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Background Many international clinical guidelines recommend therapeutic exercise as a core treatment for knee and hip osteoarthritis. We aimed to identify individual patient-level moderators of the effect of therapeutic exercise for reducing pain and improving physical function in people with knee osteoarthritis, hip osteoarthritis, or both. Methods We did a systematic review and individual participant data (IPD) meta-analysis of randomised controlled trials comparing therapeutic exercise with non-exercise controls in people with knee osteoathritis, hip osteoarthritis, or both. We searched ten databases from March 1, 2012, to Feb 25, 2019, for randomised controlled trials comparing the effects of exercise with non-exercise or other exercise controls on pain and physical function outcomes among people with knee osteoarthritis, hip osteoarthritis, or both. IPD were requested from leads of all eligible randomised controlled trials. 12 potential moderators of interest were explored to ascertain whether they were associated with short-term (12 weeks), medium-term (6 months), and long-term (12 months) effects of exercise on self-reported pain and physical function, in comparison with non-exercise controls. Overall intervention effects were also summarised. This study is prospectively registered on PROSPERO (CRD42017054049). Findings Of 91 eligible randomised controlled trials that compared exercise with non-exercise controls, IPD from 31 randomised controlled trials (n=4241 participants) were included in the meta-analysis. Randomised controlled trials included participants with knee osteoarthritis (18 [58%] of 31 trials), hip osteoarthritis (six [19%]), or both (seven [23%]) and tested heterogeneous exercise interventions versus heterogeneous non-exercise controls, with variable risk of bias. Summary meta-analysis results showed that, on average, compared with non-exercise controls, therapeutic exercise reduced pain on a standardised 0–100 scale (with 100 corresponding to

In rodent models of type 2 diabetes (T2D), central administration of FGF1 normalizes elevated blood glucose levels in a manner that is sustained for weeks or months. Increased activity of NPY/ AgRP neurons in the hypothalamic arcuate nucleus (ARC) is implicated in the pathogenesis of hyperglycemia in these animals, and the ARC is a key brain area for the antidiabetic action of FGF1. We therefore sought to determine whether FGF1 inhibits NPY/AgRP neurons and, if so, whether this inhibitory effect is sufficiently durable to offer a feasible explanation for sustained diabetes remission induced by central administration of FGF1. Here, we show that FGF1 inhibited ARC NPY/AgRP neuron activity, both after intracerebroventricular injection in vivo and when applied ex vivo in a slice preparation; we also showed that the underlying mechanism involved increased input from presynaptic GABAergic neurons. Following central administration, the inhibitory effect of FGF1 on NPY/AgRP neurons was also highly durable, lasting for at least 2 weeks. To our knowledge, no precedent for such a prolonged inhibitory effect exists. Future studies are warranted to determine whether NPY/AgRP neuron inhibition contributes to the sustained antidiabetic action elicited by intracerebroventricular FGF1 injection in rodent models of T2D.

Intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) elicits remission of diabetic hyperglycemia in rodent models of type 2 diabetes. Here, we present an optimized protocol to study the intracellular signaling pathways underlying the FGF1-induced sustained glucose lowering in the mouse brain. This protocol combines icv injection of FGF1 and osmotic mini-pump infusion of U0126, an inhibitor of MAPK/ERK signaling. We describe the surgical procedure and verification of U0126 inhibition of FGF1-stimulated hypothalamic MAPK/ERK signaling via western blot. For complete details on the use and execution of this protocol, please refer to Brown et al. (2021).

At the Protections 2018 conference, the WireWall wave overtopping research project was introduced. WireWall uses recent advances in high frequency capacitance wire technology that can measure overtopping data. Wave overtopping has now been measured in the laboratory and in the field using the WireWall system. Here we provide an update on the validation of the system in flume tests and results from the first field measurement campaign. Before deployment in the field, an extensive set of tests were carried out in one of the 2D wave flumes at HR Wallingford. These tests simulated known wave conditions from a buoy near the field measurement site, and a representation of the sea wall at the site. The structure (shown in Figure 1) underwent extensive testing and was used to validate the WireWall rig. Using traditional methods of assessing wave overtopping in the flume, the WireWall measurements were directly validated against the known volumes collected in the overtopping tanks. The WireWall field system was deployed at Crosby, Liverpool during the winter of 2018/19, where waves regularly overtop the sea wall. Comparison between the WireWall measurements and the BayonetGPE predictions for one of the Crosby deployments shows good agreement, with the predictions and the WireWall measurements being within the uncertainties estimated for the BayonetGPE predictions.

The purpose of this report is to document the communications protocol and test system osd2ERDDAP developed as part of the Enhancing Climate Observations, Models and Data (ECO MAD) project. The approach allows deployed sensors to telemeter small quantities of arbitrary tabular Ocean Science Data (osd) directly to an ERDDAP server via the Internet in a way that is more efficient for the sensor than using ERDDAP’s existing HTML Forms interface. ERDDAP is a data server that provides a simple and consistent way to download subsets of scientific datasets in common file formats and make graphs and maps. It is the online server used by the British Oceanographic Data Centre (BODC) and National Oceanic and Atmospheric Administration (NOAA) to publicly share environmental data in a format that meets international data management standards. Future use of this API with a range of ocean sensors and ERDDAP will increase the efficiency of data streaming. In turn this reduces power (and associated maintenance) requirements that is vital to deliver low-cost long-term monitoring networks, which support climate research and the management of climate impacts.