. Objective of the current study was to test the utility of the 6 min Walk (6MW) and the 12 min Walk (12MW) for revealing putatively abnormal temporal dynamic features of walking in MS. METHODS: A group of 37 MS patients was divided into subgroups with regard to their level of disability analyzed with the Expanded Disability Status Scale (EDSS; Mild MS Group, n = 20, EDSS 0 – 3.5; Moderate MS Group, n = 17, EDSS 4 – 5). Subsequently, both groups were compared to age-matched healthy controls (n = 25) on both tests with regard to result-oriented characteristics (mean walking speed), as well as dynamic features (mean decline in walking speed, degree of observed U-shape). RESULTS: Both MS groups showed a significantly lower mean walking speed than healthy controls, independent of test duration. Compared to controls, the Moderate MS Group also slowed down more rapidly throughout both tests. The same pronounced decline in walking speed was observed for the Mild MS Group in case of the 12MW. Additionally, for both MS groups an attenuated U-shaped velocity pattern was observed relative to controls in the 6MW. Patients' subjective fatigue scores were more strongly correlated with the decline in walking speed than with the common parameter of mean walking speed in the 6MW. CONCLUSIONS: MS patients display abnormal dynamics in their walking patterns. A pronounced linear decline in walking speed can be identified with the 12MW even in MS patients with seemingly mild disability. Similarly, the 6MW can be used to assess an abnormal walking profile. Particularly the linear decline in walking speed on this test shows a more robust association with subjective fatigue than mean walking speed. Dynamic walking parameters may hence represent valuable clinical features, serving as surrogate measures of motor fatigue. Future studies are needed to verify their prognostic value

Probing potential priming: Defining, quantifying, and testing the causal priming effect using the potential outcomes framework

Having previously seen an item helps uncover the item another time, given a perceptual or cognitive cue. Oftentimes, however, it may be difficult to quantify or test the existence and size of a perceptual or cognitive effect, in general, and a priming effect, in particular. This is because to examine the existence of and quantify the effect, one needs to compare two outcomes: the outcome had one previously seen the item vs. the outcome had one not seen the item. But only one of the two outcomes is observable. Here, we argue that the potential outcomes framework is useful to define, quantify, and test the causal priming effect. To demonstrate its efficacy, we apply the framework to study the priming effect using data from a between-subjects study involving English word identification. In addition, we show that what has been used intuitively by experimentalists to assess the priming effect in the past has a sound mathematical foundation. Finally, we examine the links between the proposed method in studying priming and the multinomial processing tree (MPT) model, and how to extend the method to study experimental paradigms involving exclusion and inclusion instructional conditions

Differential angiogenic roles of serum amyloid A 1 (SAA1) isoforms in esophageal squamous cell carcinoma (ESCC)

Molecular and Cellular Biology - Poster Presentations - Proffered Abstracts - Poster Presentations - Tumor Suppressors 2: abstract no. 1550This journal suppl. entitled: Proceedings: AACR Annual Meeting 2014; April 5-9, 2014 ...Esophageal Caner (EC), a highly metastatic and fatal cancer, is ranked the eighth in mortality rate in Hong Kong cancer patients (Hong Kong Cancer Registry, Hospital Authority, 2010). Esophageal Squamous Cell Carcinoma (ESCC) is the predominant type comprising more than 90% of EC. Using a functional complementation approach, SAA1 was identified as one of the tumor suppressor gene candidates. SAA1 is located at chromosome 11p15.1 and is expressed as a secretary protein in liver, human cultured smooth muscle cells, monocyte-macrophage cell lines, and in histologically-normal human epithelial tissues. Genetic polymorphisms of SAA1 have been identified as a risk factor of diseases such as amyloidosis. Three SAA1 isoforms with two ...postprin

Towards More Accurate Automatic Sleep Staging via Deep Transfer Learning.

BACKGROUND: Despite recent significant progress in the development of automatic sleep staging methods, building a good model still remains a big challenge for sleep studies with a small cohort due to the data-variability and data-inefficiency issues. This work presents a deep transfer learning approach to overcome these issues and enable transferring knowledge from a large dataset to a small cohort for automatic sleep staging. METHODS: We start from a generic end-to-end deep learning framework for sequence-to-sequence sleep staging and derive two networks as the means for transfer learning. The networks are first trained in the source domain (i.e. the large database). The pretrained networks are then finetuned in the target domain (i.e. the small cohort) to complete knowledge transfer. We employ the Montreal Archive of Sleep Studies (MASS) database consisting of 200 subjects as the source domain and study deep transfer learning on three different target domains: the Sleep Cassette subset and the Sleep Telemetry subset of the Sleep-EDF Expanded database, and the Surrey-cEEGrid database. The target domains are purposely adopted to cover different degrees of data mismatch to the source domains. RESULTS: Our experimental results show significant performance improvement on automatic sleep staging on the target domains achieved with the proposed deep transfer learning approach. CONCLUSIONS: These results suggest the efficacy of the proposed approach in addressing the above-mentioned data-variability and data-inefficiency issues. SIGNIFICANCE: As a consequence, it would enable one to improve the quality of automatic sleep staging models when the amount of data is relatively small

Personalized automatic sleep staging with single-night data: a pilot study with Kullback-Leibler divergence regularization.

