Does distributed leadership have a place in destination management organisations? A policy-makers perspective

Within an increasingly networked environment and recent transitions in the landscape of funding for destination management organisations (DMOs) and destinations, pooling knowledge and resources may well be seen as a prerequisite to ensuring the long-term sustainability of reshaped, yet financially constrained DMOs facing severe challenges to deliver value to destinations, visitors and member organisations. Distributed Leadership (DL) is a recent paradigm gaining momentum in destination research as a promising response to these challenges. Building on the scarce literature on DL in a DMO context, this paper provides a policy-makers’ perspective into the place of DL in reshaped DMOs and DMOs undergoing transformation and explores current challenges and opportunities to the enactment and practice of DL. The underpinned investigation used in-depth, semi-structured interviews with policy-makers from VisitEngland following an interview agenda based on the DMO Leadership Cycle. Policy-makers within VisitEngland saw a multitude of opportunities for DMOs with regards to DL, but equally, they emphasised challenges acting as barriers to realising the potential benefits of introducing a DL model to DMOs as a response to uncertainty in the funding landscape

Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release

Proper dialogue between presynaptic neurons and their targets is essential for correct synaptic assembly and function. At central synapses, Wnt proteins function as retrograde signals to regulate axon remodeling and the accumulation of presynaptic proteins. Loss of Wnt7a function leads to defects in the localization of presynaptic markers and in the morphology of the presynaptic axons. We show that loss of function of Dishevelled-1 (Dvl1) mimics and enhances the Wnt7a phenotype in the cerebellum. Although active zones appear normal, electrophysiological recordings in cerebellar slices from Wnt7a/Dvl1 double mutant mice reveal a defect in neurotransmitter release at mossy fiber–granule cell synapses. Deficiency in Dvl1 decreases, whereas exposure to Wnt increases, synaptic vesicle recycling in mossy fibers. Dvl increases the number of Bassoon clusters, and like other components of the Wnt pathway, it localizes to synaptic sites. These findings demonstrate that Wnts signal across the synapse on Dvl-expressing presynaptic terminals to regulate synaptic assembly and suggest a potential novel function for Wnts in neurotransmitter release

A "superstorm": When moral panic and new risk discourses converge in the media

This is an Author's Accepted Manuscript of an article published in Health, Risk and Society, 15(6), 681-698, 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/13698575.2013.851180.There has been a proliferation of risk discourses in recent decades but studies of these have been polarised, drawing either on moral panic or new risk frameworks to analyse journalistic discourses. This article opens the theoretical possibility that the two may co-exist and converge in the same scare. I do this by bringing together more recent developments in moral panic thesis, with new risk theory and the concept of media logic. I then apply this theoretical approach to an empirical analysis of how and with what consequences moral panic and new risk type discourses converged in the editorials of four newspaper campaigns against GM food policy in Britain in the late 1990s. The article analyses 112 editorials published between January 1998 and December 2000, supplemented with news stories where these were needed for contextual clarity. This analysis shows that not only did this novel food generate intense media and public reactions; these developed in the absence of the type of concrete details journalists usually look for in risk stories. Media logic is important in understanding how journalists were able to engage and hence how a major scare could be constructed around convergent moral panic and new risk type discourses. The result was a media ‘superstorm’ of sustained coverage in which both types of discourse converged in highly emotive mutually reinforcing ways that resonated in a highly sensitised context. The consequence was acute anxiety, social volatility and the potential for the disruption of policy and social change

The variability of methane, nitrous oxide and sulfur hexafluoride in Northeast India

High-frequency atmospheric measurements of methane (CH[subscript 4]), nitrous oxide (N[subscript 2]O) and sulfur hexafluoride (SF[subscript 6]) from Darjeeling, India are presented from December 2011 (CH[subscript 4])/March 2012 (N[subscript 2]O and SF[subscript 6]) through February 2013. These measurements were made on a gas chromatograph equipped with a flame ionization detector and electron capture detector, and were calibrated on the Tohoku University, the Scripps Institution of Oceanography (SIO)-98 and SIO-2005 scales for CH[subscript 4], N[subscript 2]O and SF[subscript 6], respectively. The observations show large variability and frequent pollution events in CH[subscript 4] and N[subscript 2]O mole fractions, suggesting significant sources in the regions sampled by Darjeeling throughout the year. By contrast, SF[subscript 6] mole fractions show little variability and only occasional pollution episodes, likely due to weak sources in the region. Simulations using the Numerical Atmospheric dispersion Modelling Environment (NAME) particle dispersion model suggest that many of the enhancements in the three gases result from the transport of pollutants from the densely populated Indo-Gangetic Plains of India to Darjeeling. The meteorology of the region varies considerably throughout the year from Himalayan flows in the winter to the strong south Asian summer monsoon. The model is consistent in simulating a diurnal cycle in CH[subscript 4] and N[subscript 2]O mole fractions that is present during the winter but absent in the summer and suggests that the signals measured at Darjeeling are dominated by large-scale (~100 km) flows rather than local (<10 km) flows.Massachusetts Institute of Technology. Center for Global Change Science (Director's Fund)Massachusetts Institute of Technology. Joint Program on the Science & Policy of Global ChangeMartin Family Society of Fellows for SustainabilityMIT Energy InitiativeMIT International Science and Technology InitiativeUnited States. National Aeronautics and Space Administration (Grant NNX11AF17G)United States. National Oceanic and Atmospheric Administration (Contract RA133R09CN0062

Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor

Background and Purpose Flecainide is a use-dependent blocker of cardiac Na+ channels. Mechanistic analysis of this block showed that the cationic form of flecainide enters the cytosolic vestibule of the open Na+ channel. Flecainide is also effective in the treatment of catecholaminergic polymorphic ventricular tachycardia but, in this condition, its mechanism of action is contentious. We investigated how flecainide derivatives influence Ca2+-release from the sarcoplasmic reticulum through the ryanodine receptor channel (RyR2) and whether this correlates with their effectiveness as blockers of Na+ and/or RyR2 channels. Experimental Approach We compared the ability of fully charged (QX-FL) and neutral (NU-FL) derivatives of flecainide to block individual recombinant human RyR2 channels incorporated into planar phospholipid bilayers, and their effects on the properties of Ca2+ sparks in intact adult rat cardiac myocytes. Key Results Both QX-FL and NU-FL were partial blockers of the non-physiological cytosolic to luminal flux of cations through RyR2 channels but were significantly less effective than flecainide. None of the compounds influenced the physiologically relevant luminal to cytosol cation flux through RyR2 channels. Intracellular flecainide or QX-FL, but not NU-FL, reduced Ca2+ spark frequency. Conclusions and Implications Given its inability to block physiologically relevant cation flux through RyR2 channels, and its lack of efficacy in blocking the cytosolic-to-luminal current, the effect of QX-FL on Ca2+ sparks is likely, by analogy with flecainide, to result from Na+ channel block. Our data reveal important differences in the interaction of flecainide with sites in the cytosolic vestibules of Na+ and RyR2 channels

Multiple impact therapy : evaluation and design for future study

The theoretical underpinnings of Washington County Children\u27s Services Division (CSD) Immediate Conflict-Resolution Family Treatment Program include the systems theory of family therapy with a focus on communication and roles. One of the many approaches to helping families in crisis, it incorporates theories regarding assessment of and intervention in families in crisis. Finally, while it draws upon several different approaches to family therapy, the Washington County program is most closely related to Multiple Impact Therapy (MIT). Thus, a review of relevant literature must address portions of the above enumerated theories that illuminate the thinking behind the Immediate Conflict- Resolution Family Treatment Program. While each of the four components of the literature review (systems theory, family crisis theory, assessment of families in crisis, and Multiple Impact Therapy) represents a topic area of breadth and complexity, the aspects of each topic area which seem most relevant to Washington County\u27s MIT project have been reviewed

Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants

Reproduced with permission from Environmental Health Perspectives."This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants." doi:10.1289/ehp.1002497Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: they are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites.Support for the workshop, from which this article evolved, was provided by the National Institute of Environmental Health Sciences Superfund Research Program (P42-ES04940)

Testing the Prognostic Accuracy of the Updated Pediatric Sepsis Biomarker Risk Model

Background We previously derived and validated a risk model to estimate mortality probability in children with septic shock (PERSEVERE; PEdiatRic SEpsis biomarkEr Risk modEl). PERSEVERE uses five biomarkers and age to estimate mortality probability. After the initial derivation and validation of PERSEVERE, we combined the derivation and validation cohorts (n = 355) and updated PERSEVERE. An important step in the development of updated risk models is to test their accuracy using an independent test cohort. Objective To test the prognostic accuracy of the updated version PERSEVERE in an independent test cohort. Methods Study subjects were recruited from multiple pediatric intensive care units in the United States. Biomarkers were measured in 182 pediatric subjects with septic shock using serum samples obtained during the first 24 hours of presentation. The accuracy of PERSEVERE 28-day mortality risk estimate was tested using diagnostic test statistics, and the net reclassification improvement (NRI) was used to test whether PERSEVERE adds information to a physiology-based scoring system. Results Mortality in the test cohort was 13.2%. Using a risk cut-off of 2.5%, the sensitivity of PERSEVERE for mortality was 83% (95% CI 62–95), specificity was 75% (68–82), positive predictive value was 34% (22–47), and negative predictive value was 97% (91–99). The area under the receiver operating characteristic curve was 0.81 (0.70–0.92). The false positive subjects had a greater degree of organ failure burden and longer intensive care unit length of stay, compared to the true negative subjects. When adding PERSEVERE to a physiology-based scoring system, the net reclassification improvement was 0.91 (0.47–1.35; p<0.001). Conclusions The updated version of PERSEVERE estimates mortality probability reliably in a heterogeneous test cohort of children with septic shock and provides information over and above a physiology-based scoring system

Climate change adaptation through an integrative lens in Aotearoa New Zealand

Climate change is being felt across all human and natural systems in Aotearoa New Zealand and is projected to worsen this decade as impacts compound and cascade through natural system and sectoral dependencies. The effectiveness of adaptation is constrained by how fast greenhouse gas emissions are reduced globally, the pace of change, the frequency and progression of impacts, and the capacity of our natural, societal and political systems to respond. We explore how these systems and sectors interact with existing and projected climate change stressors by categorising climate change impacts (Trends and Events) and consequential thresholds (Thresholds), and by grouping systems and sectors by types (Typologies). This approach has identified commonalities and differences between the typologies which are illustrated with examples. Critical constraints and opportunities for adaptation have been identified to guide sector adaptation decision-making and for ongoing adaptation progress and effectiveness monitoring. Constraints are found across all sectors, and opportunities exist to address them through modelling and projections, monitoring frameworks, decision tools and measures, governance coordination and integration of the Māori worldview of the relationship between humans and nature. However, limits to adaptation exist and will increase over time unless all sectors and all nations urgently reduce their emissions