A LOFAR census of non-recycled pulsars: average profiles, dispersion measures, flux densities, and spectra

We present first results from a LOFAR census of non-recycled pulsars. The census includes almost all such pulsars known (194 sources) at declinations Dec > 8 and Galactic latitudes jGbj > 3, regardless of their expected flux densities and scattering times. Each pulsar was observed for 20 min in the contiguous frequency range of 110-188 MHz. Full-Stokes data were recorded. We present the dispersion measures, flux densities, and calibrated total intensity profiles for the 158 pulsars detected in the sample. The median uncertainty in census dispersion measures (1:5 × 10-3 pc cm-3) is ten times smaller, on average, than in the ATNF pulsar catalogue. We combined census flux densities with those in the literature and fitted the resulting broadband spectra with single or broken power-law functions. For 48 census pulsars such fits are being published for the first time. Typically, the choice between single and broken power-laws, as well as the location of the spectral break, were highly influenced by the spectral coverage of the available flux density measurements. In particular, the inclusion of measurements below 100MHz appears essential for investigating the lowfrequency turnover in the spectra for most of the census pulsars. For several pulsars, we compared the spectral indices from different works and found the typical spread of values to be within 0.5-1.5, suggesting a prevailing underestimation of spectral index errors in the literature. The census observations yielded some unexpected individual source results, as we describe in the paper. Lastly, we will provide this unique sample of wide-band, low-frequency pulse profiles via the European Pulsar Network Database

Blood pressure reduction in diabetes: Lessons from ACCORD, SPRINT and EMPA-REG OUTCOME

In patients with diabetes mellitus, the presence of hypertension substantially increases the risk of cardiovascular events, and reductions in blood pressure (BP) can reduce cardiovascular morbidity and mortality. Following evidence from trials randomizing patients to diastolic BP levels, previous guidelines recommended an office BP target of <130/80 mmHg in individuals with diabetes mellitus. However, the evidence for this systolic BP (SBP) target was derived from observational studies. When the results of the ACCORD-BP study showed that those individuals with diabetes mellitus and a target BP of <120 mmHg had a cardiovascular risk that is similar to those with <140 mmHg, all guidelines returned to a recommended SBP of <140 mmHg. However, the ACCORD-BP trial was limited by the low number of cardiovascular events observed, whereas the mean SBP in the 'conventional' arm was 133 mmHg. The SPRINT study, showing cardiovascular benefits in hypertensive patients without diabetes mellitus randomized to SBP <120 mmHg versus those randomized to <140 mmHg, came in contrast with the ACCORD-BP, but a detailed evaluation reveals many similarities between the two trials. Finally, the EMPA-REG OUTCOME study, with impressive cardiovascular mortality reduction with empagliflozin, suggested that reduction of SBP to around 130 mmHg is safe and might explain part of these beneficial results. In this Review, we evaluate the implications of the ACCORD-BP, SPRINT and EMPA-REG OUTCOME trials and previous studies for the optimal BP target in diabetes mellitus.Sin financiación20.265 JCR (2017) Q1, 2/143 Endocrinology and MetabolismUE

PPAR alpha: an emerging therapeutic target in diabetic microvascular damage

The global pandemic of diabetes mellitus portends an alarming rise in the prevalence of microvascular complications, despite advanced therapies for hyperglycemia, hypertension and dyslipidemia. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is expressed in organs affected by diabetic microvascular disease (retina, kidney and nerves), and its expression is regulated specifically in these tissues. Experimental evidence suggests that PPAR alpha activation attenuates or inhibits several mediators of vascular damage, including lipotoxicity, inflammation, reactive oxygen species generation, endothelial dysfunction, angiogenesis and thrombosis, and thus might influence intracellular signaling pathways that lead to microvascular complications. PPAR alpha has emerged as a novel target to prevent microvascular disease, via both its lipid-related and lipid-unrelated actions. Despite strong experimental evidence of the potential benefits of PPAR alpha agonists in the prevention of vascular damage, the evidence from clinical studies in patients with diabetes mellitus remains limited. Promising findings from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study on microvascular outcomes are countered by elevations in participants' homocysteine and creatinine levels that might potentially attenuate the benefits of PPAR alpha activation. This Review focuses on the role of PPAR alpha activation in diabetic microvascular disease and highlights the available experimental and clinical evidence from studies of PPAR alpha agonists