Please note, due to essential maintenance online transactions will not be possible between 02:30 and 04:00 BST, on Tuesday 17th September 2019 (22:30-00:00 EDT, 17 Sep, 2019). We apologise for any inconvenience.
To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
When presidents take positions on pending Supreme Court cases or criticize the Court's decisions, they are susceptible to being attacked for acting as bullies and violating the norm of judicial independence. Why then do presidents target Supreme Court decisions in their public appeals? In this book, Paul M. Collins, Jr and Matthew Eshbaugh-Soha argue that presidents discuss the Court's decisions to demonstrate their responsiveness to important matters of public policy and to steer the implementation of the Court's decisions. Using data from Washington to Trump, they show that, far from being bullies, presidents discuss cases to promote their re-election, policy goals, and historical legacies, while attempting to affect the impact of Court decisions on the bureaucracy, Congress, the media, and the public.
Recent Anglophone scholarship has successfully shown that Nietzsche's thought makes important contributions to a wide range of contemporary philosophical debates. In so doing, however, scholarship has lost sight of another important feature of Nietzsche's project, namely his desire to challenge the very conception of philosophy that has been used to assess his merits as a philosopher. In other words, contemporary scholarship has overlooked Nietzsche's contributions to metaphilosophy, i.e. debates around the nature, methods, and aims of philosophy. This important new collection of essays brings together an international group of distinguished scholars to explore and discuss these contributions and debates. It will appeal to anyone interested in metaphilosophy, Nietzsche studies, German studies, or intellectual history.
The most celebrated literary figure of nineteenth-century New Orleans was George Washington Cable. From his early work on mixed-race mothers coping with their light-skinned daughters’ abilities to pass back and forth between white and black communities to his discovery and national dissemination via Scribner’s to his masterpiece, The Grandissimes, its hostile reception in Creole New Orleans, and Cable’s consequent departure from the city and then his final reconciliation: Cable’s life stands as the most literary life in the New Orleans of that era. Cable’s engagement with the issue of race presages some of the discourse surrounding the topic today, with his particular attention to institutional racism and the often subtle, even unconscious ways that racism is perpetuated in ordinary, daily life.
Extant research has established an empirical relationship between fatigue and safety-related outcomes. It is not clear if these findings are relevant to Canadian paramedicine. The purpose of this study was to determine if fatigue and shiftwork variables were related to safety outcomes in Canadian paramedics.
A survey was conducted with ten paramedic services in Ontario with a 40.5% response rate (n = 717). Respondents reported levels of fatigue, safety outcomes (injury, safety compromising behaviours, and medical errors/adverse events), work patterns (types of shifts, hours worked weekly) and demographic characteristics. Univariate and logistic regression analyses were used to assess for significant differences.
In this sample, 55% of paramedics reported being fatigued at work. Fatigued paramedics were over twice as likely to report injuries, three times as likely to report safety compromising behaviors, and 1.5 times more likely to report errors/adverse outcomes. When controlling for fatigue, shift length variables did not consistently influence safety outcomes.
These results create preliminary evidence of a relationship between fatigue and safety outcomes in Canadian paramedicine. While more research is needed, these findings point to the influence fatigue has on safety outcomes and provide an indication that fatigue mitigation efforts may be worthwhile.
In recent years, an increasing number of online archival databases of primary sources related to the history of the African diaspora and slavery have become freely and readily accessible for scholarly and public consumption. This proliferation of digital projects and databases presents a number of challenges related to aggregating data geographically according to the movement of people in and out of Africa across time and space. As a requirement to linking data of open-source digital projects, it has become necessary to delimit the entire continent of precolonial Africa during the era of the slave trade into broad regions and sub-regions that can allow the grouping of data effectively and meaningfully.
