Identifying robust response options to manage environmental change using an ecosystem approach:a stress-testing case study for the UK

A diverse range of response options was evaluated in terms of their utility for sustaining ecosystem services in the UK. Robustness of response options was investigated by applying a ‘stress-testing’ method which evaluated expected performance against combined scenarios of socioeconomic and climate change. Based upon stakeholder feedback, a reference scenario representing current trends in climate and socioeconomic drivers (‘business-as-usual’) was used as a dynamic baseline against which to compare results of other scenarios. The robustness of response options was evaluated by their utility in different environmental and social contexts as represented by the scenarios, and linked to their adaptability to adjust to changing conditions. Key findings demonstrate that adaptability becomes increasingly valuable as the magnitude and rate of future change diverges from current trends. Stress-testing also revealed that individual responses in isolation are unlikely to be robust meaning there are advantages from integrating cohesive combinations (bundles) of response options to maximise their individual strengths and compensate for weaknesses. This identifies a role for both top-down and bottom-up responses, including regulation, spatial targeting, incentives and partnership initiatives, and their use in combination through integrated assessment and planning consistent with the adoption of an Ecosystem Approach. Stress-testing approaches can have an important role in future-proofing policy appraisals but important knowledge gaps remain, especially for cultural and supporting ecosystem services. Finally, barriers and enablers to the implementation of more integrated long-term adaptive responses were identified drawing on the ‘4 Is’ (Institutions, Information, Incentives, Identity) conceptual framework. This highlighted the crucial but usually understated role of identity in promoting ownership and uptake of responses

A framework for assessing and implementing the co-benefits of nature-based solutions in urban areas

To address challenges associated with climate resilience, health and well-being in urban areas, current policy platforms are shifting their focus from ecosystem-based to nature-based solutions (NBS), broadly defined as solutions to societal challenges that are inspired and supported by nature. NBS result in the provision of co-benefits, such as the improvement of place attractiveness, of health and quality of life, and creation of green jobs. Few frameworks exist for acknowledging and assessing the value of such co-benefits of NBS and to guide cross-sectoral project and policy design and implementation. In this paper, we firstly developed a holistic framework for assessing co-benefits (and costs) of NBS across elements of socio-cultural and socio-economic systems, biodiversity, ecosystems and climate. The framework was guided by a review of over 1700 documents from science and practice within and across 10 societal challenges relevant to cities globally. We found that NBS can have environmental, social and economic co-benefits and/or costs both within and across these 10 societal challenges. On that base, we develop and propose a seven-stage process for situating co-benefit assessment within policy and project implementation. The seven stages include: 1) identify problem or opportunity; 2) select and assess NBS and related actions; 3) design NBS implementation processes; 4) implement NBS; 5) frequently engage stakeholders and communicate co-benefits; 6) transfer and upscale NBS; and 7) monitor and evaluate co-benefits across all stages. We conclude that the developed framework together with the seven-stage co-benefit assessment process represent a valuable tool for guiding thinking and identifying the multiple values of NBS implementation

Measurement of B(t->Wb)/B(t->Wq) at the Collider Detector at Fermilab

We present a measurement of the ratio of top-quark branching fractions R= B(t -> Wb)/B(t -> Wq), where q can be a b, s or a d quark, using lepton-plus-jets and dilepton data sets with integrated luminosity of ~162 pb^{-1} collected with the Collider Detector at Fermilab during Run II of the Tevatron. The measurement is derived from the relative numbers of t-tbar events with different multiplicity of identified secondary vertices. We set a lower limit of R > 0.61 at 95% confidence level.Comment: 7 pages, 2 figures, published in Physical Review Letters; changes made to be consistent with published versio

Protest Cycles and Political Process: American Peace Movements in the Nuclear Age

Since the dawn of the nuclear age small groups of activists have consistently protested both the content of United States national security policy, and the process by which it is made. Only occasionally, however, has concern about nuclear weapons spread beyond these relatively marginal groups, generated substantial public support, and reached mainstream political institutions. In this paper, I use histories of peace protest and analyses of the inside of these social movements and theoretical work on protest cycles to explain cycles of movement engagement and quiescence in terms of their relation to external political context, or the "structure of political opportunity." I begin with a brief review of the relevant literature on the origins of movements, noting parallels in the study of interest groups. Building on recent literature on political opportunity structure, I suggest a theoretical framework for understanding the lifecycle of a social movement that emphasizes the interaction between activist choices and political context, proposing a six-stage process through which challenging movements develop. Using this theoretical framework I examine the four cases of relatively broad antinuclear weapons mobilization in postwar America. I conclude with a discussion of movement cycles and their relation to political alignment, public policy, and institutional politics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68552/2/10.1177_106591299304600302.pd

Megascopic Quantum Phenomena. A Critical Study of Physical Interpretations

A megascopic revalidation is offered providing responses and resolutions of current inconsistencies and existing contradictions in present-day quantum theory. As the core of this study we present an independent proof of the Goldstone theorem for a quantum field formulation of molecules and solids. Along with phonons two types of new quasiparticles appear: rotons and translons. In full analogy with Lorentz covariance, combining space and time coordinates, a new covariance is necessary, binding together the internal and external degrees of freedom, without explicitly separating the centre-of-mass, which normally applies in both classical and quantum formulations. The generally accepted view regarding the lack of a simple correspondence between the Goldstone modes and broken symmetries, has significant consequences: an ambiguous BCS theory as well as a subsequent Higgs mechanism. The application of the archetype of the classical spontaneous symmetry breaking, i.e. the Mexican hat, as compared to standard quantum relations, i.e. the Jahn-Teller effect, superconductivity or the Higgs mechanism, becomes a disparity. In short, symmetry broken states have a microscopic causal origin, but transitions between them have a teleological component. The different treatments of the problem of the centre of gravity in quantum mechanics and in field theories imply a second type of Bohr complementarity on the many-body level opening the door for megascopic representations of all basic microscopic quantum axioms with further readings for teleonomic megascopic quantum phenomena, which have no microscopic rationale: isomeric transitions, Jahn-Teller effect, chemical reactions, Einstein-de Haas effect, superconductivity-superfluidity, and brittle fracture.Comment: 117 pages, 17 sections, final revised version from 20 May 2019 but uploaded after the DOI was know

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival