Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy

AbstractLower blood oxygenation level dependent (BOLD) signal changes in response to a visual stimulus in functional magnetic resonance imaging (fMRI) have been observed in cross-sectional studies of cerebral amyloid angiopathy (CAA), and are presumed to reflect impaired vascular reactivity. We used fMRI to detect a longitudinal change in BOLD responses to a visual stimulus in CAA, and to determine any correlations between these changes and other established biomarkers of CAA progression. Data were acquired from 22 patients diagnosed with probable CAA (using the Boston Criteria) and 16 healthy controls at baseline and one year. BOLD data were generated from the 200 most active voxels of the primary visual cortex during the fMRI visual stimulus (passively viewing an alternating checkerboard pattern). In general, BOLD amplitudes were lower at one year compared to baseline in patients with CAA (p=0.01) but were unchanged in controls (p=0.18). The longitudinal difference in BOLD amplitudes was significantly lower in CAA compared to controls (p<0.001). White matter hyperintensity (WMH) volumes and number of cerebral microbleeds, both presumed to reflect CAA-mediated vascular injury, increased over time in CAA (p=0.007 and p=0.001, respectively). Longitudinal increases in WMH (rs=0.04, p=0.86) or cerebral microbleeds (rs=−0.18, p=0.45) were not associated with the longitudinal decrease in BOLD amplitudes

Mapping interactions between the sustainable development goals: lessons learned and ways forward

Pursuing integrated research and decision-making to advance action on the sustainable development goals (SDGs) fundamentally depends on understanding interactions between the SDGs, both negative ones (“trade-offs”) and positive ones (“co-benefits”). This quest, triggered by the 2030 Agenda, has however pointed to a gap in current research and policy analysis regarding how to think systematically about interactions across the SDGs. This paper synthesizes experiences and insights from the application of a new conceptual framework for mapping and assessing SDG interactions using a defined typology and characterization approach. Drawing on results from a major international research study applied to the SDGs on health, energy and the ocean, it analyses how interactions depend on key factors such as geographical context, resource endowments, time horizon and governance. The paper discusses the future potential, barriers and opportunities for applying the approach in scientific research, in policy making and in bridging the two through a global SDG Interactions Knowledge Platform as a key mechanism for assembling, systematizing and aggregating knowledge on interactions

The disequilibrium of hope: A grounded theory analysis of parents' experiences of receiving a “no primary finding” result from genome sequencing

Genome sequencing (GS) has the potential to reduce the “diagnostic odyssey” that many parents of children with rare undiagnosed conditions experience. While much research has considered the impact of receiving a diagnostic result, research has rarely focused solely on the impact of receiving a “no primary finding” (NPF) result. This study aimed to investigate the experience of parents of children with rare and undiagnosed conditions following an NPF result from GS. Nine parents whose child had an NPF result from GS were recruited through the social media platform of the charity SWAN (Syndromes Without A Name) UK. Semi-structured telephone interviews were conducted, transcribed verbatim, and analyzed using grounded theory. Analysis led to the emergence of two main themes. The first theme “Striving to Solve the Unsolved Puzzle” concerned the experience of striving to end the “diagnostic odyssey.” The second theme “Navigating Hope, Lost then Found” plots the trajectory of hope raised by the promise of a new technology, dashed by the NPF, and the eventual return of small and distant hope for the future. Taken together, these themes allowed for a proposed theory: “The Disequilibrium of Hope,” which highlights the dynamic and modifiable experience of hope participants experience in their GS journey. These results suggest GS can be an emotional rollercoaster for parents. While hope plays an important role in coping with the day-to-day life of living with a rare disease, careful management of expectations from GS is important during pre-test counseling, and continued follow-up and support are needed beyond result disclosure. An understanding of the disappointment and distress caused by an NPF result is valuable for healthcare professionals in this field to ensure counseling can be tailored. Further research should consider how to support parents after an NPF result

