Meetings with Costly Participation: An Empirical Investigation

Despite their importance in economic life, meetings with costly participation are little studied. This paper is an empirical analysis of participation at public meetings. We investigate basic and previously unaddressed questions about meetings with costly participation. Who goes? Does attendance vary with observable characteristics? Do meeting attendees represent the interested population? We find that (1), the opinions of participants do not represent the opinions of the entire regulated population, (2) that the opinions of participants are extreme relative to the whole population, (3) that private information does not affect participation decisions in an important way, and (4), that small changes to meeting protocols have the potential to manipulate the sample of participants. These results lay a foundation for the problem of tailoring meeting protocols to achieve particular welfare objectives.

Inference of single-cell phylogenies from lineage tracing data using Cassiopeia.

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia

Recovery from disturbance requires resynchronization of ecosystem nutrient cycles

Nitrogen (N) and phosphorus (P) are tightly cycled in most terrestrial ecosystems, with plant uptake more than 10 times higher than the rate of supply from deposition and weathering. This near-total dependence on recycled nutrients and the stoichiometric constraints on resource use by plants and microbes mean that the two cycles have to be synchronized such that the ratio of N:P in plant uptake, litterfall, and net mineralization are nearly the same. Disturbance can disrupt this synchronization if there is a disproportionate loss of one nutrient relative to the other. We model the resynchronization of N and P cycles following harvest of a northern hardwood forest. In our simulations, nutrient loss in the harvest is small relative to postharvest losses. The low N:P ratio of harvest residue results in a preferential release of P and retention of N. The P release is in excess of plant requirements and P is lost from the active ecosystem cycle through secondary mineral formation and leaching early in succession. Because external P inputs are small, the resynchronization of the N and P cycles later in succession is achieved by a commensurate loss of N. Through succession, the ecosystem undergoes alternating periods of N limitation, then P limitation, and eventually co-limitation as the two cycles resynchronize. However, our simulations indicate that the overall rate and extent of recovery is limited by P unless a mechanism exists either to prevent the P loss early in succession (e.g., P sequestration not stoichiometrically constrained by N) or to increase the P supply to the ecosystem later in succession (e.g., biologically enhanced weathering). Our model provides a heuristic perspective from which to assess the resynchronization among tightly cycled nutrients and the effect of that resynchronization on recovery of ecosystems from disturbance

Selenium hyperaccumulation offers protection from cell disruptor herbivores

<p>Abstract</p> <p>Background</p> <p>Hyperaccumulation, the rare capacity of certain plant species to accumulate toxic trace elements to levels several orders of magnitude higher than other species growing on the same site, is thought to be an elemental defense mechanism against herbivores and pathogens. Previous research has shown that selenium (Se) hyperaccumulation protects plants from a variety of herbivores and pathogens. Selenium hyperaccumulating plants sequester Se in discrete locations in the leaf periphery, making them potentially more susceptible to some herbivore feeding modes than others. In this study we investigate the protective function of Se in the Se hyperaccumulators <it>Stanleya pinnata </it>and <it>Astragalus bisulcatus </it>against two cell disrupting herbivores, the western flower thrips (<it>Frankliniella occidentalis</it>) and the two-spotted spider mite (<it>Tetranychus urticae</it>).</p> <p>Results</p> <p><it>Astragalus bisulcatus </it>and <it>S. pinnata </it>with high Se concentrations (greater than 650 mg Se kg^-1) were less subject to thrips herbivory than plants with low Se levels (less than 150 mg Se kg^-1). Furthermore, in plants containing elevated Se levels, leaves with higher concentrations of Se suffered less herbivory than leaves with less Se. Spider mites also preferred to feed on low-Se <it>A. bisulcatus </it>and <it>S. pinnata </it>plants rather than high-Se plants. Spider mite populations on <it>A. bisulcatus </it>decreased after plants were given a higher concentration of Se. Interestingly, spider mites could colonize <it>A. bisulcatus </it>plants containing up to 200 mg Se kg^-1dry weight, concentrations which are toxic to many other herbivores. Selenium distribution and speciation studies using micro-focused X-ray fluorescence (μXRF) mapping and Se K-edge X-ray absorption spectroscopy revealed that the spider mites accumulated primarily methylselenocysteine, the relatively non-toxic form of Se that is also the predominant form of Se in hyperaccumulators.</p> <p>Conclusions</p> <p>This is the first reported study investigating the protective effect of hyperaccumulated Se against cell-disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops.</p

