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Refereed/Peer-reviewed The paper investigates the pricing strategies of newly-graduated artists and identifies innovative strategies more suited to achieving sustainable practice. Our work is novel in investigating the drivers of discrepancies between artists’ willingness-to-accept (WTA) and potential customers’ willingness-to-pay (WTP). Using mixed-methods, we explore the viewpoints of the ‘public’, by survey, and of ‘newly-graduated artists’ and ‘intermediaries’, by interviews, and interrogate price lists and sales records. Newly-graduated artists find pricing challenging, leading to ‘underpricing’ or ‘over-pricing’. Few artists make sales, reflecting discrepancies between WTA and WTP. Our work has theoretical and practical implications. Pricing reflects the ‘endowment effect’ (Thaler, 1980) and Bourdieu’s ‘avant-garde’ circuit. Our results imply a need for educational institutions and other intermediaries to offer more advice to newly-graduated artists who might benefit from adopting forms of personalized or participative pricing such as ‘Pay What You Want’ and, given the emergence of digital markets, contemporary techniques such as ‘action rules’.

Background:Prenatal diagnosis (preDx) of critical congenital heart disease (CCHD) decreases neonatal morbidity and mortality. Obstetrical fetal cardiac imaging guidelines in 2013 aimed to increase preDx. Objective: To determine the contemporary preDx rate of CCHD and identify maternal-fetal factors and variations in prenatal care that may be potential barriers. Methods: This retrospective single center study evaluated maternal demographics and characteristics of infants with CCHD (requiring cardiac catheterization or surgical intervention before 6 months-old) between 2016 and 2019. Results:58% of the 339 infants with CCHD had preDx. Infants with preDx were more likely to have mothers ≥ 35 years-old (p=0.028), family history of CHD (p=0.017), health insurance (p=0.002), or anatomic scan with perinatology (pConclusion:PreDx rates of CCHD remains inadequate across subtypes detectable by standard fetal cardiac screening views, particularly in uninsured and Hispanic communities.

This article investigates the nature of tensions “on the ground” between the internal and external stakeholders of arts organizations in terms of performance measurement. Based on the qualitative analysis of 19 interviews, the performance measurement practices of two different-sized arts organizations highlight internal and external stakeholders' contrasting perspectives on a number of measurement dimensions. In endeavoring to understand tensions between internal and external stakeholders, the article highlights the main differences which result from seemingly opposed ways of knowing. Internal stakeholders tend more to reflect “phronesis,” based on value-rationality, while external stakeholders are more inclined to technical (“techne”), or analytical (“episteme”) knowledge based on instrumental rationality. Nevertheless, there is some evidence of positive engagement between internal and external stakeholders. The article argues that in order to mitigate tensions, internal and external stakeholders should aim for culturally embedded understanding through evaluation-focused dialogue. In providing both theoretical contributions to nonprofit literature and managerial implications, the article offers an original perspective that challenges existing practice and calls for greater understanding of conflicting interests when different stakeholders are involved in performance measurement. Refereed/Peer-reviewed

The primary purpose of this case study was to develop, implement, and evaluate a new workshop-based intervention using the five-step career planning and reflect on feedback from participants (n = 17) with the aim of improving the intervention’s content and structure to apply it to a wider population of higher education students, including student athletes. The workshop-based intervention aimed to provide participants with opportunities to reflect on career planning and mapping while reviewing their past, present, and future in terms of both sports careers and life, generally. We provide our reflections for both applied researchers and practitioners on our experience of piloting the intervention. Semistructured interview data were collected from the participants. Analysis revealed that the workshop afforded participants with opportunities to reflect on their present and future careers. The participants also provided recommendations on how to improve future workshops. Reflections on these recommendations and on the workshop (development, implementation, and evaluation) are provided.

Studying how assemblages vary across environmental gradients provides a baseline for how assemblages may respond to climate change. Per the biological insurance hypothesis, assemblages with more variation in functional diversity will maintain ecosystem functions when species are lost. In complement, environmental heterogeneity supports landscape-scale ecosystem functionality (i.e. spatial insurance), when that variation includes environments with more abundant resources.We use the relationship between vascular plant functional diversity and microenvironment to identify where assemblages are most likely to maintain functionality in a mountainous fieldsite in northeastern Utah, USA. We assessed how life history strategies and information about phylogenetic differences affect these diversity-environment relationships.We found less functionally dispersed assemblages, that were shorter and more resource-conservative on hotter, more variable, south-facing slopes. In contrast, we found more functionally dispersed assemblages, that were taller and more resource-acquisitive on cooler, less variable, north-facing slopes. Herbaceous and woody perennials drove these trends. Additionally, including information about phylogenetic differences in a dispersion metric indicated that phylogeny accounts for traits we did not measure.Synthesis. At our fieldsite, soil temperature acts as an environmental filter across aspect. If soil temperature increases and becomes more variable, the function of north- vs. south-facing assemblages may be at risk for contrasting reasons. On south-facing slopes, assemblages may not have the variance in functional diversity needed to respond to more intense, stressful conditions. Conversely, assemblages on north-facing slopes may not have the resource-conservative strategies needed to persist if temperatures become hotter and more variable. We suggest that studying dispersal traits, especially of perennial species, will provide additional insight into whether this landscape will maintain function as climate changes.

