Muscle Fatigue Analysis Using OpenSim

In this research, attempts are made to conduct concrete muscle fatigue analysis of arbitrary motions on OpenSim, a digital human modeling platform. A plug-in is written on the base of a muscle fatigue model, which makes it possible to calculate the decline of force-output capability of each muscle along time. The plug-in is tested on a three-dimensional, 29 degree-of-freedom human model. Motion data is obtained by motion capturing during an arbitrary running at a speed of 3.96 m/s. Ten muscles are selected for concrete analysis. As a result, the force-output capability of these muscles reduced to 60%-70% after 10 minutes' running, on a general basis. Erector spinae, which loses 39.2% of its maximal capability, is found to be more fatigue-exposed than the others. The influence of subject attributes (fatigability) is evaluated and discussed

Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis

Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users

Last Encounter Routing under Random Waypoint Mobility

Last Encounter Routing (LER) algorithms for mobile ad hoc networks rely only on encounter histories at every node to route packets, and therefore do not need control traffic to track topology changes due to node mobility. LER exploits the fact that past information about a node`s mobility helps to locate that node in the future. As we have pointed out in earlier work \cite{mg}, the performance of LER algorithms depends on the mobility processes of nodes. In this paper, we ask whether LER can work under the random waypoint (RWP) mobility model. This question is important for several reasons. First, as shown in \cite{mg}, a good performance for the RWP model is harder to achieve than for another prominent mobility model, the random walk. This is because the RWP model has a much shorter relaxation time, i.e., a time-horizon over which past information is still useful. Also, the RWP model has a much less favorable ratio of number of encounters between nodes and the traveled distance. Second, in contrast to the random walk, the RWP model is predictable. This provides us with an opportunity to exploit additional information collected in an encounter (such as speed, direction, etc.) to improve routing. We formally define the RWP model, and compute the optimal predictors for several observation sets, i.e., observed parameters of node mobility. We develop a new LER algorithm tuned to the RWP model called GREASE-RWP, and present simulation results that demonstrate that an efficient and scalable LER for the RWP model is possible

Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Climate model response from the Geoengineering Model Intercomparison Project (GeoMIP)

Solar geoengineering - deliberate reduction in the amount of solar radiation retained by the Earth - has been proposed as a means of counteracting some of the climatic effects of anthropogenic greenhouse gas emissions. We present results from Experiment G1 of the Geoengineering Model Intercomparison Project, in which 12 climate models have simulated the climate response to an abrupt quadrupling of CO2 from preindustrial concentrations brought into radiative balance via a globally uniform reduction in insolation. Models show this reduction largely offsets global mean surface temperature increases due to quadrupled CO2 concentrations and prevents 97% of the Arctic sea ice loss that would otherwise occur under high CO2 levels but, compared to the preindustrial climate, leaves the tropics cooler (-0.3 K) and the poles warmer (+0.8 K). Annual mean precipitation minus evaporation anomalies for G1 are less than 0.2 mm day-1 in magnitude over 92% of the globe, but some tropical regions receive less precipitation, in part due to increased moist static stability and suppression of convection. Global average net primary productivity increases by 120% in G1 over simulated preindustrial levels, primarily from CO2 fertilization, but also in part due to reduced plant heat stress compared to a high CO2 world with no geoengineering. All models show that uniform solar geoengineering in G1 cannot simultaneously return regional and global temperature and hydrologic cycle intensity to preindustrial levels. Key Points Temperature reduction from uniform geoengineering is not uniform Geoengineering cannot offset both temperature and hydrology changes NPP increases mostly due to CO2 fertilization ©2013. American Geophysical Union. All Rights Reserved.BK is supported by the Fund for Innovative Climate and Energy Research. Simulations performed by BK were supported by the NASA High-End Computing (HEC) Program through the NASA Center for Climate Simulation (NCCS) at Goddard Space Flight Center. The Pacific Northwest National Laboratory is operated for the U.S. Department of Energy by Battelle Memorial Institute under contract DE-AC05-76RL01830. AR is supported by US National Science Foundation grant AGS-1157525. JMH and AJ were supported by the joint DECC/Defra Met Office Hadley Centre Climate Programme (GA01101). KA, DBK, JEK, UN, HS, and MS received funding from the European Union’s Seventh Framework Programme (FP7/ 2007–2013) under grant agreement 226567-IMPLICC. KA and JEK received support from the Norwegian Research Council’s Programme for Supercomputing (NOTUR) through a grant of computing time. Simulations with the IPSL-CM5 model were supported through HPC resources of [CCT/ TGCC/CINES/IDRIS] under the allocation 2012-t2012012201 made by GENCI (Grand Equipement National de Calcul Intensif). DJ and JCM thank all members of the BNU-ESM model group, as well as the Center of Information and Network Technology at Beijing Normal University for assistance in publishing the GeoMIP data set. The National Center for Atmospheric Research is funded by the National Science Foundation. SW was supported by the Innovative Program of Climate Change Projection for the 21st century, MEXT, Japan. Computer resources for PJR, BS, and JHY were provided by the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under contract DE-AC02-05CH11231

