‘I’m sorry, do I know you?' : the REDS guide to networking for academics by academics

This guide is the outcome of two events ‘How to network’ and ‘Online Networks for Enterprise’, part of the REDS (Researcher Enterprise Development Salford) series of events designed to encourage and support the development of entrepreneurial and intrapreneurial skills amongst the research community at the University of Salford. The sessions consisted of postgraduates, early career researchers and experienced academics coming together to discuss and debate the how’s, what’s, where’s, when’s and why’s of networking in academia. What we all agreed on was that networking, when done right, can lead to some brilliant working relationships and opportunities for collaborations, not to forget employment

Train High Eat Low for Osteoarthritis study (THE LO study) : protocol for a randomized controlled trial

Introduction: Osteoarthritis (OA) is one of the most prevalent chronic conditions among older adults, with the medial tibio-femoral joint being most frequently affected. The knee adduction moment is recognized as a surrogate measure of the medial tibio-femoral compartment joint load and therefore represents a valid intervention target.This article provides the rationale and methodology for THE LO study (Train High, Eat Low for Osteoarthritis), which is a randomized controlled trial that is investigating the effects of a unique, targeted lifestyle intervention in overweight/obese adults with symptomatic medial knee OA. Research question: Compared to a control group given only lifestyle advice, do the effects of the following interventions result in significant reductions in the knee adduction moment: (1) gait retraining; and (2) combined intervention (which involves a combination of three interventions: (a) gait retraining, (b) high-intensity progressive resistance training, and (c) high-protein/low-glycaemic-index energy-restricted diet)? It is hypothesized that the combined intervention group will be superior to the isolated interventions of the high-protein/low-glycaemic-index diet group and the progressive resistance training group. Finally, it is hypothesized that the combined intervention will result in a greater range of improvements in secondary outcomes, including: muscle strength, functional status, body composition, metabolic profile, and psychological wellbeing, compared to any of the isolated interventions or control group. Design: Single-blinded, randomized controlled trial adhering to the CONSORT guidelines on conduct and reporting of non-pharmacological clinical trials. Participants: One hundred and twenty-five community-dwelling people are being recruited. Inclusion criteria include: medial knee OA, low physical activity levels, no current resistance training, body mass index ≥ 25kg/m2 and age ≥ 40 years. Intervention and control: The participants are stratified by sex and body mass index, and randomized into one of five groups: (1) gait retraining; (2) progressive resistance training; (3) high-protein/low-glycaemic-index energy-restricted diet (25 to 30% of energy from protein, 45% of energy from carbohydrates, < 30% of energy from fat, and glycaemic index diet value < 50); (4) a combination of these three active interventions; or (5) a lifestyle-advice control group. All participants receive weekly telephone checks for health status, adverse events and optimisation of compliance. Measurements: Outcomes are measured at baseline, 6 and 12 months. The primary outcome is the peak knee adduction moment during the early stance phase of gait. The secondary outcome measures are both structural (radiological), with longitudinal reduction in medial minimal joint space width at 12 months, and clinical, including: change in body mass index; joint pain, stiffness and function; body composition; muscle strength; physical performance/mobility; nutritional intake; habitual physical activity and sedentary behaviour; sleep quality; psychological wellbeing and quality of life. Discussion: THE LO study will provide the first direct comparison of the long-term benefits of gait retraining, progressive resistance training and a high-protein/low-glycaemic-index energy-restricted diet, separately and in combination, on joint load, radiographic progression, symptoms, and associated co-morbidities in overweight/obese adults with OA of the knee

A novel soil manganese mechanism drives plant species loss with increased nitrogen deposition in a temperate steppe

Loss of plant diversity with increased anthropogenic nitrogen (N) deposition in grasslands has occurred globally. In most cases, competitive exclusion driven by pre-emption of light or space is invoked as a key mechanism. Here, we provide evidence from a 9-yr N-addition experiment for an alternative mechanism: differential sensitivity of forbs and grasses to increased soil manganese (Mn) levels. In Inner Mongolia steppes, increasing the N supply shifted plant community composition from grass-forb codominance (primarily Stipa krylovii and Artemisia frigida, respectively) to exclusive dominance by grass, with associated declines in overall species richness. Reduced abundance of forbs was linked to soil acidification that increased mobilization of soil Mn, with a 10-fold greater accumulation of Mn in forbs than in grasses. The enhanced accumulation of Mn in forbs was correlated with reduced photosynthetic rates and growth, and is consistent with the loss of forb species. Differential accumulation of Mn between forbs and grasses can be linked to fundamental differences between dicots and monocots in the biochemical pathways regulating metal transport. These findings provide a mechanistic explanation for N-induced species loss in temperate grasslands by linking metal mobilization in soil to differential metal acquisition and impacts on key functional groups in these ecosystems

