Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO):Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017.</p

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age 65 36 weeks and a birth weight 65 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017

Open innovation and solar photovoltaic development acceleration

Today, technology and innovation management are inseparable connected with open innovation due to increased technological complexity and shorter product lifecycles. Many companies realise that valuable ideas do not only come from the inside of the organisation but many experts around the world can have valuable ideas for these companies. Different organisations in high technology industries use open innovation models to exploit and explore ideas from outside the company boundaries. Solar PV as one of the electricity sources for the future, could especially reduce GHG emissions, secure energy security and economic growth, but needs to become cheaper to compete with conventional electricity sources. Currently there are many limitations in the solar PV innovation process such as narrow programs, poor co-ordination across organisation boundaries and lack in knowledge distribution. Therefore, this report will follow the research question if open innovation can have accelerating effects on the technology development in the solar PV industry. The aim is to set up a causal loop model following the principles of system dynamics to understand the complex innovation system. By using a literature review to understand the solar PV industry better and two case studies from large technology companies (Evonik Industries AG and Siemens AG) the variables and feedbacks for the model were identified. The model was developed to address the current limitations of the solar PV innovation process. A positive feedback loop additional to the innovation process of the solar PV was identified. It is developing technology and business but also filling knowledge gaps by collaborating with universities and other large and small size organisations aiming at every phase of the innovation process. Open innovation looks at the business model as a whole not purely at technology development. Evonik showed how ideas that are out of scope of the main business become part of the company to tap into new markets. Siemens developed a virtual collaboration community to solve problems faster and avoid double R&D efforts. One negative loop was discovered that will slow down the development process, caused by organisational culture shock and resource intensive open innovation programs to set up both virtual and physical infrastructure. Open innovation seems inevitable to increase development in the area of solar PV especially when pursuing radical innovation that come from the intersections between industries and therefore might have accelerating effects on the technology, but also business development in the industry. Further research is necessary to quantify the causal loop model, to simulate the system and further test it in practice

Sommerferien auf dem Lande

SOMMERFERIEN AUF DEM LANDE Sommerferien auf dem Lande ( - ) Cover ( - ) Endsheet ( - ) Prepage ( - ) Image ( - ) Title page ( - ) Inhalt ( - ) 1. Ferien (5) 2. Zigeuner (13) 3. Im Walde (21) 4. Entdeckungen (28) Image ( - ) 5. Regentage (37) 6. Beim Schäfer (43) 7. Im Gebirge (63) Image ( - ) 8. Der Flachs ist reif (78) Image ( - ) 9. Einfahren (87) 10. Ferienende (94) Endsheet ( - ) Cover ( -