School principals as promoters of education for sustainable development. Report on the research project “Lead4ESD Principal Study”

Schulleitungen üben entscheidenden Einfluss auf Schulkultur oder Leistung einer Schule aus. Ihre Rolle bei der Implementation von Bildung für nachhaltige Entwicklung (BNE) wurde bisher jedoch kaum untersucht. Der Bericht gibt Einblick in ein Forschungsprojekt zu Aktivitäten, Kompetenzen und Einfluss von Schulleitungen im Kontext von Schulentwicklung für BNE. (DIPF/Orig.)Principals exert decisive influence regarding culture or performance of a school. Their role in the implementation of Education for Sustainable Development (ESD), however, has rarely been investigated so far. The report gives an insight into a research project on activities, competencies and influence of school leaders in the context of school development for ESD. (DIPF/Orig.

Wave Energy

Part of the immense solar energy input to the earth is converted by natural processes into energy associated with ocean waves. The geographical location of the United Kingdom renders it one of the world ' s most favoured countries with respect to the potential availability of wave energy. In principle. the waves reaching our coastal waters from the North Atlantic might satisfy a considerable fraction of our electricity demand provided that reasonably high overall conversion efficiencies can be achieved . Inventors have recognised the power of the sea for many decades. and there has been no lack of ideas on how it might be tapped . But none of the ideas was developed on a substantial scale. since ample and relatively cheap supplies of other resources were always available . In recent years. however. there has been a growing recognition that--on a world scale-the presently used forms of energy may become too expensive,. too scarce or otherwise unavailable to meet our energy needs by themselves . The Government's responsibility is to ensure that as wide a range as possible of energy supply options are available when they may be needed . Research and development can provide the necessary technical and econom i c data on which the ultimate choices can be made . Within this context. the Government announced in 197 6 the start of an R and D programme on wave energy for which the first phase was to be a feasibility study lasting for two years. The funding level has been increased twice since that time to maintain the momentum of the programme in the light of technical progress . The programme has had three main components: -exploratory deve lopment of several different engineering concepts of wave energy converter; -supporting research in relevant engineering and scientific areas : • the collection and analysis of wave data. • analysis of the structural response to wave-induced motions. • mooring. • energy conversion and transm issi on. • environmental aspects ; -working up preliminary reference designs of full scale stations for tech nical and economic appraisal. The purpose of this paper is to review the present state of knowledge of wave energy in the light of the achievements of the first two-year phase of the programme . Development of the converters Four potential designs of converter were adopted for initial study. since the sparse data available were insufficient to enable a single concept to be chosen with confidence. Proposals for alternative concepts are received on a continuing basis and are assessed against a number of criteria: two of them have so far been added to the programme in order to explore new principles Apart from the basic technical differences the six designs differ from each other in their degree of complexity and their state of development. as described in Chapter 3 . Work on two of the designs has been advanced from laboratory wave tanks to the testing of 1 / 1 0th scale models in natural open water at Loch Ness and in the Solent. For all the designs . a combination of theoretical studies. laboratory work and engineering appraisal has clarified the factors which will prove to be the most crucial in determining which of them could be chosen for more extensive development. The programme has progressed from establishing the scientific feasibility of wave energy converters to confirming the engineering feasibility of designing and building some of the designs . In very broad terms: -the early part of the programme placed considerable emphasis on optimising the efficiency of extraction of the wave energy and proving the scientific feasibility ; -the present stage is concerned with the technical viability and is identifying the main cost centres in the designs . which can then be tackled by further R and D; -the immediate future must also place emphasis not only on the problems of construction . operation and maintenance. and on ways in which unit costs may be reduced . but also on the ability to survive in the most severe wave conditions . Whilst the technical feasibility of some types of converter has been established, we are far from the stage of recommending that a full scale generating station should be built . Of the four original concepts. no single design has yet emerged which is outstandingly better than the other designs when all factors are taken into account . The designs have changed considerably in the course of the feasibility study. and a continuing process of evol ution can be expected as in the early stages of any technical development programme. The optimum design may emerge from further changes in one of the original concepts. from a synthesis of ideas or from an alternative concept . The wave energy is distributed over a wide frequency and energy bandwidth and no des ign has yet been optimised to operate at or near peak efficiency over the whole spectrum. However, one of the new concepts introduced into the programme recently may offer significant advantages in this respect. Supporting research The extent of the available data on waves in the sea areas of primary interest is inadequate as yet for the full assessment of the resource . A start has been made in collecting and analysing new data. which will take several years to reach a satisfactory level. The results so far confirm the general point that the locations around the United Kingdom with the most abundant wave energy lie to the west of the Outer Hebrides, where several hundred km of searoom are available with average annual power levels in the range 35-60 kW / m of wavefront. The majority of the designs un der consideration are free-floating and the converters would operate on or near the water surface-- one of the most hostile environments for engineering structures . The ult imate feasibility. technical and economic . of all designs of floating converter will depend upon extensive further work on mooring and anchoring . Whilst over-designed mooring systems based on present knowledge have allowed the open water trials to proceed with the objective of gaining experience . the existing knowledge is not adequate to design cost-effective mooring systems which will ensure survival at full scale under storm conditions . Considerable progress has been made in assessing and under3tanding suitable energy conversion and transmission systems for the various designs of converter , but much more remains to be done to arrive at the most cost-effective solutions . The general engineering difficulties are quite basic and are related to the properties of the natural wave spectrum : -the conversion system must be able to handle large short-term variations in the instantaneous power level ; -the peak power level in the sea (of the order of 10,OOO kW /m) can be many times greater than the average power level (a few tens of kW / m) ; -the primary output is not in a form which can be handled conventionally (it is . of course . variable with time in a complex way). Moreover. apart from the randomness. other general problems arise from the low energy density of the input and the relatively low speeds and frequency of movement induced by the waves . Engineering devices to transmit large amounts of energy under such conditions must themselves be large. heavy and expensive . The efficient generation of electricity requires machinery operating at relatively high and preferably constant speed . The transition from the one regime to the other appears to be more straightforward for systems involving air turbines than for those which do not: some designs of converter may prove to be intractable in this respect. Many possible forms of energy transmission to the mainland have been reviewed . as summarised in Chapter 6 . Whilst it has been recommended that several options should be kept open in the continuing studies it is likely that most attention will be given to electricity. The overall flow of energy from the waves to a final user connected to the electricity grid involves many separate steps . each of which can involve loss of some of the energy . This can have a considerable influence on the system economics and further work in this area will need to concentrate on both reducing the number of steps and increasing the efficiency (including the directional efficiency of t he converters themselves ) of those which must remain . Unless this can be achieved the usable resource will be only a small proportion of our needs : some pointers to substantial improvements are beginning to emerge. Environmental studies have not revealed any major detrimental effects of the converters provided they are well offshore. More information is needed on the behaviour of salmon and herring off the Outer Hebrides to confirm that the fisheries would not be affected significantly by the widespread installation of converters. Concluding remarks: The costing studies of the reference designs which have been evolved so far indicate that wave-produced electricity is likely to be expensive compared with either nuclear or fossil fuels unless some major breakthrough in the engineering can be achieved . However . this does not imply that the possibility of wave energy should be abandoned at this stage . It must be emphasised that the subject is still at a very ear ly state of development and many unknown factors remain to be resolved . Under these circumstances, wave energy is best regarded at present as a possible insurance technology- the consequences of failure of one of our existing major energy supplies are so severe that it is worth paying an insurance premium to explore fully the alternatives . Nevertheless. the evidence from the feasibility study so far does not allow a recommendation for a full-scale development programme to be made at this time . Much more can be achieved to explore and then to narrow the design choices by continuing work at about the 1 / 1 0th scale coupled with . on the one hand . limited trials of some critical components at larger scale and . on the other hand . f urther creative engineering on the drawing board and laboratory work in a new generation of wave tanks (of which the forerunner has been successfully commissioned at Edinburgh University). The programme has generated a broad basis of knowledge of all aspects of wave energy which did not exist before. so that we can now identify clearly the critical problems to be tackled by further work