Aim: COVID-19 resulted in a shortage of personal protective equipment. Community members united to 3D-print face shield headbands to support local healthcare workers. This study examined factors altering print time and strength. Materials & methods: Combinations of infill density (50%, 100%), shell thickness (0.8, 1.2 mm), line width (0.2 mm, 0.4 mm), and layer height (0.1 mm, 0.2 mm) were evaluated through tensile testing, finite element analysis, and printing time. Results: Strength increased with increased infill (p

The COVID-19 pandemic has affected millions of people worldwide. While coronaviruses typically have low rates of neurotropic effects, the massive transmission of SARS-CoV-2 suggests that a substantial population will suffer from potential SARS-CoV-2-related neurological disorders. The rapid and recent emergence of SARS-CoV-2 means little research exists on its potential neurological effects. Here we analyze the effects of similar viruses to provide insight into the potential effects of SARS-CoV-2 on the nervous system and beyond. Seven coronavirus strains (HCoV-OC43, HCoV-HKU1, HCoV-229E, HCoV-NL63, SARS-CoV, MERS-CoV, SARS-CoV-2) can infect humans. Many of these strains cause neurological effects, such as headaches, dizziness, strokes, seizures, and critical illness polyneuropathy/myopathy. Certain studies have also linked coronaviruses with multiple sclerosis and extensive central nervous system injuries. Reviewing these studies provides insight into the anticipated effects for patients with SARS-CoV-2. This review will first describe the effects of other coronaviruses that have caused severe disease (SARS-CoV, MERS-CoV) on the nervous system, as well as their proposed origins, non-neurological effects, and neurological infection mechanisms. It will then discuss what is known about SARS-CoV-2 in these areas with reference to the aforementioned viruses, with the goal of providing a holistic picture of SARS-CoV-2.

The Environmental Kuznets Curve, as a topic widely discussed in academia these days, needs to be further empirically tested. Taking the statistical data of 285 cities from 2003 to 2016 in China as the research sample, this paper uses a dynamic spatial panel model to analyze the impact of economic growth on haze pollution. The conclusions reveal that from an overall perspective, economic growth and haze pollution is always closely related, presenting an inverted U-shaped relationship; that is, the Environmental Kuznets Curve has been verified. Additionally, 26.84% of the sample cities in China have already exceeded the inflection point, meaning that economic growth has gradually led to the effective treatment of haze pollution. This is, however, restricted by stages of urban economic development. To be specific, economic growth has no significant impact on haze pollution when industrialization is in its infancy. Growth, however, exacerbates haze pollution in cities in the middle stages of industrialization although haze pollution does improve for cities in the later stages of industrialization. This means that Chinese cities should formulate reasonable and effective haze pollution control policies and measures according to their own economic development stage.

The East Toronto Health Partners (ETHP) include more than 50 organizations working collaboratively to create an integrated system of care in the east end of Toronto. This existing partnership proved invaluable as a platform for a rapid, coordinated local response to the COVID-19 pandemic. Months after the first wave of the pandemic began, with the daily numbers of COVID-19 cases finally starting to decline, leaders from ETHP provided preliminary reflections on two critical questions: (1) How were existing integration efforts leveraged to mobilize a response during the COVID-19 crisis? and (2) How can the response to the initial wave of COVID-19 be leveraged to further accelerate integration and better address subsequent waves and system improvements once the pandemic abates?

The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction.This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria.1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism.Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD.

Research on best practices for family member involvement has shown that such involvement improves care quality in critical care settings and helps to reduce medical errors leading to adverse events. Although many critical care units promote the principle of "patient-centered care" and family member involvement, there can be a significant gap between knowledge about these processes and their translation into practice. This article is based on an implementation trial of a patient and family involvement knowledge-based tool that involves an educational component for frontline health care workers. By combining ethnographic observation, semistructured interviews, focus groups, and document analysis, we were able to not only examine health care provider views on family involvement but also explore the areas of tension that arose in practice because the introduction of the family involvement tool exposed local factors that shaped the conditions of possibility of family involvement. In particular, unspoken preferences, assumptions, and concerns about family involvement were brought to the fore because this intervention disrupted well-entrenched power dynamics related to family involvement and professional boundaries. Through this ethnographic research, we found that the concept of patient-centered care is not uncontroversial among health care providers and that the form of its practice was largely up for individual interpretation. Interventions and policies that aim to promote patient-centered and family-centered care would benefit from addressing the ways in which these ideas affect the work of different health care professionals and incorporating nursing concerns around family involvement.

The serine hydrolase monoacylglycerol lipase (MAGL) is the rate-limiting enzyme responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. Inhibition of 2-AG degradation leads to elevation of 2-AG, the most abundant endogenous agonist of the cannabinoid receptors (CBs) CB1 and CB2. Activation of these receptors has demonstrated beneficial effects on mood, appetite, pain, and inflammation. Therefore, MAGL inhibitors have the potential to produce therapeutic effects in a vast array of complex human diseases. The present report describes the pharmacologic characterization of [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone (JNJ-42226314), a reversible and highly selective MAGL inhibitor. JNJ-42226314 inhibits MAGL in a competitive mode with respect to the 2-AG substrate. In rodent brain, the compound time- and dose-dependently bound to MAGL, indirectly led to CB1 occupancy by raising 2-AG levels, and raised norepinephrine levels in cortex. In vivo, the compound exhibited antinociceptive efficacy in both the rat complete Freund’s adjuvant–induced radiant heat hypersensitivity and chronic constriction injury–induced cold hypersensitivity models of inflammatory and neuropathic pain, respectively. Though 30 mg/kg induced hippocampal synaptic depression, altered sleep onset, and decreased electroencephalogram gamma power, 3 mg/kg still provided approximately 80% enzyme occupancy, significantly increased 2-AG and norepinephrine levels, and produced neuropathic antinociception without synaptic depression or decreased gamma power. Thus, it is anticipated that the profile exhibited by this compound will allow for precise modulation of 2-AG levels in vivo, supporting potential therapeutic application in several central nervous system disorders. SIGNIFICANCE STATEMENT Potentiation of endocannabinoid signaling activity via inhibition of the serine hydrolase monoacylglycerol lipase (MAGL) is an appealing strategy in the development of treatments for several disorders, including ones related to mood, pain, and inflammation. [1-(4-Fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone is presented in this report to be a novel, potent, selective, and reversible noncovalent MAGL inhibitor that demonstrates dose-dependent enhancement of the major endocannabinoid 2-arachidonoylglycerol as well as efficacy in models of neuropathic and inflammatory pain.

The recent SARS-CoV-2 outbreak has researchers working tirelessly to understand the virus' pathogenesis and develop an effective vaccine. The urgent need for rapid development and deployment of such a vaccine has illustrated the limitations of current practices, and it has highlighted the need for alternative models for early screening of such technologies. Traditional 2D cell culture does not accurately capture the effects of a physiologically relevant environment as they fail to promote appropriate cell-cell and cell-environment interactions. This inability to capture the intricacies of the in vivo microenvironment prevents 2D cell cultures from demonstrating the necessary properties of native tissues required for the standard infection mechanisms of the virus, thus contributing the high failure rate of drug discovery and vaccine development. 3D cell culture models can bridge the gap between conventional cell culture and in vivo models. Methods such as 3D bioprinting, spheroids, organoids, organ-on-chip platform, and rotating wall vessel bioreactors offer ways to produce physiologically relevant models by mimicking in vivo microarchitecture, chemical gradients, cell–cell interactions and cell–environment interactions. The field of viral biology currently uses 3D cell culture models to understand the interactions between viruses and host cells, which is crucial knowledge for vaccine development. In this review, we discuss how 3D cell culture models have been used to investigate disease pathologies for coronaviruses and other viruses such as Zika Virus, Hepatitis, and Influenza, and how they may apply to drug discovery and vaccine development.

We report here the synthesis and characterization of a dual 5-HT

PurposeTo assess feasibility of producing intelligible and comprehensible speech with an electrolarynx; measure anxiety, communication ease, and satisfaction before/after electrolarynx training; and identify barriers/facilitators.MethodsWe included tracheostomized adults from 3 units following commands, reading English, and mouthing words. On enrolment, we measured anxiety, ease, and satisfaction with communication. We gave electrolarynx instruction for ≤5 days then 2 independent raters assessed intelligibility, sentence comprehensibility (9-point difficulty scale), and Electrolarynx Effectiveness Score (EES), and re-evaluated anxiety, communication ease, and satisfaction. Interviews explored barriers/facilitators.Measurements and main resultsWe recruited 24 participants (Jan2015-Dec2016). Mean (SD) intelligibility was 45%(18%) words correct: 57%(21%) when facing. Mean comprehension difficulty was 6.4(2.0) overall, indicating moderate difficulty (5.5(2.5) scored visualizing). Mean EES was 2.9(1.0) (3 = improved lip-reading through recognizable sounds). Anxiety decreased from median 3.8 to 2.0 (P = .007). Communication was rated easier (median 15 vs 12, P = .04) whereas satisfaction remained similar (P = .06). Facilitators included device friendliness, patient independence, and word intelligibility. Barriers were patient weakness, difficulty positioning the device, and limited sentence as opposed to word intelligibility.ConclusionThe electrolarynx may aid intelligible speech for some tracheostomized patients if the communication partner can visualize the users face, and reduce anxiety and make patient perceived communication easier.

Emerging data continues to point towards a relationship between neuroinflammation and neuropsychiatric disorders. ATP-induced activation of P2X7 results in IL-1β release causing neuroinflammation and microglial activation. This study describes the in-vitro and in-vivo neuropharmacology of a novel brain-penetrant P2X7 antagonist, JNJ-55308942, currently in clinical development. JNJ-55308942 is a high-affinity, selective, brain-penetrant (brain/plasma of 1) P2X7 functional antagonist. In human blood and in mouse blood and microglia, JNJ-55308942 attenuated IL-1β release in a potent and concentration-dependent manner. After oral dosing, the compound exhibited both dose and concentration-dependent occupancy of rat brain P2X7 with an ED(50) of 0.07 mg/kg. The P2X7 antagonist (3 mg/kg, oral) blocked Bz-ATP-induced brain IL-1β release in conscious rats, demonstrating functional effects of target engagement in the brain. JNJ-55308942 (30 mg/kg, oral) attenuated LPS-induced microglial activation in mice, assessed at day 2 after a single systemic LPS injection (0.8 mg/kg, i.p.), suggesting a role for P2X7 in microglial activation. In a model of BCG-induced depression, JNJ-55308942 dosed orally (30 mg/kg), reversed the BCG-induced deficits of sucrose preference and social interaction, indicating for the first time a role of P2X7 in the BCG model of depression, probably due to the neuroinflammatory component induced by BCG inoculation. Finally, in a rat model of chronic stress induced sucrose intake deficit, JNJ-55308942 reversed the deficit with concurrent high P2X7 brain occupancy as measured by autoradiography. This body of data demonstrates that JNJ-55308942 is a potent P2X7 antagonist, engages the target in brain, modulates IL-1β release and microglial activation leading to efficacy in two models of anhedonia in rodents.

Rationale: Several studies have explored the experiences of ventilator-assisted individuals living at home with family caregivers. However, few explore the experiences of these individuals as they ...

The synthesis and preclinical characterization of novel 4-(R)-methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridines that are potent and selective brain penetrant P2X7 antagonists are described. Optimization efforts based on previously disclosed unsubstituted 6,7-dihydro-4H-triazolo[4,5-c]pyridines, methyl substituted 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazines, and several other series lead to the identification of a series of 4-(R)-methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridines that are selective P2X7 antagonists with potency at the rodent and human P2X7 ion channels. These novel P2X7 antagonists have suitable physicochemical properties, and several analogs have an excellent pharmacokinetic profile, good partitioning into the CNS and show robust in vivo target engagement after oral dosing. Improvements in metabolic stability led to the identification of JNJ-54175446 (14) as a candidate for clinical development. The drug discovery efforts and strategies that resulted in the identification of the clinical candidate are described herein.

Background∼5–10% of adults may have undiagnosed airflow obstruction. The objective of this study was to develop a population-based case-finding strategy to assess the prevalence of undiagnosed airflow obstruction (asthma or COPD) amongst adults with respiratory symptoms in Canada.MethodsAdults without a previous history of asthma, COPD or lung disease were recruited using random digit-dialling and asked if they had symptoms of dyspnoea, cough, sputum or wheeze within the past 6 months. Those who answered affirmatively completed the Asthma Screening Questionnaire (ASQ), COPD-Diagnostic Questionnaire (COPD-DQ) and COPD Assessment Test (CAT). Those with an ASQ score of ≥6 or a COPD-DQ score of ≥20 underwent pre- and post-bronchodilator spirometry to diagnose asthma or COPD.Results12 117 individuals were contacted at home and assessed for study eligibility. Of the 1260 eligible individuals, 910 (72%) enrolled and underwent spirometry. Ultimately, 184 subjects (20% of those enrolled) had obstructive lung disease (73 asthma and 111 COPD). Individuals found to have undiagnosed asthma or COPD had more severe respiratory symptoms and impaired quality of life compared with those without airflow obstruction. The ASQ, COPD-DQ, and CAT had ROC areas for predicting undiagnosed asthma or COPD of 0.49, 0.64 and 0.56, respectively. Four descriptive variables (age, BMI, sex and pack-years smoked) produced better receiver operating characteristic (ROC) values than the questionnaires (ROC area=0.68).Conclusion20% of randomly selected individuals who report respiratory symptoms in Canada have undiagnosed airflow obstruction due to asthma or COPD. Questionnaires could exclude subjects at low risk but lack the ability to accurately find subjects with undiagnosed disease.

“BEST. PD. EVER!” Some teachers make bold claims for the way that Twitter supports their professional development, yet research into this area is rather limited. This study sought to gain a better understanding of the practices involved and the part that Twitter plays. It uses a sociomaterial sensibility informed by actor-network theory (ANT) to unravel the complex webs of relations which form, break apart and reform when knowledge practices are enacted in the mediated arena of Twitter.\ud To explore this rich but messy environment, I evoke the spirit of the Parisian flâneur to develop an ethnographic approach I refer to as ‘flânography.’ Characterised by purposeful wandering, the approach coupled participant observation and interviews, with emerging methods involving a bot and a 'walkie-talkie' app. Adopting the sensibility of the flâneur consistently through data collection, analysis and presentation resulted in traversals which render pathways of experience. This led to me presenting the findings in three ‘Gatherings’ (Law, 2004a), each taking a tweet or other data snippet as a point of departure. Through the Gatherings I present the activities of both human and nonhuman participants, establish how they came together (or didn’t) and gain a better appreciation of the outcomes of those interrelationships.\ud In reading across the Gatherings, two interlocking dimensions emerged through which teachers' learning practices on Twitter might be conceptualised. ‘Compound learning’ describes how practices can be understood through three meanings of compound: framed chemically (through formation of bonds and associations), financially (like interest which grows cumulatively) and as a mixture (an assortment of actors engaged in activities). The second dimension describes how compound learning can be enacted across three ‘scales:’ acts, activities and practices.\ud By extending previous research, this thesis contributes a richer and deeper understanding of what ‘Twitter Professional Development’ involves, thereby helping to legitimise it within broader professional development discourse. Adding to the current literature on teachers’ professional learning, this thesis reveals how significant personal-isation is in two senses: that teachers can exercise choice in what, when and how they learn; and secondly, the importance of being able to forge socio-professional connections with fellow educators in different ways. The flânographic approach and the new methods which arose within it offer wider contributions for studies exploring activities which range across online and offline spaces, and through time.

OBJECTIVES: To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis. STUDY DESIGN: This study included neonates with gastroschisis within sites in the University of California Fetal Consortium (UCFC). The study’s primary outcome was growth failure at hospital discharge, defined as a weight or length z-score decrease > 0.8 from birth. Regression analysis was performed to assess changes in z-scores over time. RESULTS: Among 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35–37). Length of stay was 32 days (23–60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z-scores at 14 d, 30 d, and discharge were less than birth (p

Purpose The purpose of this paper is to offer a critique of Sen’s utilisation of aspects of Marx’s thought that inform his idea of justice. Marx’s ideas appear in four main areas of discussion: Sen’s positioning of Marx in relation to the other thinkers in his approach to justice; Marx’s fluid notion of identity and its relation to social choice; the problem of going beyond a subjective perspective to consider objective concerns by considering the impact of what Sen calls “objective illusion”; and the issue of just redistribution. Design/methodology/approach The author utilises a Marxian framework of analysis that engages in immanent critique of Sen’s use of Marx in relation to his theory of justice. This is accomplished through textual analysis and by critical assessment of the analytical Marxist tradition that Sen can be seen as using in his own theories with all their inherent weaknesses. Findings Sen’s attempt to use Marx’s ideas to inform his theory of justice founder because: he groups Marx with thinkers that would not accept his desire for the abolition of capitalism and a more just society beyond it. He reduces Marx to the analytical tradition with all its inherent weaknesses. He resorts to a methodological individualist approach of choice that Marx rejects. His search for positional objectivity is undermined by the power of capitalist ideology and ruling class interest. His discussion of just redistribution ignores how Marx’s approach can overcome the arbitrariness that Sen thinks is inevitable when making just decisions. Research limitations/implications Theoretically, the paper suggests that, based on immanent critique and textual analysis, Sen’s use of Marx’s idea of justice is problematic most notably because Sen keeps his analysis within the framework of capitalism that Marx would reject. The implication for further research is the development of Marx’s own arguments on what constitutes a just society. Practical implications Practically, the paper raises questions about the capacity for justice to be achieved within the capitalist system for the reasons discussed in relation to Sen. Social implications Socially, the paper implies that far greater measures to tackle the injustices of the world are necessary than seem to be admitted to by justice theorists such as Sen. Originality/value The author shows that the use of Marx’s theories to inform Sen’s notion of justice, while to be welcomed, lose their efficacious power to expose the full injustice of capitalism and the need for its transcendence.

The productivity of an iron-based Fischer Tropsch (FT) process strongly depends on the synthesis gas conversion. However, iron is known to oxidize significantly at high CO conversion due to the high reactor water partial pressures. In commercial iron-based FT plant this necessitate operation at low single pass conversion, resulting in high separation and recycling cost of the tail gas and the overall economics of the process. Ruthenium has been reported to demonstrate significant stability in the presence of water, hence the employment of FT catalyst promoted with Ru is expected to permit high CO conversion. In this study the stability of an industrial Fe-based FT catalyst impregnated with ruthenium is investigated. The reactions were carried out at industrially relevant conditions in a 1 dm 3 slurry reactor at 250 °C and 20 bar. It was noted that the Fe promoted with Ru was more stable at high CO conversion implying a significant resistance to deactivation in the presence of water. An increase in CO 2 and CH 4 selectivity and a fall in C 5+ selectivity were also noted.

We report here the synthesis and characterization of a dual 5-HT7 / 5-HT2 receptor antagonist 3-(4-Fluoro-phenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (4j). 4j is a high affinity 5-HT7 and 5-HT2A receptor ligand having a pKi = 8.1 at both receptors. It behaves as an antagonist in an in vitro functional assay for 5-HT2A and as an inverse agonist in an in vitro functional assay for 5-HT7. In a validated in vivo model for central 5-HT7 activity in rats, blockade of 5-carboxamidotryptamine (5-CT) induced hypothermia, 4j shows efficacy at low doses (ED50 = 0.05 mg/kg, p.o., 1 h) and maximal efficacy was observed at 0.3 mg/kg p.o. with a corresponding plasma concentration of ~27 ng/ml. In a validated in vivo model for central 5-HT2A activity, blockade of 2,5-dimethoxy-4-iodoamphetamine (DOI) induced head-twitches in mice, 4j shows efficacy at low doses with an ED50 = 0.3 mg/kg p.o. Ex vivo receptor binding studies demonstrate that 4j occupied 5-HT2A receptor binding sites in the frontal cortex of the rat brain with an ED50 in good agreement with the ED50 value for central functional effect mediated by 5-HT2A receptor (ED50 = 0.8 mg/kg, p.o., 1 h).

Objectives Family caregivers of patients requiring prolonged mechanical ventilation may experience physical and psychological morbidity associated with a protracted intensive care unit experience. Our aim was to explore potentially modifiable support needs and care processes of importance to family caregivers of patients requiring prolonged mechanical ventilation and transition from the intensive care unit to a specialised weaning centre. Research methodology/design A longitudinal qualitative descriptive interview study. Data was analysed using directed content analysis. Setting A 6-bed specialised weaning centre in Toronto, Canada. Findings Eighteen family caregivers completed interviews at weaning centre admission (100%), and at two-weeks (40%) and three-months after discharge (22%) contributing 29 interviews. Caregivers were primarily women (61%) and spouses (50%). Caregivers perceived inadequate informational, emotional, training, and appraisal support by health care providers limiting understanding of prolonged ventilation, participation in care and decision-making, and readiness for weaning centre transition. Participants reported long-term physical and psychological health changes including alterations to sleep, energy, nutrition and body weight. Conclusions Deficits in informational, emotional, training, and appraisal support of family caregivers of prolonged mechanical ventilation patients may increase caregiver burden and contribute to poor health outcomes. Strategies for providing support and maintaining family caregiver health-related quality of life are needed.

This second edition of Australian Bird Names is a completely updated checklist of Australian birds and the meanings behind their common and scientific names, which may be useful, useless or downright misleading! For each species, the authors examine the many-and-varied common names and full scientific name, with derivation, translation and a guide to pronunciation. Stories behind the name are included, as well as relevant aspects of biology, conservation and history. Original descriptions, translated by the authors, have been sourced for many species. As well as being a book about names, this is a book about the history of the ever-developing understanding of birds, about the people who contributed to this understanding and, most of all, about the birds themselves. This second edition has been revised to follow current taxonomy and understanding of the relationships between families, genera and species. It contains new taxa, updated text and new vagrants and will be interesting reading for anyone with a love of birds, words or the history of Australian biology and bird-watching.

Dual orexin receptor antagonists have been shown to promote sleep in various species, including humans. Emerging research indicates that selective orexin-2 receptor (OX2R) antagonists may offer specificity and a more adequate sleep profile by preserving normal sleep architecture. Here, we characterized JNJ-42847922 ([5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone), a high-affinity/potent OX2R antagonist. JNJ-42847922 had an approximate 2-log selectivity ratio versus the human orexin-1 receptor. Ex vivo receptor binding studies demonstrated that JNJ-42847922 quickly occupied OX2R binding sites in the rat brain after oral administration and rapidly cleared from the brain. In rats, single oral administration of JNJ-42847922 (3-30 mg/kg) during the light phase dose dependently reduced the latency to non-rapid eye movement (NREM) sleep and prolonged NREM sleep time in the first 2 hours, whereas REM sleep was minimally affected. The reduced sleep onset and increased sleep duration were maintained upon 7-day repeated dosing (30 mg/kg) with JNJ-42847922, then all sleep parameters returned to baseline levels following discontinuation. Although the compound promoted sleep in wild-type mice, it had no effect in OX2R knockout mice, consistent with a specific OX2R-mediated sleep response. JNJ-42847922 did not increase dopamine release in rat nucleus accumbens or produce place preference in mice after subchronic conditioning, indicating that the compound lacks intrinsic motivational properties in contrast to zolpidem. In a single ascending dose study conducted in healthy subjects, JNJ-42847922 increased somnolence and displayed a favorable pharmacokinetic and safety profile for a sedative/hypnotic, thus emerging as a promising candidate for further clinical development for the treatment of insomnia.

The preclinical characterization of novel phenyl(piperazin-1-yl)methanones that are histamine H3 receptor antagonists is described. The compounds described are high affinity histamine H3 antagonists. Optimization of the physical properties of these histamine H3 antagonists led to the discovery of several promising lead compounds, and extensive preclinical profiling aided in the identification of compounds with optimal duration of action for wake promoting activity. This led to the discovery of two development candidates for Phase I and Phase II clinical trials.

In this thesis, I essay a critical and analytical reflection on my time as Assistant Director General responsible for the Indigenous Education and Training Futures Division of Department of Education and Training Qld, Australia, from 2010-2012. In methodological terms the thesis takes the form of a post hoc case study. The significance of the study lies in the fact that this is one of the few academic studies of policy in the domain of Indigenous education that has been undertaken by an insider., My work as an ADG was influenced by many contextual factors. Of these, I have chosen to highlight the demography that was driving policy concerns, the national debates about the direction Indigenous education should take and the international debates that were impacting on thinking around education in Australia. The work is explicitly grounded in a historical context for two specific reasons. We literally live in the past, and yet the past is unknown to us. My argument is that only when the past is known can a strong and alternative present be possible. The thesis also covers methodological questions in some depth. Here, I endeavour to both explicate and justify my choice of Bhaskarian critical realism as an underpinning conceptual framework. The thesis then moves to a consideration of an alternative approach to Indigenous education called the ���Five Pillars���. The pillars of High Expectations (Chapter Five), Recognition and Identity (Chapter Six), Persuasion (Chapter Six), Connectedness (Chapter Seven) and a Service (Job) Guarantee (Chapter Eight) are foundational to emancipatory education for Indigenous students. The original contribution of the thesis consists of the application of critical realist theory to Indigenous policy; the setting of the discussion within a geo-historical framework; the provision of an academic critique of the international and national discourses that impacted on policy formation, and the outlining of 5 pillars of innovation.

Everywhere we go there are birds, and they all have mysteries to be unravelled. These mysteries include the way they look, from bizarre to apparently mundane, why they live where they live, and the things they do, many of which are far too incredible ever to be imagined as fiction. Birds in Their Habitats is a collection of stories and experiences, which introduce fascinating aspects of birdlife, ecology and behaviour. Informed by a wealth of historical and contemporary research, Ian Fraser takes the reader on a journey through four continents: from places as unfamiliar as the Chonos Archipelago of southern Chile and the arid Sahel woodlands of northern Cameroon to those as familiar as a suburban backyard. This is a book of discovery of birds and the places they live. And with humour and personal insight, it is a book about the sometimes strange world of the people who spend a life absorbed in birds.

In A Secular Age Charles Taylor endorses Mikhail Epstein’s notion of ‘minimal religion’ as his preferred orientation to the good for Western secular society. This article examines the basis of Epstein’s ‘minimal religion’ which rests on the psychoanalytic theories of Sigmund Freud and Carl Jung. It is shown that Freud’s theories are incompatible with Taylor’s own thought, and in the case of Jung, Epstein fails to develop the latter’s contribution to our understanding of religion. Moreover, although Taylor endorses Epstein’s work he makes no reference to Jung. To this end, the importance of Jung’s theories in relation to religion are elucidated and offered as a way to forge a dialogue between a nuanced humanist position and the theistic vision offered by Taylor.

A single pot dipolar cycloaddition reaction/Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure–activity relationships of the new compounds are described. Two of these compounds, (S)-(2-fluoro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone (compound 29) and (S)-(3-fluoro-2-(trifluoromethyl)pyridin-4-yl)(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone (compound 35), were found to have robust P2X7 receptor occupancy at low doses in rat with ED50 values of 0.06 and 0.07 mg/kg, respectively. Compound 35 had notable solubility compared to 29 and showed good tolerability in preclinical species. Compound 35 was chosen as a clinical candidate for advancement into phase I clinical trials to assess safety and tolerability in healthy human...

We sought to evaluate the effectiveness of a multi-component, case manager-led exacerbation prevention/management model for reducing emergency department visits. Secondary outcomes included hospitalisation, mortality, health-related quality of life, chronic obstructive pulmonary disease (COPD) severity, COPD self-efficacy, anxiety and depression.Two-centre randomised controlled trial recruiting patients with ≥2 prognostically important COPD-associated comorbidities. We compared our multi-component intervention including individualised care/action plans and telephone consults (12-weekly then 9-monthly) with usual care (both groups). We used zero-inflated Poisson models to examine emergency department visits and hospitalisation; Cox proportional hazard model for mortality.We randomised 470 participants (236 intervention, 234 control). There were no differences in number of emergency department visits or hospital admissions between groups. We detected difference in emergency department visit risk, for those that visited the emergency department, favouring the intervention (RR 0.74, 95% CI 0.63-0.86). Similarly, risk of hospital admission was lower in the intervention group for those requiring hospital admission (RR 0.69, 95% CI 0.54-0.88). Fewer intervention patients died (21

Melancholy, a very dynamic word, has in fact grown more abstract with time to the point where now, many may find it hard to separate from depression or sadness. While melancholy is of course very related to depression, its meaning nowadays can mean anything from somberly introspective to nostalgic. Different from the modern day use of depression to describe the psychological illness, melancholy in both its early days and now is often used to denote a specific personality characteristic of someone, but to see how this came about, it is important to look at the word's earliest beginning in ancient Greek.

For Amartya Sen, Adam Smith’s notion of the impartial spectator is a device that brings “distant voices” into our moral deliberations in order to prevent us from the parochialism that can limit our views on particular issues. Whilst recognising its importance, this article suggests that there are some problems with the way Sen uses this in his The Idea of Justice. Tensions arise around issues relating to his interpretation of Smith, a one-sided and undialectical understanding of the operation of the impartial spectator, an ambivalence in Sen’s approach between essentialism and cultural relativism, the capacity for people to carry out the demands of the impartial spectator and its efficacy in relation to real moral problems such as Smith’s case of infanticide. The conclusion is that in the search for openness, Sen leaves his idea of justice with insufficient grounding to forge a dialogue that can act as a challenge to entrenched beliefs rather than simply accept them in a limbo of fragile co-existence.

Ian McEwan's critically acclaimed novel Atonement has attracted a number of different interpretations across many themes. However, there has been little attention paid to the issue of class in this work. I seek to rectify this lacuna by offering an examination of the novel utilizing the understanding of class developed by E. P. Thompson. Thompson understands class as a historical relationship that is developed over time and is associated with core concepts such as class experience, class consciousness, class struggle, class hegemony, and fetishism. I use these categories to examine the main characters such as Robbie, Cecilia, and Paul Marshall to illuminate and enhance our understanding of the class contradictions present in the novel. This not only demonstrates the richness of Thompson's framework but also the quality of McEwan's own writing on what he sees as the important issue of class.

Background and Purpose An increasing body of evidence suggests that the purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7) in the CNS may play a key role in neuropsychiatry, neurodegeneration and chronic pain. In this study, we characterized JNJ-47965567, a centrally permeable, high-affinity, selective P2X7 antagonist. Experimental Approach We have used a combination of in vitro assays (calcium flux, radioligand binding, electrophysiology, IL-1β release) in both recombinant and native systems. Target engagement of JNJ-47965567 was demonstrated by ex vivo receptor binding autoradiography and in vivo blockade of Bz-ATP induced IL-1β release in the rat brain. Finally, the efficacy of JNJ-47965567 was tested in standard models of depression, mania and neuropathic pain. Key Results JNJ-47965567 is potent high affinity (pKi 7.9 ± 0.07), selective human P2X7 antagonist, with no significant observed speciation. In native systems, the potency of the compound to attenuate IL-1β release was 6.7 ± 0.07 (human blood), 7.5 ± 0.07 (human monocytes) and 7.1 ± 0.1 (rat microglia). JNJ-47965567 exhibited target engagement in rat brain, with a brain EC50 of 78 ± 19 ng·mL−1 (P2X7 receptor autoradiography) and functional block of Bz-ATP induced IL-1β release. JNJ-47965567 (30 mg·kg−1) attenuated amphetamine-induced hyperactivity and exhibited modest, yet significant efficacy in the rat model of neuropathic pain. No efficacy was observed in forced swim test. Conclusion and Implications JNJ-47965567 is centrally permeable, high affinity P2X7 antagonist that can be used to probe the role of central P2X7 in rodent models of CNS pathophysiology.