Neuropeptide Y attenuates stress-induced bone loss through suppression of noradrenaline circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress-induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress-induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6-week restraint, or cold-stress protocol, Npy-null mice exhibit three-fold greater bone loss compared to wild-type mice, owing to suppression of osteoblast activity. This stress-protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin-releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy-null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy-null mice blocks the increase in circulating noradrenaline and the stress-induced bone loss. Thus, NPY protects against excessive stress-induced bone loss, through Y2 receptor-mediated modulation of central and peripheral noradrenergic neurons

High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis

Aims High-throughput metabolite quantification holds promise for cardiovascular risk assessment. Here, we evaluated whether metabolite quantification by nuclear magnetic resonance (NMR) improves prediction of subclinical atherosclerosis in comparison to conventional lipid testing. Methods and resultsCirculating lipids, lipoprotein subclasses, and small molecules were assayed by NMR for 1595 individuals aged 2439 years from the population-based Cardiovascular Risk in Young Finns Study. Carotid intimamedia thickness (IMT), a marker of subclinical atherosclerosis, was measured in 2001 and 2007. Baseline conventional risk factors and systemic metabolites were used to predict 6-year incidence of high IMT (<90th percentile) or plaque. The best prediction of high intimamedia thickness was achieved when total and HDL cholesterol were replaced by NMR-determined LDL cholesterol and medium HDL, docosahexaenoic acid, and tyrosine in prediction models with risk factors from the Framingham risk score. The extended prediction model improved risk stratification beyond established risk factors alone; area under the receiver operating characteristic curve 0.764 vs. 0.737, P=0.02, and net reclassification index 17.6, P=0.0008. Higher docosahexaenoic acid levels were associated with decreased risk for incident high IMT (odds ratio: 0.74; 95 confidence interval: 0.670.98; P=0.007). Tyrosine (1.33; 1.101.60; P=0.003) and glutamine (1.38; 1.131.68; P=0.001) levels were associated with 6-year incident high IMT independent of lipid measures. Furthermore, these amino acids were cross-sectionally associated with carotid IMT and the presence of angiographically ascertained coronary artery disease in independent populations. ConclusionHigh-throughput metabolite quantification, with new systemic biomarkers, improved risk stratification for subclinical atherosclerosis in comparison to conventional lipids and could potentially be useful for early cardiovascular risk assessment

Circadian rhythms have significant effects on leaf-to-canopy scale gas exchange under field conditions

Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO2 and H2O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron. Canopy and leaf-level fluxes were constantly monitored under field-like environmental conditions, and under constant environmental conditions (no variation in temperature, radiation, or other environmental cues)

Comparison of Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) for breast target volume delineation in prone and supine positions

Purpose/Objective(s): MRI provides no ionizing radiation dose (allowing inter and intra fraction imaging), improved soft tissue contrast and potentially improved conformity in delineation than CT. This study aimed to determine if T2 weighted magnetic resonance imaging improves seroma cavity (SC) and Whole Breast (WB) inter-observer conformity for radiotherapy purposes compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials: Eleven observers (two Radiologists and nine Radiation Oncologists) delineated SC and WB Clinical Target Volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer’s volumes were compared using the Dice Similarity Coefficient (DSC), Volume overlap Index (VOI), Centre of Mass (COM) shift and Hausdorff Distances (HD). An average Cavity Visualization Score (CVS) was also determined. Results: Imaging modality did not affect inter-observer variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than Supine CTVs (on both MRI and CT). SC volumes were larger on CT than MRI. SC volumes proved to be comparable in inter-observer conformity in both modalities (VOI of 0.57±0.03 for CT supine, 0.52±0.04 for MR supine, 0.56±0.03 for CT prone and 0.55±0.04 for MR prone) however after registering modalities together the inter-modality variation (DSC of 0.41±0.05 for supine and 0.38±0.04 for prone) was larger than the inter-observer variability for SC despite the location typically remaining constant. Conclusions: MRI inter-observer variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Whilst the CVS and inter-observer concordance was not significantly higher for MRI than CT, the SCs were smaller on MRI, potentially due to clearer SC definition, especially on T2-weighted MR images

MicroRNA-related DNA repair/cell-cycle genes independently associated with relapse after radiation therapy for early breast cancer

Purpose: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo. Methods and Materials: With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series of 458 patients treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage breast cancer patients, treated with adjuvant radiation therapy, with >10 years of follow-up, were analyzed. The expression of putative microRNA target biomarkers - TOP2A, POLQ, RAD54L, SKP2, PLK2, and RAG1 - were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. Results: We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as lymphovascular invasion) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of RAD54L, TOP2A, POLQ, and SKP2 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low RAG1 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, RAD54L, SKP2, and PLK2 may be predictive, being prognostic in radiation therapy-treated patients but not in untreated matched control individuals (n=107; P<.05). Conclusions: Biomarkers of DNA repair and cell cycle control can identify patients at high risk of treatment failure in those receiving radiation therapy for early breast cancer in independent cohorts. These should be further investigated prospectively, especially TOP2A and SKP2, for which targeted therapies are available