Human Nerve Growth Factor Protects Common Marmosets against Autoimmune Encephalomyelitis by Switching the Balance of T Helper Cell Type 1 and 2 Cytokines within the Central Nervous System

Multiple sclerosis is a demyelinating disorder of the central nervous system (CNS), in which an immune attack directed against myelin constituents causes myelin destruction and death of oligodendrocytes, the myelin-producing cells. Here, the efficacy of nerve growth factor (NGF), a growth factor for neurons and oligodendrocytes, in promoting myelin repair was evaluated using the demyelinating model of experimental allergic encephalomyelitis (EAE) in the common marmoset. Surprisingly, we found that NGF delayed the onset of clinical EAE and, pathologically, prevented the full development of EAE lesions. We demonstrate by immunocytochemistry that NGF exerts its antiinflammatory effect by downregulating the production of interferon γ by T cells infiltrating the CNS, and upregulating the production of interleukin 10 by glial cells in both inflammatory lesions of EAE and normal-appearing CNS white matter. Thus, NGF, currently under investigation in human clinical trials as a neuronal trophic factor, may be an attractive candidate for therapy of autoimmune demyelinating disorders

LOFAR/H-ATLAS: The low-frequency radio luminosity - star-formation rate relation

Radio emission is a key indicator of star-formation activity in galaxies, but the radio luminosity-star formation relation has to date been studied almost exclusively at frequencies of 1.4 GHz or above. At lower radio frequencies the effects of thermal radio emission are greatly reduced, and so we would expect the radio emission observed to be completely dominated by synchrotron radiation from supernova-generated cosmic rays. As part of the LOFAR Surveys Key Science project, the Herschel-ATLAS NGP field has been surveyed with LOFAR at an effective frequency of 150 MHz. We select a sample from the MPA-JHU catalogue of SDSS galaxies in this area: the combination of Herschel, optical and mid-infrared data enable us to derive star-formation rates (SFRs) for our sources using spectral energy distribution fitting, allowing a detailed study of the low-frequency radio luminosity--star-formation relation in the nearby Universe. For those objects selected as star-forming galaxies (SFGs) using optical emission line diagnostics, we find a tight relationship between the 150 MHz radio luminosity ($L_{150}$) and SFR. Interestingly, we find that a single power-law relationship between $L_{150}$ and SFR is not a good description of all SFGs: a broken power law model provides a better fit. This may indicate an additional mechanism for the generation of radio-emitting cosmic rays. Also, at given SFR, the radio luminosity depends on the stellar mass of the galaxy. Objects which were not classified as SFGs have higher 150-MHz radio luminosity than would be expected given their SFR, implying an important role for low-level active galactic nucleus activity.Comment: 21 pages, 12 figures, accepted for publication in MNRA

Time trends and geographical variation in prescribing of drugs for diabetes in England from 1998 to 2017

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAIMS: UK guidelines for type II diabetes leave the choice of glucose lowering therapies after metformin largely to prescribers. They vary greatly in cost, and comparative effectiveness data is lacking. We set out to measure the variation in prescribing of these second-line non-insulin diabetes drugs. MATERIALS AND METHODS: We evaluated time trends 1998-2016, using England's publicly available prescribing datasets, and stratified by the order prescribed to patients using the Clinical Practice Research Datalink (CPRD). We calculated the proportion of each class of diabetes drug as a percentage of the total per year. We evaluated geographical variation in prescribing using general practice-level data for the latest 12-months (to August 2017), with aggregation to Clinical Commissioning Groups (CCGs). We calculated percentiles, ranges and plotted maps. RESULTS: Prescribing of therapy after metformin is changing rapidly. DPP4-inhibitor use has increased markedly, now the most common second-line drug (43% prescriptions in 2016). Use of SGLT-2 inhibitors also increased rapidly (14% new second-line, 27% new third-line prescriptions in 2016). There is wide geographical variation in choice of therapies and average spend per patient. In contrast, metformin is consistently used first-line in accordance with guidelines. CONCLUSIONS: In England there is extensive geographical variation in the prescribing of diabetes drugs after metformin, and increasing use of higher-cost DPP4-inhibitors and SGLT-2 inhibitors over low-cost sulfonylureas. Our findings strongly support the case for comparative effectiveness trials of current diabetes drugs