OBJECTIVES/SPECIFIC AIMS: To complete a needs assessment and action planning process that engaged clinical and translational research network members in identifying needs through survey feedback, characterizing the needs in small group sessions, and developing recommendations for action at the network’s annual scientific meeting. METHODS/STUDY POPULATION: The project included (1) a survey of 357 members across partner institutions from the Great Plains IDeA CTR Network, (2) 6 - 90 minute brainstorming sessions to characterize needs identified through survey assessment, and (3) 6 - 60 minute sessions to develop recommendations for network improvement based on the characterization activity. Approximately 75 members participated in the characterization and recommendation sessions. RESULTS/ANTICIPATED RESULTS: Seven areas of need from the survey were identified based upon the frequency of identification by network members (support to move research across the translational spectrum, database design and management, data access and sharing, data analysis, recruitment and retention of subjects, support for members who have submitted grants but were repeatedly unsuccessful, mentoring). Members indicated which characterization sessions they were interested in attending and based on the enrollment numbers needs related to unsuccessful grant submitters and mentoring were combined as were needs related to database design and data access-sharing. Sessions resulted in 8 inter-related recommendations for network action that included to (1) develop GP-CTR directory/registry of clinicians, researchers, system partners, that can be used to identify people that want to be involved in research partnerships or mentoring, (2) create a GP CTR Navigators Program to will provide support to network members throughout the collaborative research and grant preparation process, (3) identify and disseminate information about assets (funding, databases/registries) that exist amongst network partners that can be leveraged by member, (4) develop a searchable repository of evidence-based interventions for T3/T4 efforts, (5) review GP CTR supported professional development, and technological resource offerings and identify potential gaps, (6) facilitate opportunities for peer support/networking, (7) provide guidance to GP CTR network institutions looking to adopt policies that will support translational research collaboration, and (8) identify potential barriers to GP CTR network engagement (i.e., infrastructure, communication, marketing). DISCUSSION/SIGNIFICANCE OF IMPACT: This process allowed for a wide range of network members to contribute to actionable recommendations for CTR leadership to move into action and improve the scientific network’s ability to conduct clinical and translational research.
OBJECTIVES/SPECIFIC AIMS: Objective: apply checkpoint inhibitors that are specific to the exhaustive markers expressed on tumor CD8+ T-cells ex vivo in order to improve cytokine release and cytotoxic function in comparison to two control groups: (1.) T-cells that receive no antibodies; (2.) T-cells that receive standard inhibition with PD-1 and CTLA-4 antibodies only. Long-term objective: provide personalized medicine in the treatment of HCC by using checkpoint inhibitors that are specific to the receptors expressed by an individual tumor. METHODS/STUDY POPULATION: The study population includes patients undergoing liver transplantation or surgical resection for HCC. Two grams of tumor, two grams of healthy liver tissue at least one centimeter from the tumor margin, and 50 milliliters of blood will be obtained. Solid tissue will be mechanically and enzymatically disrupted and CD8+ T-cells will be isolated from all sites. Using flow cytometry, the expression of surface receptors PD-1, CTLA-4, LAG-3, TIM-3, BTLA, CD244, and CD160 will be categorized in each tissue to identify which receptors are upregulated in the tumor microenvironment. Up to three antibodies specific to the upregulated receptor(s) on the tumor T-cells will be applied per specimen. The experimental arm will receive these antibodies and co-stimulation with CD3/CD28 and will be compared to two controls. One control will receive only CD3/CD28, and the other will receive CD3/CD28 in addition to the standard combination of PD-1 and CTLA-4 inhibitors. From each condition, flow cytometry will be used to assess the mean production of interleukin-2, tumor necrosis factor-α, interferon-γ, granzyme B, and perforin expression as an assessment of T-cell function. RESULTS/ANTICIPATED RESULTS: Preliminary data from the peripheral blood of healthy controls confirms that the developed flow cytometry panels effectively identify the surface receptors and cytokine production of CD8+ T-cells. Two patients have successfully been enrolled in this study. It is predicted that T-cells extracted from the tumor will express more inhibitory receptors than normal liver or peripheral blood and will have increased function after they are targeted with checkpoint inhibitors that are specific to the inhibitory surface receptors they express. DISCUSSION/SIGNIFICANCE OF IMPACT: HCC is the second leading cause of cancer-related death worldwide and therapeutic options are limited for patients who are not surgical candidates. T-cells are a critical component of the anti-tumor response to HCC. However, T-cells can develop an exhausted phenotype characterized by up-regulated inhibitory receptors (PD-1, CTLA-4, LAG-3, TIM-3, CD-244, CD-160, BTLA) and decreased function, allowing for immune escape. Clinical trials using combined checkpoint inhibition with PD-L1 and CTLA-4 antibodies have been considered a breakthrough for patients with advanced HCC, as up to 25% show an objective tumor response. The explanation for the varied susceptibility to checkpoint inhibition remains unknown and is hypothesized to be secondary to inconsistencies in the expression of surface inhibitory receptors. Although inhibitory receptor expression has been shown to be upregulated under conditions of hepatitis and/or HCC, there has been no single study to effectively investigate the expression of all known inhibitors in order to better explore the interplay between them. It will be of great academic interest and clinical purpose to evaluate individual receptor expression and engage the correlating antibodies given the possibility of synergism between receptors and the need for a more profound anti-tumor T-cell response in HCC.
Self-directed speech is considered an important developmental achievement as a self-regulatory mediator of thinking and behavior. Atypical self-directed speech is often implicated in the self-regulatory challenges characteristic of children with neurodevelopmental disorders. A growing body of evidence provides snapshots across age-levels and diagnoses, often presenting conflicting results. This systematic review is undertaken to impose clarity on the nature, extent, and self-regulatory implications of self-directed speech interruption in children with developmental language disorder (DLD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD).
A rigorous search process of relevant databases (i.e., PsychInfo, PubMed, CINAHL, ERIC) uncovered 19 relevant peer-reviewed articles that investigate self-directed speech in children with neurodevelopmental disorders. Consistent across the research, children with DLD, ASD, and ADHD present with differential development and use of self-directed speech.
In its synthesis of findings, this systematic review clearly explicates the differential ontogenesis of self-directed speech in neurodevelopmental disorders and interprets the self-regulatory implications for children with DLD, ASD, and ADHD. Furthermore, the review spotlights important future research directions to better understand the mechanistic relationship between self-directed speech and self-regulation.
This provocative Element is on the 'state of the art' of theories that highlight policymaking complexity. It explains complexity in a way that is simple enough to understand and use. The primary audience is policy scholars seeking a single authoritative guide to studies of 'multi-centric policymaking'. It synthesises this literature to build a research agenda on the following questions:1. How can we best explain the ways in which many policymaking 'centres' interact to produce policy?2. How should we research multi-centric policymaking?3. How can we hold policymakers to account in a multi-centric system?4. How can people engage effectively to influence policy in a multi-centric system?However, by focusing on simple exposition and limiting jargon, Paul Cairney, Tanya Heikkila, Matthew Wood also speak to a far wider audience of practitioners, students, and new researchers seeking a straightforward introduction to policy theory and its practical lessons.
Early intervention in psychosis (EIP) has been developed as an approach to improve the prognosis of people with psychotic disorders and it has been claimed to be a more efficient model of care. However, the evidence is not definitive and doubts have spread regard to the economic outcomes of EIP services amid the usually restricted mental health budget.
We aimed to review the cost-effectiveness evidence of EIP services worldwide.
We systematically reviewed the economic literature about EIP following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement guidelines. Studies were selected according to previously stated criteria and analysed with standardised critical appraisal tools for trial-based economic evaluations and modelling studies.
A total of 16 studies were selected after applying the eligibility criteria. Most of them were economic evaluations alongside clinical trials. The overall evidence was consistent in the cost-effectiveness of EIP compared with standard care for first episode of psychosis and the Clinical High Risk for Psychosis paradigm. Such evidence was replicated among different health systems, but mainly in high-income countries. The methodological quality of such evidence, however, was moderate and heterogeneity was significant across the studies.
There is consistent evidence that the implementation of EIP services might be a cost-effective alternative across different health systems. Such evidence, nevertheless, derives from heterogeneous and sometimes methodologically flawed studies, reducing the certainty of such statement. More efforts must be done to rigorously assess the value of this intervention, before expanding it among systems where mental health budgets are more constrained.
