Feasibility and safety of combining repetitive transcranial magnetic stimulation and quadriceps strengthening exercise for chronic pain in knee osteoarthritis: A study protocol for a pilot randomised controlled trial

Introduction Knee osteoarthritis is a leading cause of disability, resulting in pain and reduced quality of life. Exercise is the cornerstone of conservative management but effects are, at best, moderate. Early evidence suggests that repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor cortex (M1) may improve the effect of exercise in knee osteoarthritis. This pilot study aims to (1) determine the feasibility, safety and participant-rated response to an intervention adding M1 rTMS to exercise in knee osteoarthritis; (2) elucidate physiological mechanisms in response to the intervention; (3) provide data to conduct a sample size calculation for a fully powered trial. Methods and analysis This is a pilot randomised, assessor-blind, therapist-blind and participant-blind, sham-controlled trial. Thirty individuals with painful knee osteoarthritis will be recruited and randomly allocated to receive either: (1) active rTMS+exercise or (2) sham rTMS+exercise intervention. Participants will receive 15 min of either active or sham rTMS immediately prior to 30 min of supervised muscle strengthening exercise (2×/week, 6 weeks) and complete unsupervised home exercises. Outcome measures of feasibility, safety, pain, function and physiological mechanisms will be assessed before and/or after the intervention. Feasibility and safety will be analysed using descriptive analysis. Within-group and between-group comparisons of pain and function will be conducted to examine trends of efficacy. Ethics and dissemination This study has been approved by the University of New South Wales Human Research Ethics Committee (HC210954). All participants will provide written informed consent. The study results will be submitted for peer-reviewed publication. Trial registration number ACTRN12621001712897p

Post-transcriptional Regulation of NK Cell Activation

Natural killer (NK) cells play key roles in innate and adaptive immune defenses. NK cell responses are mediated by two major mechanisms: the direct cytolysis of target cells, and immune regulation by production of various cytokines. Many previous reports show that the complex NK cell activation process requires de novo gene expression regulated at both transcriptional and post-transcriptional levels. Specialized un-translated regions (UTR) of mRNAs are the main mechanisms of post-transcriptional regulation. Analysis of post-transcriptional regulation is needed to clearly understand NK cell biology and, furthermore, harness the power of NK cells for therapeutic aims. This review summarizes the current understanding of mRNA metabolism during NK cell activation, focusing primarily on post-transcriptional regulation

Optically tuned terahertz modulator based on annealed multilayer MoS2

Controlling the propagation properties of terahertz waves is very important in terahertz technologies applied in high-speed communication. Therefore a new-type optically tuned terahertz modulator based on multilayer-MoS 2 and silicon is experimentally demonstrated. The terahertz transmission could be significantly modulated by changing the power of the pumping laser. With an annealing treatment as a p-doping method, MoS 2 on silicon demonstrates a triple enhancement of terahertz modulation depth compared with the bare silicon. This MoS 2 -based device even exhibited much higher modulation efficiency than the graphene-based device. We also analyzed the mechanism of the modulation enhancement originated from annealed MoS 2, and found that it is different from that of graphene-based device. The unique optical modulating properties of the device exhibit tremendous promise for applications in terahertz switch

Assessment of NER solutions against the first and second CALBC Silver Standard Corpus

Background Competitions in text mining have been used to measure the performance of automatic text processing solutions against a manually annotated gold standard corpus (GSC). The preparation of the GSC is time-consuming and costly and the final corpus consists at the most of a few thousand documents annotated with a limited set of semantic groups. To overcome these shortcomings, the CALBC project partners (PPs) have produced a large-scale annotated biomedical corpus with four different semantic groups through the harmonisation of annotations from automatic text mining solutions, the first version of the Silver Standard Corpus (SSC-I). The four semantic groups are chemical entities and drugs (CHED), genes and proteins (PRGE), diseases and disorders (DISO) and species (SPE). This corpus has been used for the First CALBC Challenge asking the participants to annotate the corpus with their text processing solutions. Results All four PPs from the CALBC project and in addition, 12 challenge participants (CPs) contributed annotated data sets for an evaluation against the SSC-I. CPs could ignore the training data and deliver the annotations from their genuine annotation system, or could train a machine-learning approach on the provided pre-annotated data. In general, the performances of the annotation solutions were lower for entities from the categories CHED and PRGE in comparison to the identification of entities categorized as DISO and SPE. The best performance over all semantic groups were achieved from two annotation solutions that have been trained on the SSC-I. The data sets from participants were used to generate the harmonised Silver Standard Corpus II (SSC-II), if the participant did not make use of the annotated data set from the SSC-I for training purposes. The performances of the participants’ solutions were again measured against the SSC-II. The performances of the annotation solutions showed again better results for DISO and SPE in comparison to CHED and PRGE. Conclusions The SSC-I delivers a large set of annotations (1,121,705) for a large number of documents (100,000 Medline abstracts). The annotations cover four different semantic groups and are sufficiently homogeneous to be reproduced with a trained classifier leading to an average F-measure of 85%. Benchmarking the annotation solutions against the SSC-II leads to better performance for the CPs’ annotation solutions in comparison to the SSC-I