OBJECTIVE: Brain waves vary between people. This work aims to improve automatic sleep staging for longitudinal sleep monitoring via personalization of algorithms based on individual characteristics extracted from sleep data recorded during the first night. APPROACH: As data from a single night are very small, thereby making model training difficult, we propose a Kullback-Leibler (KL) divergence regularized transfer learning approach to address this problem. We employ the pretrained SeqSleepNet (i.e. the subject independent model) as a starting point and finetune it with the single-night personalization data to derive the personalized model. This is done by adding the KL divergence between the output of the subject independent model and it of the personalized model to the loss function during finetuning. In effect, KL-divergence regularization prevents the personalized model from overfitting to the single-night data and straying too far away from the subject independent model. MAIN RESULTS: Experimental results on the Sleep-EDF Expanded database consisting of 75 subjects show that sleep staging personalization with single-night data is possible with help of the proposed KL-divergence regularization. On average, we achieve a personalized sleep staging accuracy of 79.6%, a Cohen's kappa of 0.706, a macro F1-score of 73.0%, a sensitivity of 71.8%, and a specificity of 94.2%. SIGNIFICANCE: We find both that the approach is robust against overfitting and that it improves the accuracy by 4.5 percentage points compared to the baseline method without personalization and 2.2 percentage points compared to it with personalization but without regularization

Rituximab versus cyclophosphamide as first steroid sparing agent in childhood frequently relapsing and steroid dependent nephrotic syndrome

Background: Approximately 50% of children with steroid-sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications. Methods: A prospective open-label non-randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia, or active infection. The recruited children were allocated either to the oral cyclophosphamide (3 mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months. Results: Forty-six subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR 0.36; 95% CI 0.09–1.45; p = 0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N = 10) and 6.3 months in the rituximab group (N = 3). Both treatments were associated with a significant (p < 0.001) reduction in prescribed dose of oral alternate-day steroid from 1.02 to 0.36 mg/kg (cyclophosphamide) and 0.86 to 0.08 mg/kg (rituximab). Importantly, a significantly (p = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity besides severe leucopenia and neutropenia in the 7th week of treatment with complete recovery with the withdrawal of cyclophosphamide and maintenance of remission. A minor infusion-related reaction in the form of a generalized macular skin rash was observed in one patient (5%) in the rituximab group. Conclusions: Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide

On the Globular Cluster IMF below 1 Solar Mass

(Abridged) Accurate luminosity functions (LF) for a dozen globular clusters have now been measured at or just beyond their half-light radius using HST. They span almost the entire cluster main sequence below ~ 0.75 Msolar. All these clusters exhibit LF that rise continuously from an absolute I magnitude M_I ~ 6 to a peak at M_I ~ 8.5-9 and then drop with increasing M_I. Transformation of the LF into mass functions (MF) by means of the most recent mass luminosity relations that are consistent with all presently available data on the physical properties of low mass, low metallicity stars shows that all the LF observed so far can be obtained from MF having the shape of a log-normal distribution with characteristic mass m_c=0.33 +/- 0.03 Msolar and standard deviation sigma = 1.81 +/- 0.19. After correction for the effects of mass segregation, the variation of the ratio of the number of higher to lower mass stars with cluster mass or any simple orbital parameter or the expected time to disruption recently computed for these clusters shows no statistically significant trend over a range of this last parameter of more than a factor of 100. We conclude that the global MF of these clusters have not been measurably modified by evaporation and tidal interactions with the Galaxy and, thus, should reflect the initial distribution of stellar masses. Since the log-normal function that we find is also very similar to the one obtained independently for much younger clusters and to the form expected theoretically, the implication seems to be unavoidable that it represents the true stellar IMF for this type of stars in this mass range.Comment: Accepted for publication in The Astrophysical Journal. Contains 28 pages with 6 figure

Mycobacterium tuberculosis Complex Lipid Virulence Factors Preserved in the 17,000 Year Old Skeleton of an Extinct Bison, Bison antiquus

Tracing the evolution of ancient diseases depends on the availability and accessibility of suitable biomarkers in archaeological specimens. DNA is potentially information-rich but it depends on a favourable environment for preservation. In the case of the major mycobacterial pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, robust lipid biomarkers are established as alternatives or complements to DNA analyses. A DNA report, a decade ago, suggested that a 17,000 year old skeleton of extinct Bison antiquus, from Natural Trap Cave, Wyoming, was the oldest known case of tuberculosis. In the current study, key mycobacterial lipid virulence factor biomarkers were detected in the same two samples from this bison. Fluorescence high-performance liquid chromatography (HPLC) indicated the presence of mycolic acids of the mycobacterial type, but they were degraded and could not be precisely correlated with tuberculosis. However, pristine profiles of C29, C30 and C32 mycocerosates and C27 mycolipenates, typical of the Mycobacterium tuberculosis complex, were recorded by negative ion chemical ionization gas chromatography mass spectrometry of pentafluorobenzyl ester derivatives. These findings were supported by the detection of C34 and C36 phthiocerols, which are usually esterified to the mycocerosates. The existence of Pleistocene tuberculosis in the Americas is confirmed and there are many even older animal bones with well-characterised tuberculous lesions similar to those on the analysed sample. In the absence of any evidence of tuberculosis in human skeletons older than 9,000 years BP, the hypothesis that this disease evolved as a zoonosis, before transfer to humans, is given detailed consideration and discussion