Understanding the relationship between costs and the modified Rankin Scale: a systematic review, multidisciplinary consensus and recommendations for future studies

Background and purpose: Cost-of-illness studies often describe a single aggregate cost of a disease state. This approach is less helpful for a condition with a spectrum of outcomes like stroke. The modified Rankin Scale is the most commonly used outcome measure for stroke. We sought to describe the existing evidence on the costs of stroke according to individual modified Rankin Scale categories. This may be useful in future cost effectiveness modelling studies of interventions where cost data have not been collected, but disability outcome is known. Methods: Systematic review of the published literature, searching electronic databases between 2004 and 2015 using validated search filters. Results were screened to identify studies presenting costs by individual modified Rankin Scale categories. Results: Of 17,782 unique identified articles, 13 matched all inclusion criteria. In only four of these studies were costs reported by modified Rankin Scale categories. Most studies included direct medical costs only. Societal costs were assessed in two studies. Overall, studies had a high methodological and reporting quality. The heterogeneity in costing methods used in the identified studies prevented meaningful comparison of the reported cost data. Despite this limitation, the costs consistently increased with greater severity (increasing modified Rankin Scale score). Conclusions: Few cost studies of stroke include information based on stroke recovery measured by individual modified Rankin Scale categories and the existing data are limited. To reliably capture this information, future studies are needed that preferably apply standardised costing methods to promote greater potential for use in cost-effectiveness analyses whereby direct collection of patient-level resource use has not been possible

A qualitative study of decision-making and safety in ambulance service transitions

Background Decisions made by front-line ambulance staff are often time critical and based on limited information, but wrong decisions in this context could have serious consequences for patients. There has been little research carried out in the ambulance service setting to identify areas of risk associated with decisions about patient care. Aim The aim of this study was to qualitatively examine potential system-wide influences on decision-making in the ambulance service setting and to identify useful areas for future research and intervention. Methods We used a multisite, multimethod qualitative approach across three ambulance service trusts. In phase 1 we carried out 16 interviews to contextualise the study and provide discussion points for phase 2. For phase 2, university and ambulance service researchers observed paramedics on 34 shifts and 10 paramedics completed ‘digital diaries’ that reported challenges to decision-making or to patient safety. Six focus groups were held, three with staff (n = 21) and three with service users (n = 23). From observation and diary data we developed a typology of decisions made at the scene. Data from these and other sources were also coded within a human factors framework and then thematically analysed to identify influences on those decisions. In phase 3, workshops were held at each site to allow participants and stakeholders (n = 45) to comment on the study findings. Participants were asked to rank influences on decisions using a ‘paired comparison’ method. Results Interviews provided the context for further qualitative exploration. Nine types of decision were identified from observations and digital diaries, ranging from emergency department conveyance and specialist emergency pathways to non-conveyance. A synthesis of findings from the observations, diaries and staff focus groups revealed seven overarching system influences on decision-making and potential risk factors: meeting increasing demand for emergency care; impacts of performance regime and priorities on service delivery; access to appropriate care options; disproportionate risk aversion; education, training and professional development for crews; communication and feedback to crews; and ambulance service resources. Safety culture issues were also identified. Data from the service user focus groups reflected similar issues to those identified from the staff focus groups. Service user concerns included call handling and communication, triage, patient involvement in decisions, balancing demand, resources, access to care, risk aversion, geographical location and vulnerable patients. Group discussions highlighted a lack of awareness by the public of how best to use emergency and urgent care services. Workshop attendees were satisfied that the findings reflected relevant issues. The two issues ranked highest for warranting attention were staff training and development and access to alternative care. Conclusions Multiple qualitative methods allowed a range of perspectives to be accessed and validation of issues across perspectives. Recommendations for future research include exploring effective ways of providing access to alternative care pathways to accident and emergency, assessing public awareness and expectations of ambulance and related services, exploring safe ways of improving telephone triage decisions and assessing the effects of different staff skill levels on patient safety