Scaling factors for channel width variations in treelike flow field patterns for polymer electrolyte membrane fuel cells - An experimental study

To have a uniform distribution of reactants is an advantage to a fuel cell. We report results for such a distributor with tree-like flow field plates (FFP). Numerical simulations have shown that the width scaling parameters of tree-like patterns in FFPs used in polymer electrolyte membrane fuel cells (PEMFC) reduces the viscous dissipation in the channels. In this study, experimental investigations were conducted on a 2-layer FF plate possessing a tree-like FF pattern which was CNC milled on high-quality graphite. Three FF designs of different width scaling parameters were employed. IeV curves, power curves and impedance spectra were generated at 70%, 60% and 50% relative humidity (25 cm2 active area), and compared to those obtained from a conventional 1-channel serpentine FF. It was found that the FF design, with a width scaling factor of 0.917 in the inlet and 0.925 in the outlet pattern, exhibited the best peak power out of the three designs (only 11% - 0.08 W/cm2 lower than reference serpentine FF). Results showed that a reduction of the viscous dissipation in the flow pattern was not directly linked to a PEMFC performance increase

Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries

Abstract: Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design: Prospective case-cohort study. Setting: Populations from eight European countries. Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure: Incident type 2 diabetes. Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes

Genomic microbial epidemiology is needed to comprehend the global problem of antibiotic resistance and to improve pathogen diagnosis

Contamination of waste effluent from hospitals and intensive food animal production with antimicrobial residues is an immense global problem. Antimicrobial residues exert selection pressures that influence the acquisition of antimicrobial resistance and virulence genes in diverse microbial populations. Despite these concerns there is only a limited understanding of how antimicrobial residues contribute to the global problem of antimicrobial resistance. Furthermore, rapid detection of emerging bacterial pathogens and strains with resistance to more than one antibiotic class remains a challenge. A comprehensive, sequence-based genomic epidemiological surveillance model that captures essential microbial metadata is needed, both to improve surveillance for antimicrobial resistance and to monitor pathogen evolution. Escherichia coli is an important pathogen causing both intestinal [intestinal pathogenic E. coli (IPEC)] and extraintestinal [extraintestinal pathogenic E. coli (ExPEC)] disease in humans and food animals. ExPEC are the most frequently isolated Gram negative pathogen affecting human health, linked to food production practices and are often resistant to multiple antibiotics. Cattle are a known reservoir of IPEC but they are not recognized as a source of ExPEC that impact human or animal health. In contrast, poultry are a recognized source of multiple antibiotic resistant ExPEC, while swine have received comparatively less attention in this regard. Here, we review what is known about ExPEC in swine and how pig production contributes to the problem of antibiotic resistance

The stocks and flows of nitrogen, phosphorus and potassium across a 30-year time series for agriculture in Huantai county, China

In order to improve the efficiency of nutrient use whilst also meeting projected changes in the demand for food within China, new nutrient management frameworks comprised of policy, practice and the means of delivering change are required. These frameworks should be underpinned by systemic analyses of the stocks and flows of nutrients within agricultural production. In this paper, a 30-year time series of the stocks and flows of nitrogen (N), phosphorus (P) and potassium (K) are reported for Huantai county, an exemplar area of intensive agricultural production in the North China Plain. Substance flow analyses were constructed for the major crop systems in the county across the period 1983–2014. On average across all production systems between 2010 and 2014, total annual nutrient inputs to agricultural land in Huantai county remained high at 18.1 kt N, 2.7 kt P and 7.8 kt K (696 kg N ha− 1; 104 kg P ha− 1; 300 kg K ha− 1). Whilst the application of inorganic fertiliser dominated these inputs, crop residues, atmospheric deposition and livestock manure represented significant, yet largely unrecognised, sources of nutrients, depending on the individual production system and the period of time. Whilst nutrient use efficiency (NUE) increased for N and P between 1983 and 2014, future improvements in NUE will require better alignment of nutrient inputs and crop demand. This is particularly true for high-value fruit and vegetable production, in which appropriate recognition of nutrient supply from sources such as manure and from soil reserves will be required to enhance NUE. Aligned with the structural organisation of the public agricultural extension service at county-scale in China, our analyses highlight key areas for the development of future agricultural policy and farm advice in order to rebalance the management of natural resources from a focus on production and growth towards the aims of efficiency and sustainability