Can we identify response markers to antihypertensive drugs? First results from the Ideal Trial

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.Journal of Human Hypertension advance online publication, 17 April 2014; doi:10.1038/jhh.2014.29

Satellite university campuses and economic development in peripheral regions

Satellite university campuses – whereby established universities decentralise part of their activities, often to areas previously lacking a university – contribute to the diversification of university systems. While satellite campuses, due to their small scale and limited resources, might perform some activities less efficiently than their larger parent universities, we argue that they are uniquely placed to serve the needs of their localities. Based on the case of a satellite campus in North-West Italy, we show that: (i) the campus’ main contribution lies in widening access to higher education to residents who would not attend university in the absence of local provision; (ii) the campus contributes to local development also through research and business and community engagement, and by stimulating local demand for knowledge-intensive services; (iii) research and engagement are more effective for local development where local firms possess relevant absorptive capacity and where there is a favourable institutional framework

Achievable tolerances in robotic feature machining operations using a low-cost hexapod

Portable robotic machine tools potentially allow feature machining processes to be brought to large parts in various industries, creating an opportunity for capital expenditure and operating cost reduction. However, robots lack the machining capability of conventional equipment, which ultimately results in dimensional errors in parts. This work showcases a low-cost hexapod-based robotic machine tool and presents experimental research conducted to investigate how the widely researched robotic machining challenges, e.g. structural dynamics and kinematics, translate to achievable tolerance ranges in real-world production to highlight currently feasible applications and provide a context for considering technology improvements. Machining trials assess the total dimensional errors in the final part over multiple geometries. A key finding is error variation which is in the sub-millimetre range, although, in some cases, upper tolerance limits < 100 μm are achieved. Practical challenges are also noted. Most significantly, it is demonstrated that dimensional machining error is mainly systematic in nature and therefore that the total error can be dramatically reduced with in situ measurement and compensation. Potential is therefore found to achieve a flexible, high-performance robotic machining capability despite complex and diverse underlying scientific challenges. Overall, the work presented highlights achievable tolerances in low-cost robotic machining and opportunities for improvement, also providing a practical benchmark useful for process selection

Istaroxime: a new luso-inotropic agent for heart failure

Istaroxime is a new luso-inotropic compound selected for the treatment of acute heart failure syndromes, which reduces sodium-potassium adenosine triphosphatase (ATPase) activity and stimulates the sarcoplasmic calcium ATPase isoform 2 reuptake func- tion. The aim of this study was to evaluate the safety profile of istaroxime. For this purpose, istaroxime was administered during a 24-hour infusion to conscious dogs with chronic heart failure and to genetically cardiomyopathic BIO TO.2 hamsters for 34 weeks orally. The parameters recorded were arrhythmic events and hemodynamic effects in dogs and mortality in hamsters. In dogs, istaroxime at 1, 3, and 4 g/kg per min did not trigger arrhythmic events or magnify preexisting events. It increased left ventricular (LV) dP/dtmax (about 50% at 3 g/kg per min) and LV dP/dtmax (about 20% at 3 g/kg per min) without changing heart rate, blood pressure, or double product. At 4 g/kg per min, istaroxime increased dP/dtmax >100% but induced intense emesis in all animals. In cardiomyopathic hamsters, the dose of 30 mg/kg prolonged the survival rate to 32%. In conclusion, istaroxime seems to be a promising and safe new drug for improving cardiac performance in the failing heart