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3&nbsp;years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6&nbsp;months (median). The median age was 72&nbsp;years, and the baseline median prostate-specific antigen level was 15.0&nbsp;ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7&nbsp;months (95% confidence interval [CI], 28.6-32.2&nbsp;months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7&nbsp;months (95% CI, 39.4-46.2&nbsp;months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

De quelques catéchismes créoles anciens: oublis, pertes, disparitions, réapparitions, découvertes

Il existe, dans le très vaste domaine des études postcoloniales, des territoires contigus ou semblables qui connaissent des phénomènes communs mais aux histoires très différentes, sinon radicalement opposées : tels les catéchismes - en langues romanes - fruit de la colonisation. Plus précisément, à l’histoire des catéchismes issus de la colonisation hispano-américaine, s’oppose l’histoire des catéchismes issus de la colonisation française, de l’Amérique et d’ailleurs. Ces derniers arrivent un siècle et demi environ après les espagnols et se manifestent de tout autre manière ; différents en sont l’époque, la scène et les acteurs : les destinateurs mais surtout les destinataires. Ce travail se propose de retracer l’histoire souvent aventureuse des plus anciens catéchismes des colonies ou ex-colonies françaises de la Caraïbe et de l’Océan Indien ; écrits en créole ou, parfois, en d’autres langues autochtones, ils constituent aussi des témoignages linguistiques absolument précieux. Rédigés généralement sur place, mais non toujours publiés, leur histoire est faite d’oublis, pertes, disparitions, réapparitions et découvertes. - - - In the wide field of postcolonial studies, there exist related or similar areas whose stories are nevertheless very different, if not indeed opposed. This is the case of catechisms in Romance languages (or of Romance origin), outcomes of European colonization. In particular, contradictions between the history of catechisms from Hispanic-American colonization and the catechisms produced by French colonization, in America and elsewhere. The latter appear a century and a half after the Spanish texts, and exhibit completely distinct characteristics: different periods, settings, actors, and especially recipients. I set out to recount the often adventurous history of the oldest catechisms in the French colonies, or ex-colonies, of the Caribbean and the Indian Ocean. Written in Creole or sometimes other indigenous languages, they are precious linguistic records. Compiled in the colonies, but not always published, these texts are often forgotten, lost, misplaced, resurfaced, discovered

Xanthine oxidase inhibition for the improvement of long-term outcomes following ischaemic stroke and transient ischaemic attack (XILO-FIST) - Protocol for a randomised double blind placebo-controlled clinical trial

Background: Allopurinol, a xanthine oxidase inhibitor, reduced progression of carotid-intima media thickness and lowered blood pressure in a small clinical trial in people with ischaemic stroke. Xanthine oxidase inhibition for improvement of long-term outcomes following ischaemic stroke and transient ischaemic attack (XILO-FIST) aims to assess the effect of allopurinol treatment on white matter hyperintensity progression and blood pressure after stroke. This paper describes the XILO-FIST protocol. Methods: XILO-FIST is a multicentre randomised double-blind, placebo-controlled, parallel group clinical trial funded by the British Heart Foundation and the Stroke Association. The trial has been adopted by the Scottish Stroke Research Network and the UK Clinical Research Network. The trial is registered in clinicaltrials.gov (registration number NCT02122718). XILO-FIST will randomise 464 participants, aged greater than 50 years, with ischaemic stroke within the past month, on a 1:1 basis, to two years treatment with allopurinol 300 mg twice daily or placebo. Participants will undergo brain magnetic resonance imaging, cognitive assessment, ambulatory blood pressure monitoring and blood sampling at baseline and after two years treatment. The primary outcome will be white matter hyperintensity progression, measured using the Rotterdam progression scale. Secondary outcomes will include change in white matter hyperintensity volume, mean day-time systolic blood pressure and measures of cognitive function. Up to 100 will undergo additional cardiac magnetic resonance imaging in a sub-study of left ventricular mass. Discussion: If white matter hyperintensity progression is reduced, allopurinol could be an effective preventative treatment for patients with ischaemic stroke and clinical endpoint studies would be needed. If allopurinol reduces blood pressure after stroke, then it could be used to help patients reach blood pressure targets