666 research outputs found

    Insights and improvements in correspondence between axonal volume fraction measured with diffusion-weighted MRI and electron microscopy

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    Biophysical diffusion-weighted imaging (DWI) models are increasingly used in neuroscience to estimate the axonal water fraction ((Formula presented.)), which in turn is key for noninvasive estimation of the axonal volume fraction ((Formula presented.)). These models require thorough validation by comparison with a reference method, for example, electron microscopy (EM). While EM studies often neglect the unmyelinated axons and solely report the fraction of myelinated axons, in DWI both myelinated and unmyelinated axons contribute to the DWI signal. However, DWI models often include simplifications, for example, the neglect of differences in the compartmental relaxation times or fixed diffusivities, which in turn might affect the estimation of (Formula presented.). We investigate whether linear calibration parameters (scaling and offset) can improve the comparability between EM- and DWI-based metrics of (Formula presented.). To this end, we (a) used six DWI models based on the so-called standard model of white matter (WM), including two models with fixed compartmental diffusivities (e.g., neurite orientation dispersion and density imaging, NODDI) and four models that fitted the compartmental diffusivities (e.g., white matter tract integrity, WMTI), and (b) used a multimodal data set including ex vivo diffusion DWI and EM data in mice with a broad dynamic range of fibre volume metrics. We demonstrated that the offset is associated with the volume fraction of unmyelinated axons and the scaling factor is associated with different compartmental (Formula presented.) and can substantially enhance the comparability between EM- and DWI-based metrics of (Formula presented.). We found that DWI models that fitted compartmental diffusivities provided the most accurate estimates of the EM-based (Formula presented.). Finally, we introduced a more efficient hybrid calibration approach, where only the offset is estimated but the scaling is fixed to a theoretically predicted value. Using this approach, a similar one-to-one correspondence to EM was achieved for WMTI. The method presented can pave the way for use of validated DWI-based models in clinical research and neuroscience

    Pulsed electromagnetic energy treatment offers no clinical benefit in reducing the pain of knee osteoarthritis: a systematic review

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    Background The rehabilitation of knee osteoarthritis often includes electrotherapeutic modalities as well as advice and exercise. One commonly used modality is pulsed electromagnetic field therapy (PEMF). PEMF uses electro magnetically generated fields to promote tissue repair and healing rates. Its equivocal benefit over placebo treatment has been previously suggested however recently a number of randomised controlled trials have been published that have allowed a systematic review to be conducted. Methods A systematic review of the literature from 1966 to 2005 was undertaken. Relevant computerised bibliographic databases were searched and papers reviewed independently by two reviewers for quality using validated criteria for assessment. The key outcomes of pain and functional disability were analysed with weighted and standardised mean differences being calculated. Results Five randomised controlled trials comparing PEMF with placebo were identified. The weighted mean differences of the five papers for improvement in pain and function, were small and their 95% confidence intervals included the null. Conclusion This systematic review provides further evidence that PEMF has little value in the management of knee osteoarthritis. There appears to be clear evidence for the recommendation that PEMF does not significantly reduce the pain of knee osteoarthritis

    Effects of increase in temperature and open water on transmigration and access to health care by the Nenets reindeer herders in northern Russia

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    Background . The indigenous Nenets reindeer herders in northern Russia annually migrate several hundred kilometers between summer and winter pastures. In the warming climate, ice-rich permafrost and glaciers are being significantly reduced and will eventually disappear from parts of the Arctic. The emergent changes in hydrological cycles have already led to substantial increases in open water that stays unfrozen for longer periods of time. This environmental change has been reported to compromise the nomadic Nenets’ traditional way of life because the presence of new water in the tundra reduces the Nenets’ ability to travel by foot, sled, or motor vehicle from the summer transitory tundra campsites in order to access healthcare centers in villages. New water can also impede their access to family and community at other herder camps and in the villages. Although regional and global models predicting hydrologic changes due to climate changes exist, the spatial resolution of these models is too coarse for studying how increases in open water affect health and livelihoods. To anticipate the full health impact of hydrologic changes, the current gap between globally forecasted scenarios and locally forecasted hydrologic scenarios needs to be bridged. Objectives . We studied the effects of the autumn temperature anomalies and increases in open water on health care access and transmigration of reindeer herders on the Kanin Peninsula. Design . Correlational and time series analyses were completed. Methods . The study population consisted of 370 full-time, nomadic reindeer herders. We utilized clinical visit records, studied surface temperature anomalies during autumn migrations, and used remotely sensed imagery to detect water bodies. Spearman correlation was used to measure the relationship between temperature anomalies and the annual arrival of the herders at the Nes clinic for preventive and primary care. Piecewise regression was used to model change in mean autumnal temperature anomalies over time. We also created a water body product to detect inter-annual changes in water area. Results . Correlation between arrivals to the Nes clinic and temperature anomalies during the fall transmigration (1979–2011) was r = 0.64, p = 0.0004; 95% CI (0.31; 0.82). Regression analysis estimated that mean temperature anomalies during the fall migration in September–December were stochastically stationary pre-1991 and have been rising significantly (p < 0.001) since then. The rate of change was estimated at +0.1351°C/year, SE = 0.0328, 95% CI (+0.0694, +0.2007). The amount of detected water fluctuated significantly interannually (620–800 km2). Conclusions . Later arrival of freezing temperatures in the autumn followed by the earlier spring thaws and more open water delay transmigration and reduce herders’ access to health care. The recently observed delays in arrival to the clinic are likely related to the warming trend and to concomitant hydrologic changes