Using zeta-potential measurements to quantify peptide partition to lipid membranes

© The Author(s) 2011. This article is published with open access at Springerlink.com.Open Access: This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (Kp) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and ζ-potential measurements. In this work, we derived and tested a mathematical model to determine the Kp from ζ-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that ζ-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling.This work was partially supported by project PTDC/QUI/ 69937/2006 from Fundação para a Ciência e Tecnologia-Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), and by Fundação Calouste Gulbenkian (Portugal). JMF and MMD also thank FCT-MCTES for grants IMM/BT/37-2010 and SFRH/BD/41750/2007, respectively

Resistance of Foxp3+ Regulatory T Cells to Nur77-Induced Apoptosis Promotes Allograft Survival

The NR4A nuclear receptor family member Nur77 (NR4A1) promotes thymocyte apoptosis during negative selection of autoreactive thymocytes, but may also function in mature extrathymic T cells. We studied the effects of over-expression of Nur77 on the apoptosis of murine peripheral T cells, including thymic-derived Foxp3+ regulatory (Treg) cells. Overexpression of Nur77 in the T cell lineage decreased numbers of peripheral CD4 and CD8 T cells by ∼80% compared to wild-type (WT) mice. However, the proportions of Treg cells were markedly increased in the thymus (61% of CD4+Foxp3+ singly positive thymocytes vs. 8% in WT) and secondary lymphoid organs (40–50% of CD4+Foxp3+ T cells vs. 7–8% in WT) of Nur77 transgenic (Nur77Tg) mice, and immunoprecipitation studies showed Nur77 was associated with a recently identified HDAC7/Foxp3 transcriptional complex. Upon activation through the T cell receptor in vitro or in vivo, Nur77Tg T cells showed only marginally decreased proliferation but significantly increased apoptosis. Fully allogeneic cardiac grafts transplanted to Nur77Tg mice survived long-term with well-preserved structure, and recipient splenocytes showed markedly enhanced apoptosis and greatly reduced anti-donor recall responses. Allografts in Nur77Tg recipients had significantly increased expression of multiple Treg-associated genes, including Foxp3, Foxp1, Tip60 and HDAC9. Allograft rejection was restored by CD25 monoclonal antibody therapy, indicating that allograft acceptance was dependent upon Treg function in Nur77Tg recipients. These data show that compared to conventional CD4 and CD8 T cells, Foxp3+ Tregs are relatively resistant to Nur77-mediated apoptosis, and that tipping the balance between the numbers of Tregs and responder T cells in the early period post-transplantation can determine the fate of the allograft. Hence, induced expression of Nur77 might be a novel means to achieve long-term allograft survival