BACKGROUND: Growing numbers of critically ill patients require prolonged mechanical ventilation and experience difficulty with weaning. Specialized centres may facilitate weaning through focused interprofessional expertise with an emphasis on rehabilitation.OBJECTIVE: To characterize the population of a specialized prolonged-ventilation weaning centre (PWC) in Ontario, and to report weaning, mobility, discharge and survival outcomes.METHODS: Data from consecutively admitted patients were retrospectively extracted from electronic and paper medical records by research staff and verified by the primary investigator.RESULTS: From January 2004 to March 2011, 144 patients were admitted: 115 (80%) required ventilator weaning, and 29 (20%) required tracheostomy weaning or noninvasive ventilation. Intensive care unit length of stay before admission was a median 51 days (interquartile range [IQR] 35 to 86 days). Of the patients admitted for ventilator weaning, 76 of 115 (66% [95% CI 55% to 75%]) achieved a 24 h tracheostomy mask trial in a median of 15 days (IQR eight to 25 days). Weaning success, defined as no further ventilation for seven consecutive days, was achieved by 61 patients (53% [95% CI 44% to 62%]) in a median duration of 62 days (IQR 46 to 95 days) of ventilation, and 14 days (IQR nine to 29 days) after PWC admission. Seventeen patients died during admission. Of the 91 patients discharged from the PWC for one year, 43 (47.3% [95% CI 37.3% to 57.4%]) survived; of the 78 discharged for two years, 27 (34.6% [95% CI 25.0% to 45.7%]) were alive; of the 53 discharged for three years, 19 (35.9% [95% CI 24.3% to 49.3%]) were alive; and seven of 22 (31.8% [95% CI 16.4% to 52.7%]) survived to five years.CONCLUSIONS: Weaning success was moderate despite a prolonged intensive care unit stay before admission, but was comparable with studies reporting weaning outcomes from centres in other countries. Few patients survived to five years.

Orexin-1 receptor antagonists have been shown to block the reinforcing effects of drugs of abuse and food. However, whether blockade of orexin-2 receptor has similar effects has not been determined. We have recently described the in vitro and in vivo effects of JNJ-10397049, a selective and brain penetrant orexin-2 receptor antagonist.The goal of these studies was to evaluate whether systemic administration of JNJ-10397049 blocks the rewarding effects of ethanol and reverses ethanol withdrawal in rodents. As a comparison, SB-408124, a selective orexin-1 receptor antagonist, was also evaluated.Rats were trained to orally self-administer ethanol (8% v/v) or saccharin (0.1% v/v) under a fixed-ratio 3 schedule of reinforcement. A separate group of rats received a liquid diet of ethanol (8% v/v) and withdrawal signs were evaluated 4 h after ethanol discontinuation. In addition, ethanol-induced increases in extracellular dopamine levels in the nucleus accumbens were tested. In separate experiments, the acquisition, expression, and reinstatement of conditioned place preference (CPP) were evaluated in mice.Our results indicate that JNJ-10397049 (1, 3, and 10 mg/kg, sc) dose-dependently reduced ethanol self-administration without changing saccharin self-administration, dopamine levels, or withdrawal signs in rats. Treatment with JNJ-10397049 (10 mg/kg, sc) attenuated the acquisition, expression, and reinstatement of ethanol CPP and ethanol-induced hyperactivity in mice. Surprisingly, SB-408124 (3, 10 and 30 mg/kg, sc) did not have any effect in these procedures.Collectively, these results indicate, for the first time, that blockade of orexin-2 receptors is effective in reducing the reinforcing effects of ethanol.

A few recent studies suggest that brain histamine levels and signaling via H(3) receptors play an important role in modulation of alcohol stimulation and reward in rodents.The present study characterized the effects of a novel, selective, and brain penetrant H(3) receptor antagonist (JNJ-39220675) on the reinforcing effects of alcohol in rats.The effect of JNJ-39220675 on alcohol intake and alcohol relapse-like behavior was evaluated in selectively bred alcohol-preferring (P) rats using the standard two-bottle choice method. The compound was also tested on operant alcohol self administration in non-dependent rats and on alcohol-induced ataxia using the rotarod apparatus. In addition, alcohol-induced dopamine release in the nucleus accumbens was tested in freely moving rats.Subcutaneous administration of the selective H(3) receptor antagonist dose-dependently reduced both alcohol intake and preference in alcohol-preferring rats. JNJ-39220675 also reduced alcohol preference in the same strain of rats following a 3-day alcohol deprivation. The compound significantly and dose-dependently reduced alcohol self-administration without changing saccharin self-administration in alcohol non-dependent rats. Furthermore, the compound did not change the ataxic effects of alcohol, alcohol elimination rate, nor alcohol-induced dopamine release in nucleus accumbens.These results indicate that blockade of H(3) receptor should be considered as a new attractive mechanism for the treatment of alcoholism.

Neuropeptide S (NPS) is known to produce anxiolytic-like effects and facilitate extinction of conditioned fear. Catecholaminergic neurotransmission in the medial prefrontal cortex (mPFC) has been suggested to be crucially involved in these brain functions. In the current study, we investigated the effect of NPS on the release of dopamine and serotonin in the mPFC by in vivo microdialysis in rats. Central administration of NPS dose-dependently enhanced extracellular levels of dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid, with maximal effects lasting up to 120 min. In contrast, no effect on serotonergic neurotransmission was detected. Dopamine release in the mPFC has been previously linked to modulation of anxiety states and fear extinction. The present results may thus provide a physiological and anatomical basis for the reported effects of NPS on these behaviors.

The pre-clinical characterization of novel aryloxypyridine amides that are histamine H(3) receptor antagonists is described. These compounds are high affinity histamine H(3) ligands that penetrate the CNS and occupy the histamine H(3) receptor in rat brain. Several compounds were extensively profiled pre-clinically leading to the identification of two compounds suitable for nomination as development candidates.