    Random walk with barriers: Diffusion restricted by permeable membranes

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    Restrictions to molecular motion by barriers (membranes) are ubiquitous in biological tissues, porous media and composite materials. A major challenge is to characterize the microstructure of a material or an organism nondestructively using a bulk transport measurement. Here we demonstrate how the long-range structural correlations introduced by permeable membranes give rise to distinct features of transport. We consider Brownian motion restricted by randomly placed and oriented permeable membranes and focus on the disorder-averaged diffusion propagator using a scattering approach. The renormalization group solution reveals a scaling behavior of the diffusion coefficient for large times, with a characteristically slow inverse square root time dependence. The predicted time dependence of the diffusion coefficient agrees well with Monte Carlo simulations in two dimensions. Our results can be used to identify permeable membranes as restrictions to transport in disordered materials and in biological tissues, and to quantify their permeability and surface area.Comment: 8 pages, 3 figures; origin of dispersion clarified, refs adde

    Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

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    The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

    The frequency of osteogenic activities and the pattern of intermittence between periods of physical activity and sedentary behaviour affects bone mineral content: the cross-sectional NHANES study

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    BACKGROUND: Sedentary behaviours, defined as non exercising seated activities, have been shown to have deleterious effects on health. It has been hypothesised that too much sitting time can have a detrimental effect on bone health in youth. The aim of this study is to test this hypothesis by exploring the association between objectively measured volume and patterns of time spent in sedentary behaviours, time spent in specific screen-based sedentary pursuits and bone mineral content (BMC) accrual in youth. METHODS: NHANES 2005–2006 cycle data includes BMC of the femoral and spinal region via dual-energy X-ray absorptiometry (DEXA), assessment of physical activity and sedentary behaviour patterns through accelerometry, self reported time spent in screen based pursuits (watching TV and using a computer), and frequency of vigorous playtime and strengthening activities. Multiple regression analysis, stratified by gender was performed on N = 671 males and N = 677 females aged from 8 to 22 years. RESULTS: Time spent in screen-based sedentary behaviours is negatively associated with femoral BMC (males and females) and spinal BMC (females only) after correction for time spent in moderate and vigorous activity. Regression coefficients indicate that an additional hour per day of screen-based sitting corresponds to a difference of −0.77 g femoral BMC in females [95% CI: -1.31 to −0.22] and of −0.45 g femoral BMC in males [95% CI: -0.83 to −0.06]. This association is attenuated when self-reported engagement in regular (average 5 times per week) strengthening exercise (for males) and vigorous playing (for both males and females) is taken into account. Total sitting time and non screen-based sitting do not appear to have a negative association with BMC, whereas screen based sedentary time does. Patterns of intermittence between periods of sitting and moderate to vigorous activity appears to be positively associated with bone health when activity is clustered in time and inter-spaced with long continuous bouts of sitting. CONCLUSIONS: Some specific sedentary pursuits (screen-based) are negatively associated with bone health in youth. This association is specific to gender and anatomical area. This relationship between screen-based time and bone health is independent of the total amount of physical activity measured objectively, but not independent of self-reported frequency of strengthening and vigorous play activities. The data clearly suggests that the frequency, rather than the volume, of osteogenic activities is important in counteracting the effect of sedentary behaviour on bone health. The pattern of intermittence between sedentary periods and activity also plays a role in bone accrual, with clustered short bouts of activity interspaced with long periods of sedentary behaviours appearing to be more beneficial than activities more evenly spread in time
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