Education for sustainable development: A study in adolescent perception changes towards sustainability following a strategic planning-based intervention-the young persons' plan for the planet program

© 2019 by the authors. In 2016, the United Nations (UN) launched the 17 Sustainable Development Goals (SDGs) as a framework for sustainable development and a sustainable future. However, the global challenge has been to engage, connect, and empower communities, particularly young people, to both understand and deliver the 17 SDGs. In this study, we show the benefit of a strategic planning-based experiential learning tool, the Young Persons' Plan for the Planet (YPPP) Program, to improve the underlying competencies of Australian and Mauritian adolescents in increasing understanding and delivering the SDGs. The study was conducted with 300 middle to senior high school students, in 25 schools throughout Australia and Mauritius, over an 18-month period. The intervention included the development of research, strategic planning, management, STEM (Science Technology, Engineering, Maths) and global competency skills in the students, to enable them to build and deliver regional and national SDG plans. Research methods included pre- and post-intervention testing of the attitudes of these students to sustainable development outcomes and compared these attitudes to subsets of scientists and the Australian national population. Our results, from both qualitative and quantitative evidence, demonstrate significant improvements in these adolescents' appreciation of, and attitudes towards, the SDGs and sustainable outcomes, across a range of key parameters. The results from the 76 students who attended the International Conference in Mauritius in December 2018 demonstrate significant improvements in mean levels of understanding, and attitudes of the students towards the SDGs awareness (+85%), understanding/engagement (+75%), motivation (+57%), and action orientation/empowerment (+66%). These changes were tested across a range of socio-demographic, geographic, and cultural parameters, with consistent results. These findings have significant implications for the challenge of sustainable education and achieving community engagement and action towards the SDGs in Australia and Mauritius, particularly for young people. As the intervention can be replicated and scaled, the findings also highlight the opportunity to extend both the research and this type of experiential learning intervention across both broader geographies and other generation and community segments

Reconceptualising adaptation to climate change as part of pathways of change and response

The need to adapt to climate change is now widely recognised as evidence of its impacts on social and natural systems grows and greenhouse gas emissions continue unabated. Yet efforts to adapt to climate change, as reported in the literature over the last decade and in selected case studies, have not led to substantial rates of implementation of adaptation actions despite substantial investments in adaptation science. Moreover, implemented actions have been mostly incremental and focused on proximate causes; there are far fewer reports of more systemic or transformative actions. We found that the nature and effectiveness of responses was strongly influenced by framing. Recent decision-oriented approaches that aim to overcome this situation are framed within a "pathways" metaphor to emphasise the need for robust decision making within adaptive processes in the face of uncertainty and inter-temporal complexity. However, to date, such "adaptation pathways" approaches have mostly focused on contexts with clearly identified decision-makers and unambiguous goals; as a result, they generally assume prevailing governance regimes are conducive for adaptation and hence constrain responses to proximate causes of vulnerability. In this paper, we explore a broader conceptualisation of "adaptation pathways" that draws on 'pathways thinking' in the sustainable development domain to consider the implications of path dependency, interactions between adaptation plans, vested interests and global change, and situations where values, interests, or institutions constrain societal responses to change. This re-conceptualisation of adaptation pathways aims to inform decision makers about integrating incremental actions on proximate causes with the transformative aspects of societal change. Case studies illustrate what this might entail. The paper ends with a call for further exploration of theory, methods and procedures to operationalise this broader conceptualisation of adaptation

Intelligence within BAOR and NATO's Northern Army Group

During the Cold War the UK's principal military role was its commitment to the North Atlantic Treaty Organisation (NATO) through the British Army of the Rhine (BAOR), together with wartime command of NATO's Northern Army Group. The possibility of a surprise attack by the numerically superior Warsaw Pact forces ensured that great importance was attached to intelligence, warning and rapid mobilisation. As yet we know very little about the intelligence dimension of BAOR and its interface with NATO allies. This article attempts to address these neglected issues, ending with the impact of the 1973 Yom Kippur War upon NATO thinking about warning and surprise in the mid-1970s. It concludes that the arrangements made by Whitehall for support to BAOR from national assets during crisis or transition to war were - at best - improbable. Accordingly, over the years, BAOR developed its own unique assets in the realm of both intelligence collection and special operations in order to prepare for the possible outbreak of conflict