Background: There is an emerging evidence base that mindfulness for psychosis is a safe and effective intervention. However, empirical data on the within-session effects of mindfulness meditation was hitherto lacking. Aims: The aim of the study was to assess the impact of taking part in a mindfulness for psychosis group, using a within-session self-report measure of general stress, and symptom-related distress. Method: Users of a secondary mental health service (n = 34), who experienced enduring psychotic symptoms, took part in an 8-week mindfulness for psychosis group in a community setting. Mindfulness meditations were limited to 10 minutes and included explicit reference to psychotic experience arising during the practice. Participants self-rated general stress, and symptom-related distress, before and after each group session using a visual analogue scale. Results: Average ratings of general stress and symptom-related distress decreased from pre- to post-session for all eight sessions, although not all differences were statistically significant. There was no increase in general stress, or symptom-related distress across any session. Conclusions: There was evidence of positive effects and no evidence of any harmful effects arising from people with psychotic symptoms taking part in a mindfulness for psychosis session.
The Accountability for Reasonableness (A4R) framework addresses the legitimacy of coverage decision processes by defining four conditions for accountable and reasonable processes: Relevance, Publicity, Appeals, Implementation. Cost-per-quality-adjusted life year (QALY) and multicriteria-centered processes may have distinct implications for meeting A4R conditions. The aim of this study was to reflect on how the diverse features of decision-making processes can be aligned with A4R conditions to guide legitimized decision-making. Rare disease and regenerative therapies (RDRTs) pose special decision-making challenges and offer a useful case study.
To support reflection on how different approaches address the A4R conditions, thirty-four features operationalizing each condition were defined and organized into a matrix. Seven experts from six countries explored and discussed these features during a panel (Chatham House Rule) and provided general and RDRT-specific recommendations for each feature. Responses were analyzed to identify converging and diverging recommendations.
Regarding Relevance, panelists highlighted the importance of supporting deliberation, stakeholder participation and grounding coverage decision criteria in the legal framework, goals of sustainable healthcare and population values. Among seventeen criteria, thirteen were recommended by more than half of panelists. Although the cost-effectiveness ratio was deemed sometimes useful, the validity of universal thresholds to inform allocative efficiency was challenged. Regarding Publicity, panelists recommended communicating the values underlying a decision in reference to broader societal objectives, and being transparent about value judgements in selecting evidence. For Appeals, recommendations included clear definition of new evidence and revision rules. For Implementation, one recommendation was to perform external quality reviews of decisions. While RDRTs raise issues that may warrant special consideration, rarity should be considered in interaction with other aspects (e.g. disease severity, age, budget impact).
Improving coverage decision-making towards accountability and reasonableness involves supporting participation and deliberation, enhancing transparency, and more explicit consideration of multiple decision criteria that reflect normative and societal objectives.
A comprehensive analysis of early dinosaur relationships raised the possibility that the group may have originated in Laurasia (Northern Hemisphere), rather than Gondwana (Southern Hemisphere) as often thought. However, that study focused solely on morphology and phylogenetic relationships and did not quantitatively evaluate this issue. Here, we investigate dinosaur origins using a novel Bayesian framework uniting tip-dated phylogenetics with dynamic, time-sliced biogeographic methods, which explicitly account for the age and locality of fossils and the changing interconnections of areas through time due to tectonic and eustatic change. Our analysis finds strong support for a Gondwanan origin of Dinosauria, with 99 % probability for South America (83 % for southern South America). Parsimony analysis gives concordant results. Inclusion of time-sliced biogeographic information affects ancestral state reconstructions (e.g., high connectivity between two regions increases uncertainty over which is the ancestral area) and influences tree topology (disfavouring uniting fossil taxa from localities that were widely separated during the relevant time slice). Our approach directly integrates plate tectonics with phylogenetics and divergence dating, and in doing so reaffirms southern South America as the most likely area for the geographic origin of Dinosauria.
Rising sea levels due to climate change can have severe consequences for coastal populations and ecosystems all around the world. Understanding and projecting sea-level rise is especially important for low-lying countries such as the Netherlands. It is of specific interest for vulnerable ecological and morphodynamic regions, such as the Wadden Sea UNESCO World Heritage region.
Here we provide an overview of sea-level projections for the 21st century for the Wadden Sea region and a condensed review of the scientific data, understanding and uncertainties underpinning the projections. The sea-level projections are formulated in the framework of the geological history of the Wadden Sea region and are based on the regional sea-level projections published in the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5). These IPCC AR5 projections are compared against updates derived from more recent literature and evaluated for the Wadden Sea region. The projections are further put into perspective by including interannual variability based on long-term tide-gauge records from observing stations at Den Helder and Delfzijl.