Childbearing intentions in a low fertility context: the case of Romania

This paper applies the Theory of Planned Behaviour (TPB) to find out the predictors of fertility intentions in Romania, a low-fertility country. We analyse how attitudes, subjective norms and perceived behavioural control relate to the intention to have a child among childless individuals and one-child parents. Principal axis factor analysis confirms which items proposed by the Generation and Gender Survey (GGS 2005) act as valid and reliable measures of the suggested theoretical socio-psychological factors. Four parity-specific logistic regression models are applied to evaluate the relationship between the socio-psychological factors and childbearing intentions. Social pressure emerges as the most important aspect in fertility decision-making among childless individuals and one-child parents, and positive attitudes towards childbearing are a strong component in planning for a child. This paper also underlines the importance of the region-specific factors when studying childbearing intentions: planning for the second child significantly differs among the development regions, representing the cultural and socio-economic divisions of the Romanian territory

Liposarcoma: exploration of clinical prognostic factors for risk based stratification of therapy

<p>Abstract</p> <p>Background</p> <p>Prognosis and optimal treatment strategies of liposarcoma have not been fully defined. The purpose of this study is to define the distinctive clinical features of liposarcomas by assessing prognostic factors.</p> <p>Methods</p> <p>Between January 1995 and May 2008, 94 liposarcoma patients who underwent surgical resection with curative intent were reviewed.</p> <p>Results</p> <p>Fifty patients (53.2%) presented with well differentiated, 22 (23.4%) myxoid, 15 (16.0%) dedifferentiated, 5 (5.3%) round cell, and 2 (2.1%) pleomorphic histology. With the median 14 cm sized of tumor burden, about half of the cases were located in the retroperitoneum (46.8%). Seventy two (76.6%) patients remained alive with 78.1%, and 67.5% of the 5- and 10-year overall survival (OS) rates, respectively. Low grade liposarcoma (well differentiated and myxoid) had a significantly prolonged OS and disease free survival (DFS) with adjuvant radiotherapy when compared with those without adjuvant radiotherapy (5-year OS, 100% vs 66.3%, P = 0.03; 1-year DFS, 92.9% <it>vs </it>50.0%, respectively, P = 0.04). Independent prognostic factors for OS were histologic variant (P = 0.001; HR, 5.1; 95% CI, 2.0 – 12.9), and margin status (P = 0.005; HR, 4.1; 95% CI, 1.6–10.5). We identified three different risk groups: group 1 (n = 66), no adverse factors; group 2, one or two adverse factors (n = 28). The 5-year OS rate for group 1, and 2 were 91.9%, 45.5%, respectively.</p> <p>Conclusion</p> <p>The histologic subtype, and margin status were independently associated with OS, and adjuvant radiotherapy seems to confer survival benefit in low grade tumors. Our prognostic model for primary liposarcoma demonstrated distinct three groups of patients with good prognostic discrimination.</p

Elevated MED28 expression predicts poor outcome in women with breast cancer

Abstract Background MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression. Methods Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed. Results MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death. Conclusions We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer

A self-rectifying TaOy/nanoporous TaOx memristor synaptic array for learning and energy-efficient neuromorphic systems

The human brain intrinsically operates with a large number of synapses, more than 10(15). Therefore, one of the most critical requirements for constructing artificial neural networks (ANNs) is to achieve extremely dense synaptic array devices, for which the crossbar architecture containing an artificial synaptic node at each cross is indispensable. However, crossbar arrays suffer from the undesired leakage of signals through neighboring cells, which is a major challenge for implementing ANNs. In this work, we show that this challenge can be overcome by using Pt/TaOy/nanoporous (NP) TaOx/Ta memristor synapses because of their self-rectifying behavior, which is capable of suppressing unwanted leakage pathways. Moreover, our synaptic device exhibits high non-linearity (up to 10(4)), low synapse coupling (S.C, up to 4.00 x 10(-5)), acceptable endurance (5000 cycles at 85 degrees C), sweeping (1000 sweeps), retention stability and acceptable cell uniformity. We also demonstrated essential synaptic functions, such as long-term potentiation (LTP), long-term depression (LTD), and spiking-timing-dependent plasticity (STDP), and simulated the recognition accuracy depending on the S.C for MNIST handwritten digit images. Based on the average S.C (1.60 x 10(-4)) in the fabricated crossbar array, we confirmed that our memristive synapse was able to achieve an 89.08% recognition accuracy after only 15 training epochs