Synthesis of Subject-Specific Human Balance Responses using a Task-Level Neuromuscular Control Platform

Many activities of daily living require a high level of neuromuscular coordination and balance control to avoid falls. Complex musculoskeletal models paired with detailed neuromuscular simulations complement experimental studies and uncover principles of coordinated and uncoordinated movements. Here, we created a closed-loop forward dynamic simulation framework that utilizes a detailed musculoskeletal model (19 degrees of freedom, and 92 Muscles) to synthesize human balance responses after support-surface perturbation. In addition, surrogate response models of task-level experimental kinematics from two healthy subjects were provided as inputs to our closedloop simulations to inform the design of the task-level controller. The predicted muscle EMGs and the resulting synthesized subject joint angles showed good conformity with the average of experimental trials. The simulated whole-body center of mass displacements, generated from a single kinematics trial per perturbation direction, were on average, within 7 mm (anterior perturbations) and 13 mm (posterior perturbations) of experimental displacements. Our results confirmed how a complex subject-specific movement can be reconstructed by sequencing and prioritizing multiple task-level commands to achieve desired movements. By combining the multidisciplinary approaches of robotics and biomechanics, the platform demonstrated here offers great potential for studying human movement control and subject-specific outcome prediction

Diet in Medieval Gaelic Ireland: A multiproxy study of the human remains from Ballyhanna, Co. Donegal

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThis study investigates the nature of diet in a predominantly Late Medieval Gaelic Irish skeletal population and explores whether any sex-based and/or age differences were evident in the population. A smaller sub-sample was also examined to determine whether there was any evidence for dietary change over time between the Early Medieval (c.700–c.1200) and Late Medieval periods (c.1200–c.1600). The dietary evidence was derived using a multiproxy approach that combined information from dental palaeopathology (n = 356 adults) and analysis of carbon (δ13C) and nitrogen (δ15N) stable isotope compositions (n = 72 individuals). A higher proportion of females were affected by carious lesions when compared to males. This is possibly suggestive of differing levels of carbohydrate consumption between the sexes, although other factors such as eating habits, and genetic and physiological differences may also have influenced the patterns in the data. The isotopic values indicated that both sexes were consuming similar amounts and types (marine vs. terrestrial) of dietary protein. Elevated δ15N indicated breastfeeding among the youngest in society but, once children had been weaned, the dietary protein was isotopically similar across the different age categories. Among a smaller radiocarbon-dated sub-sample (n = 37), there was an increase in both the percentage of individuals affected by dental caries and the percentage of teeth affected by dental caries between the Early Medieval and Late Medieval periods. This increase may indicate a greater inclusion of plant-based carbohydrates, such as cereals, in the diet over time, although it may also reflect the younger age distribution of the Early Medieval sample. Interpretations for each of these patterns are discussed with reference to the historical and archaeological evidence. Multiproxy palaeodietary studies for Medieval Ireland are limited and this is the first substantial study of evidence derived from both dental palaeopathology and stable isotope analysis.Transport Infrastructure Irelan

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

The inter-laboratory equivalence for lower limb kinematics and kinetics during unplanned sidestepping

Much inter-intra-tester kinematic and kinetic repeatability research exists, with a paucity investigating inter-laboratory equivalence. The objective of this research was to evaluate the inter-laboratory equivalence between time varying unplanned kinematics and moments of unplanned sidestepping (UnSS). Eight elite female athletes completed an established UnSS procedure motion capture laboratories in the UK and Australia. Three dimensional time varying unplanned sidestepping joint kinematics and moments were compared. Discrete variables were change of direction angles and velocity. Waveform data were compared using mean differences, 1D 95%CI and RMSE. Discrete variables were compared using 0D 95% CI. The mean differences and 95%CI for UnSS kinematics broadly supported equivalence between laboratories (RMSE≤5.1°). Excluding hip flexion/extension moments (RMSE = 1.04 Nm/kg), equivalence was also supported for time varying joint moments between laboratories (RMSE≤0.40 Nm/kg). Dependent variables typically used to characterise UnSS were also equivalent. When consistent experimental and modelling procedures are employed, consistent time varying UnSS lower limb joint kinematic and moment estimates between laboratories can be obtained. We therefore interpret these results as a support of equivalence, yet highlight the challenges of establishing between-laboratory experiments or data sharing, as well as establishing appropriate ranges of acceptable uncertainty. These findings are important for data sharing and multi-centre trials

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

Current diagnosis and treatment algorithms for anal incontinence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75666/1/j.1464-410X.2006.06307.x.pd

Selective P2X7 receptor antagonists for chronic inflammation and pain

ATP, acting on P2X7 receptors, stimulates changes in intracellular calcium concentrations, maturation, and release of interleukin-1β (IL-1β), and following prolonged agonist exposure, cell death. The functional effects of P2X7 receptor activation facilitate several proinflammatory processes associated with arthritis. Within the nervous system, these proinflammatory processes may also contribute to the development and maintenance of chronic pain. Emerging data from genetic knockout studies have indicated specific roles for P2X7 receptors in inflammatory and neuropathic pain states. The discovery of multiple distinct chemical series of potent and highly selective P2X7 receptor antagonists have enhanced our understanding of P2X7 receptor pharmacology and the diverse array of P2X7 receptor signaling mechanisms. These antagonists have provided mechanistic insight into the role(s) P2X7 receptors play under pathophysiological conditions. In this review, we integrate the recent discoveries of novel P2X7 receptor-selective antagonists with a brief update on P2X7 receptor pharmacology and its therapeutic potential