We consider three climate scenarios, following the Representative Concentration Pathways (RCPs), as defined in IPCC AR5: the RCP2.6 scenario assumes that greenhouse gas (GHG) emissions decline after 2020; the RCP4.5 scenario assumes that GHG emissions peak at 2040 and decline thereafter; and the RCP8.5 scenario represents a continued rise of GHG emissions throughout the 21st century. For RCP8.5, we also evaluate several scenarios from recent literature where the mass loss in Antarctica accelerates at rates exceeding those presented in IPCC AR5.
For the Dutch Wadden Sea, the IPCC AR5-based projected sea-level rise is 0.07±0.06m for the RCP4.5 scenario for the period 2018–30 (uncertainties representing 5–95%), with the RCP2.6 and RCP8.5 scenarios projecting 0.01m less and more, respectively. The projected rates of sea-level change in 2030 range between 2.6mma−1 for the 5th percentile of the RCP2.6 scenario to 9.1mma−1 for the 95th percentile of the RCP8.5 scenario. For the period 2018–50, the differences between the scenarios increase, with projected changes of 0.16±0.12m for RCP2.6, 0.19±0.11m for RCP4.5 and 0.23±0.12m for RCP8.5. The accompanying rates of change range between 2.3 and 12.4mma−1 in 2050. The differences between the scenarios amplify for the 2018–2100 period, with projected total changes of 0.41±0.25m for RCP2.6, 0.52±0.27m for RCP4.5 and 0.76±0.36m for RCP8.5. The projections for the RCP8.5 scenario are larger than the high-end projections presented in the 2008 Delta Commission Report (0.74m for 1990–2100) when the differences in time period are considered. The sea-level change rates range from 2.2 to 18.3mma−1 for the year 2100.
We also assess the effect of accelerated ice mass loss on the sea-level projections under the RCP8.5 scenario, as recent literature suggests that there may be a larger contribution from Antarctica than presented in IPCC AR5 (potentially exceeding 1m in 2100). Changes in episodic extreme events, such as storm surges, and periodic (tidal) contributions on (sub-)daily timescales, have not been included in these sea-level projections. However, the potential impacts of these processes on sea-level change rates have been assessed in the report.
Rather than model Hegel’s account of terrorism on the struggle for recognition and against domination, I maintain that his account is best understood according to Derrida’s notion of autoimmunity. The logic of autoimmunity models terrorism as a symbolic, suicidal act of violence that is created by and directed against the violence of hegemony. It is also continually stimulated by a messianic and nihilistic ideal. This article provides a historical account of Derrida’s elaboration of this concept through his continual dialogue with Hegel. That concept is then applied to Hegel’s account of religious and political terrorism. Ultimately, this analysis supports a reading of Hegel’s Phenomenology in which the confrontation with terrorism as autoimmunity is its lynchpin and which culminates in a moral community that is radically open to the other, to difference, and to the undecidable rather than being closed off and insulated by so-called absolute knowing.
The prevalence and incidence of obesity are high in people with severe mental illness (SMI). In England, around 6000 people with SMI access care from secure mental health units. There is currently no specific guidance on how to reduce the risk of obesity-related morbidity and mortality in this population.
To identify international evidence that addresses the issue of obesity in mental health secure units.
A mixed method review of evidence (published 2000–2015) was carried out to assess obesity prevalence, intervention and policy change, as well as barriers to change.
Evidence from 22 mainly small, non-comparator studies (reported in 21 papers) using a range of methods was reviewed. Dietary, physical activity and cultural interventions being implemented within secure units to address the problem of obesity showed some promising outcomes for physical health and health education. These were facilitated by adequate organisational resources, staff training and motivated staff. Holistic interventions that included a social and/or competitive element were more likely to be taken up. Involving patients in decision-making mediated the tension between facilitating behaviour change and imposing control. Barriers to successful outcomes included patient movement in and out of units, severity of mental health condition and resistance to change by patients and staff.
Despite the promising outcomes reported, further assessment is needed of the feasibility, acceptability and effectiveness of interventions and policies targeting the obesogenic environment, using robust research methods.