ICRPfinder: a fast pattern design algorithm for coding sequences and its application in finding potential restriction enzyme recognition sites

<p>Abstract</p> <p>Background</p> <p>Restriction enzymes can produce easily definable segments from DNA sequences by using a variety of cut patterns. There are, however, no software tools that can aid in gene building -- that is, modifying wild-type DNA sequences to express the same wild-type amino acid sequences but with enhanced codons, specific cut sites, unique post-translational modifications, and other engineered-in components for recombinant applications. A fast DNA pattern design algorithm, ICRPfinder, is provided in this paper and applied to find or create potential recognition sites in target coding sequences.</p> <p>Results</p> <p>ICRPfinder is applied to find or create restriction enzyme recognition sites by introducing silent mutations. The algorithm is shown capable of mapping existing cut-sites but importantly it also can generate specified new unique cut-sites within a specified region that are guaranteed not to be present elsewhere in the DNA sequence.</p> <p>Conclusion</p> <p>ICRPfinder is a powerful tool for finding or creating specific DNA patterns in a given target coding sequence. ICRPfinder finds or creates patterns, which can include restriction enzyme recognition sites, without changing the translated protein sequence. ICRPfinder is a browser-based JavaScript application and it can run on any platform, in on-line or off-line mode.</p

Aharonov-Bohm Oscillations in a One-Dimensional Wigner Crystal-Ring

We calculate the magnetic moment (`persistent current') in a strongly correlated electron system --- a Wigner crystal --- in a one-dimensional ballistic ring. The flux and temperature dependence of the persistent current in a perfect ring is shown to be essentially the same as for a system of non-interacting electrons. In contrast, by incorporating into the ring geometry a tunnel barrier that pins the Wigner crystal, the current is suppressed and its temperature dependence is drastically changed. The competition between two temperature effects --- the reduced barrier height for macroscopic tunneling and loss of quantum coherence --- may result in a sharp peak in the temperature dependence. The character of the macroscopic quantum tunneling of a Wigner crystal ring is dictated by the strength of pinning. At strong pinning the tunneling of a rigid Wigner crystal chain is highly inhomogeneous, and the persistent current has a well-defined peak at $T\sim 0.5\ \hbar s/L$ independent of the barrier height ($s$ is the sound velocity of the Wigner crystal, $L$ is the length of the ring). In the weak pinning regime, the Wigner crystal tunnels through the barrier as a whole and if $V_p>T_0$ the effect of the barrier is to suppress the current amplitude and to shift the crossover temperature from $T_0$ to $T^*\simeq \sqrt{V_{p}T_{0}}$. ($V_{p}$ is the amplitude of the pinning potential, $T_{0} =\hbar v_{F}/L ,\; v_{F}\sim \hbar/ma$ is the drift velocity of a Wigner crystal ring with lattice spacing $a$). For very weak pinning, $V_p\ll T_0$, the influence of the barrier on the persistent current of a Wigner crystal ring is negligibly small.Comment: 30 pages, RevTeX, 2 figures available on reques

On the modelling of infilled RC frames through strut models

Infill panels largely affect the seismic response of framed constructions. The wide variety in their mechanical and geometrical features has produced many different models and assumptions in their analytical representation. In this paper the simplest and most diffuse analytical approach, based on the introduction of equivalent struts, has been checked. An overview is presented, focusing on the strut dimensions, strength and number. Two case-studies, taken by two different experimental campaigns, have been considered and reproduced. The obtained results have been compared to the experimental ones, and some parameters have been checked for selecting the model to use for analysis