Alternatives to antibiotics-a pipeline portfolio review

Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future.</p

International consensus definition of low anterior resection syndrome

BACKGROUND: Low anterior resection syndrome is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The low anterior resection syndrome score was designed as a simple tool for clinical evaluation of low anterior resection syndrome. Although the low anterior resection syndrome score has good clinical utility, it may not capture all important aspects that patients may experience. OBJECTIVE: The aim of this collaboration was to develop an international consensus definition of low anterior resection syndrome that encompasses all aspects of the condition and is informed by all stakeholders. DESIGN: This international patient-provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. PARTICIPANTS: Three expert groups participated: patients, surgeons, and other health professionals from 5 regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in 3 languages (English, Spanish, and Danish). MAIN OUTCOME MEASURE: The primary outcome measured was the priorities for the definition of low anterior resection syndrome. RESULTS: Three hundred twenty-five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96%, and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to 8 symptoms and 8 consequences that capture essential aspects of the syndrome. LIMITATIONS: Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. CONCLUSIONS: This is the first definition of low anterior resection syndrome developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of low anterior resection syndrome. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in low anterior resection syndrome over time and with intervention

Impact of cross-section uncertainties on supernova neutrino spectral parameter fitting in the Deep Underground Neutrino Experiment

A primary goal of the upcoming Deep Underground Neutrino Experiment (DUNE) is to measure the $\mathcal{O}(10)$ MeV neutrinos produced by a Galactic core-collapse supernova if one should occur during the lifetime of the experiment. The liquid-argon-based detectors planned for DUNE are expected to be uniquely sensitive to the $\nu_e$ component of the supernova flux, enabling a wide variety of physics and astrophysics measurements. A key requirement for a correct interpretation of these measurements is a good understanding of the energy-dependent total cross section $\sigma(E_\nu)$ for charged-current $\nu_e$ absorption on argon. In the context of a simulated extraction of supernova $\nu_e$ spectral parameters from a toy analysis, we investigate the impact of $\sigma(E_\nu)$ modeling uncertainties on DUNE's supernova neutrino physics sensitivity for the first time. We find that the currently large theoretical uncertainties on $\sigma(E_\nu)$ must be substantially reduced before the $\nu_e$ flux parameters can be extracted reliably: in the absence of external constraints, a measurement of the integrated neutrino luminosity with less than 10\% bias with DUNE requires $\sigma(E_\nu)$ to be known to about 5%. The neutrino spectral shape parameters can be known to better than 10% for a 20% uncertainty on the cross-section scale, although they will be sensitive to uncertainties on the shape of $\sigma(E_\nu)$. A direct measurement of low-energy $\nu_e$-argon scattering would be invaluable for improving the theoretical precision to the needed level.Comment: 25 pages, 21 figure

Doping liquid argon with xenon in ProtoDUNE Single-Phase: effects on scintillation light

Doping of liquid argon TPCs (LArTPCs) with a small concentration of xenon is a technique for light-shifting and facilitates the detection of the liquid argon scintillation light. In this paper, we present the results of the first doping test ever performed in a kiloton-scale LArTPC. From February to May 2020, we carried out this special run in the single-phase DUNE Far Detector prototype (ProtoDUNE-SP) at CERN, featuring 720 t of total liquid argon mass with 410 t of fiducial mass. A 5.4 ppm nitrogen contamination was present during the xenon doping campaign. The goal of the run was to measure the light and charge response of the detector to the addition of xenon, up to a concentration of 18.8 ppm. The main purpose was to test the possibility for reduction of non- uniformities in light collection, caused by deployment of photon detectors only within the anode planes. Light collection was analysed as a function of the xenon concentration, by using the pre-existing photon detection system (PDS) of ProtoDUNE-SP and an additional smaller set-up installed specifically for this run. In this paper we first summarize our current understanding of the argon-xenon energy transfer process and the impact of the presence of nitrogen in argon with and without xenon dopant. We then describe the key elements of ProtoDUNE-SP and the injection method deployed. Two dedicated photon detectors were able to collect the light produced by xenon and the total light. The ratio of these components was measured to be about 0.65 as 18.8 ppm of xenon were injected. We performed studies of the collection efficiency as a function of the distance between tracks and light detectors, demonstrating enhanced uniformity of response for the anode-mounted PDS. We also show that xenon doping can substantially recover light losses due to contamination of the liquid argon by nitrogen

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders