Long-Term Effectiveness of Anti-IL-4R Therapy Following Suboptimal Response to Anti-IL-5/5R Therapy in Severe Eosinophilic Asthma.

BACKGROUND: Dupilumab is an anti-IL-4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL-5/5R mAbs is seen in some patients with ongoing evidence of type 2 (T2) inflammation. OBJECTIVE: To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes. METHODS: We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL-5/5R biologics. The ability to achieve clinical remission and the change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (forced expiratory volume in 1 second), and asthma control (Asthma Control Questionnaire 6) were recorded. RESULTS: Thirty-seven patients (mean age 41 years, 70% female) were included in the analysis. The mean (standard deviation) AER fell by almost 90% from 3.16 (1.28) at dupilumab initiation to 0.35 (0.72) after 1 year. The median (interquartile range) mOCS dose (n = 20) fell from 10 (5-25) mg to 0 (0-5) mg at 1 year, with 14 of 20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16 of 37 (43%). Patients who achieved remission had a higher pre-IL-5/5R fractional exhaled nitric oxide (FeNO) level (85 [39-198] parts per billion [ppb] vs 75 [42-96] ppb, P = .03). CONCLUSIONS: Significant improvements in clinical outcomes are possible after a switch to dupilumab in patients experiencing a suboptimal response to anti-IL-5/5R therapies. A higher FeNO in poor responders to anti-IL-5/5R who achieve remission with dupilumab is suggestive of an IL-13-driven subphenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.

The importance of direct and indirect trophic interactions in determining the presence of a locally rare day-flying moth.

Ecosystem engineers affect other organisms by creating, maintaining or modifying habitats, potentially supporting species of conservation concern. However, it is important to consider these interactions alongside non-engineering trophic pathways. We investigated the relative importance of trophic and non-trophic effects of an ecosystem engineer, red deer, on a locally rare moth, the transparent burnet (Zygaena purpuralis). This species requires specific microhabitat conditions, including the foodplant, thyme, and bare soil for egg-laying. The relative importance of grazing (i.e., trophic effect of modifying microhabitat) and trampling (i.e., non-trophic effect of exposing bare soil) by red deer on transparent burnet abundance is unknown. We tested for these effects using a novel method of placing pheromone-baited funnel traps in the field. Imago abundance throughout the flight season was related to plant composition, diversity and structure at various scales around each trap. Indirect effects of red deer activity were accounted for by testing red deer pellet and trail presence against imago abundance. Imago abundance was positively associated with thyme and plant diversity, whilst negatively associated with velvet grass and heather species cover. The presence of red deer pellets and trails were positively associated with imago abundance. The use of these sites by red deer aids the transparent burnet population via appropriate levels of grazing and the provision of a key habitat condition, bare soil, in the form of deer trails. This study shows that understanding how both trophic and non-trophic interactions affect the abundance of a species provides valuable insights regarding conservation objectives.

The role of risk perception and affect in predicting support for conservation policy under rapid ecosystem change.

Conservation conflicts are damaging for humans and wildlife, with differences in people's objectives fuelling challenges of managing complex, dynamic systems. We investigate the relative importance of economic, psychological (affect, trust and risk perception) and ecological factors in determining farmers' management preferences, using Greenland barnacle geese (Branta leucopsis) on Islay, Scotland, as a case study. Barnacle geese reduce agricultural productivity on Islay, negatively impacting household economies. Since 1992, farmers have received partial compensation but a new culling scheme has escalated conflict between conservation and agricultural interests. Using a questionnaire, we collected data from 75% of the farmers receiving goose payments. We found that affect was a strong driver of both risk perception and management preferences. However, we revealed complexity in these relationships, with trust and economic factors also influencing decision-making. Psychological and economic factors surrounding wildlife management must be understood if we are to achieve conservation objectives in human dominated landscapes.

The influence of different aspects of grouse moorland management on nontarget bird assemblages.

Conflict between stakeholders with opposing interests can hamper biodiversity conservation. When conflicts become entrenched, evidence from applied ecology can reveal new ways forward for their management. In particular, where disagreement exists over the efficacy or ethics of management actions, research clarifying the uncertain impacts of management on wildlife can move debates forwards to conciliation.Here, we explore a case-study of entrenched conflict where uncertainty exists over the impacts of multiple management actions: namely, moorlands managed for the shooting of red grouse (willow ptarmigan) Lagopus lagopus in the United Kingdom (UK). Debate over how UK moorlands should be managed is increasingly polarized. We evaluate, for the first time at a regional scale, the relative impacts of two major moorland management practices-predator control and heather burning-on nontarget bird species of conservation concern.Birds were surveyed on 18 estates across Northern England and Southeast Scotland. Sites ranged from intensively managed grouse moors to moorland sites with no management for grouse shooting. We hypothesised that both targeted predator control and burning regimes would enhance ground-nesting wader numbers and, as a consequence of this, and of increased grouse numbers, nontarget avian predators should also be more abundant on heavily managed sites.There were positive associations between predator control and the abundance of the three most widespread species of ground-nesting wader: strong effects for European golden plover Pluvialis apricaria and Eurasian curlew Numenius arquata and, less strongly, for common snipe Gallinago gallinago. These effects saturated at low levels of predator control. Evidence for effects of burning was much weaker. We found no evidence of enhanced numbers of nontarget predators on heavily managed sites.

Time series analysis reveals synchrony and asynchrony between conflict management effort and increasing large grazing bird populations in northern Europe.

The management of conflicts between wildlife conservation and agricultural practices often involves the implementation of strategies aimed at reducing the cost of wildlife impacts on crops. Vital to the success of these strategies is the perception that changes in management efforts are synchronized relative to changes in impact levels, yet this expectation is never evaluated. We assess the level of synchrony between time series of population counts and management effort in the context of conflicts between agriculture and five populations of large grazing birds in northern Europe. We reveal inconsistent patterns of synchrony and asynchrony between changes in population counts and impact management effort relating to population harvesting, monetary payments, or scaring practices. This variation is likely due to differing management aims, the existence of lags between management decisions and population monitoring, and the inconsistent use of predictive models across case studies. Overall, our findings highlight the need for more adaptive and timely responses of management to changes in target species numbers so as not to unexpectedly increase social conflicts and jeopardize the status of wildlife populations.

Wicked conflict: Using wicked problem thinking for holistic management of conservation conflict.

Conservation conflict is widespread, damaging, and has proved difficult to manage using conventional conservation approaches. Conflicts are often "wicked problems," lacking clear solutions due to divergent values of stakeholders, and being embedded within wickedly complex environments. Drawing on the concept of wicked environmental problems could lead to management strategies better suited to tackling conflict. However, it is unclear whether managers are embracing ideas from the wicked problems concept. There is currently a lack of guidance for applying strategies to tackle particular wicked problems, such as conservation conflict. We explored the suitability of wicked problems-inspired management, using eight contemporary conflict case studies. Conservation conflict was managed predominantly using conventional approaches suited to tackling single objectives in simple environments, rather than balancing competing objectives in complex environments. To deal with different characteristics of wickedness, we recommend that managers develop strategies combining distributed decision-making, diverse opinions, pattern-based predictions, trade-off-based objectives, and reporting of failures. Recent advances in conservation conflict research have focused on improving interactions among stakeholders. We believe that such stakeholder-focused approaches would dovetail with the whole-system focus of a wicked problems framework, allowing conservationists to move toward a holistic strategy for managing conservation conflict.

Functional responses in animal movement explain spatial heterogeneity in animal-habitat relationships.

Understanding why heterogeneity exists in animal-habitat spatial relationships is critical for identifying the drivers of animal distributions. Functional responses in habitat selection - whereby animals adjust their habitat selection depending on habitat availability - are useful for describing animal-habitat spatial heterogeneity. However, they could be yielded by different movement tactics, involving contrasting interspecific interactions. Identifying functional responses in animal movement, rather than in emergent spatial patterns like habitat selection, could disentangle the effects of different movement behaviours on spatial heterogeneity in animal-habitat relationships. This would clarify how functional responses in habitat selection emerge and provide a general tool for understanding the mechanistic drivers of animal distributions. We tested this approach using data from GPS-collared woodland caribou (Rangifer tarandus), a prey species under top-down control. We tested how caribou selected and moved with respect to a key resource (lichen-conifer stands) as a function of the availability of surrounding refuge land-cover (closed-conifer stands), using step selection functions. Caribou selected resource patches more strongly in areas richer in refuge land-cover - a functional response in habitat selection. However, adjustments in multiple movement behaviours could have generated this pattern: stronger directed movement towards resource patches and/or longer residency within resource patches, in areas richer in refuges. Different contributions of these behaviours would produce contrasting forager spatial dynamics. We identified functional responses in both movement behaviours: caribou were more likely to move towards resource patches in areas richer in refuge land-cover, and to remain in these patches during movement steps. This tactic enables caribou to forage for longer in safer areas where they can rapidly seek refuge in dense cover when predators are detected. Our study shows that functional responses in movement can expose the context-dependent movement decisions that generate heterogeneity in animal-habitat spatial relationships. We used these functional responses to characterise anti-predator movement tactics employed by a large herbivore, but they could be applied in many different scenarios. The movement rules from functional responses in movement are well-suited to integration in spatial explicit individual-based models for forecasting animal distributions in landscapes undergoing environmental change.

Novel method to collect medication adverse events in juvenile arthritis: results from the childhood arthritis and rheumatology research alliance enhanced drug safety surveillance project.

OBJECTIVE: Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product-based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4-year (2008-2012) EDSSP. METHODS: Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6-month period. Reporting rates were calculated per 100 person-years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution. RESULTS: Thirty-seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person-years (95% CI 0.95-1.19). The rates for SAEs and IMEs were 0.54 per 100 person-years (95% CI 0.45-0.63) and 0.53 per 100 person-years (95% CI 0.49-0.62), respectively. CONCLUSION: The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product-based registry.

Nutrition and health in amphibian husbandry.

Amphibian biology is intricate, and there are many inter-related factors that need to be understood before establishing successful Conservation Breeding Programs (CBPs). Nutritional needs of amphibians are highly integrated with disease and their husbandry needs, and the diversity of developmental stages, natural habitats, and feeding strategies result in many different recommendations for proper care and feeding. This review identifies several areas where there is substantial room for improvement in maintaining healthy ex situ amphibian populations specifically in the areas of obtaining and utilizing natural history data for both amphibians and their dietary items, achieving more appropriate environmental parameters, understanding stress and hormone production, and promoting better physical and population health. Using a scientific or research framework to answer questions about disease, nutrition, husbandry, genetics, and endocrinology of ex situ amphibians will improve specialists' understanding of the needs of these species. In general, there is a lack of baseline data and comparative information for most basic aspects of amphibian biology as well as standardized laboratory approaches. Instituting a formalized research approach in multiple scientific disciplines will be beneficial not only to the management of current ex situ populations, but also in moving forward with future conservation and reintroduction projects. This overview of gaps in knowledge concerning ex situ amphibian care should serve as a foundation for much needed future research in these areas.

Predicting potential responses to future climate in an alpine ungulate: interspecific interactions exceed climate effects.

The altitudinal shifts of many montane populations are lagging behind climate change. Understanding habitual, daily behavioural rhythms, and their climatic and environmental influences, could shed light on the constraints on long-term upslope range-shifts. In addition, behavioural rhythms can be affected by interspecific interactions, which can ameliorate or exacerbate climate-driven effects on ecology. Here, we investigate the relative influences of ambient temperature and an interaction with domestic sheep (Ovis aries) on the altitude use and activity budgets of a mountain ungulate, the Alpine chamois (Rupicapra rupicapra). Chamois moved upslope when it was hotter but this effect was modest compared to that of the presence of sheep, to which they reacted by moving 89-103 m upslope, into an entirely novel altitudinal range. Across the European Alps, a range-shift of this magnitude corresponds to a 46% decrease in the availability of suitable foraging habitat. This highlights the importance of understanding how factors such as competition and disturbance shape a given species' realised niche when predicting potential future responses to change. Furthermore, it exposes the potential for manipulations of species interactions to ameliorate the impacts of climate change, in this case by the careful management of livestock. Such manipulations could be particularly appropriate for species where competition or disturbance already strongly restricts their available niche. Our results also reveal the potential role of behavioural flexibility in responses to climate change. Chamois reduced their activity when it was warmer, which could explain their modest altitudinal migrations. Considering this behavioural flexibility, our model predicts a small 15-30 m upslope shift by 2100 in response to climate change, less than 4% of the altitudinal shift that would be predicted using a traditional species distribution model-type approach (SDM), which assumes that species' behaviour remains unchanged as climate changes. Behavioural modifications could strongly affect how species respond to a changing climate.

Intraseasonal variation in reproductive effort: young males finish last.

Age-dependent reproductive timing has been observed in females of a number of species; older females often breed earlier in the season and experience higher reproductive success as a result. However, to date, evidence for within-season variation in reproductive effort (RE) for males has been relatively weak. Males are expected to time RE in light of intraseasonal variations in the availability of receptive females and competition with other males. Young males, which are typically smaller and less experienced, might benefit from breeding later in the season, when male-male competition is less intense. Using a long-term data set of Alpine chamois Rupicapra rupicapra, we sought to evaluate the hypothesis that younger males allocate highest RE late in the breeding season, at a time when older male RE has decreased substantially. Our results support this hypothesis, which suggests that intraseasonal variation in RE may be an adaptive life-history trait for males as well as females.

Forensic and non-forensic psychiatric nursing skills and competencies for psychopathic and personality disordered patients.

AIM AND OBJECTIVE: To understand better the skills and competencies for forensic and non-forensic nursing of psychopathic and personality disordered patients. BACKGROUND: In the UK, there has been growing interest in service provision for this client group, but with little research to support the nursing skills required. DESIGN: A non-experimental design, using a postal survey to 990 forensic and 500 non-forensic nurses. METHOD: An information gathering schedule was used to generate data about the most desirable skills and competencies and least desirable weaknesses and nursing attributes to nurse this group. RESULTS: The results for the forensic nurses. Main strengths and skills: being firm, setting limits and defining boundaries. Main weaknesses: inability to engage, inability to resolve conflict and impatience. Main skills and competencies: being non-threatening, non-judgemental and able to expect anything. Least desirable qualities: over-reacting, being judgemental and over-confrontational. The results for the non-forensic nurses. Main strengths and skills: being non-judgemental, listening skills and good risk assessment. Main weaknesses: frustration with the system, a fear of aggression and no skills to engage. Main skills and competencies: being open-minded, non-judgemental and forming relationships. Least desirable qualities: a supercilious attitude, cynicism and being judgemental. CONCLUSION: The results highlight the importance of forming therapeutic relationships as the bedrock of both forensic and non-forensic nursing, and they also highlight the important differences with regard to the significance of therapeutic action and therapeutic verbal interaction. RELEVANCE TO CLINICAL PRACTICE: The provision of better care for this client group will rely on appropriate training for nurses. This research highlights the need for training that supports the development of engagement skills, communication skills and an ability to use reflection in action as a means of providing therapeutic care. It also highlights the different emphasis on the use of these skills by forensic and non-forensic nurses.

Contrasting life histories in neighbouring populations of a large mammal.

BACKGROUND: A fundamental life history question is how individuals should allocate resources to reproduction optimally over time (reproductive allocation). The reproductive restraint hypothesis predicts that reproductive effort (RE; the allocation of resources to current reproduction) should peak at prime-age, whilst the terminal investment hypothesis predicts that individuals should continue to invest more resources in reproduction throughout life, owing to an ever-decreasing residual reproductive value. There is evidence supporting both hypotheses in the scientific literature. METHODOLOGY/PRINCIPAL FINDINGS: We used an uncommonly large, 38 year dataset on Alpine chamois (Rupicapra rupicapra) shot at various times during the rutting period to test these two hypotheses. We assumed that body mass loss in rutting males was strongly related to RE and, using a process-based approach, modelled how male relative mass loss rates varied with age. For different regions of our study area, we provide evidence consistent with different hypotheses for reproductive allocation. In sites where RE declined in older age, this appears to be strongly linked to declining body condition in old males. In this species, terminal investment may only occur in areas with lower rates of body mass senescence. CONCLUSIONS/SIGNIFICANCE: Our results show that patterns of reproductive allocation may be more plastic than previously thought. It appears that there is a continuum from downturns in RE at old age to terminal investment that can be manifest, even across adjacent populations. Our work identifies uncertainty in the relationship between reproductive restraint and a lack of competitive ability in older life (driven by body mass senescence); both could explain a decline in RE in old age and may be hard to disentangle in empirical data. We discuss a number of environmental and anthropogenic factors which could influence reproductive life histories, underlining that life history patterns should not be generalised across different populations.

Violence and under-reporting: learning disability nursing and the impact of environment, experience and banding.

AIMS AND OBJECTIVES: The study explores the implications of a survey into the discrepancy between actual and reported incidents of violence, perpetrated by service users, within the learning disability division of one mental health NHS Trust. BACKGROUND: Violence within the NHS continues to constitute a significant issue, especially within mental health and learning disability services where incidence remains disproportionately high despite the context of zero tolerance. DESIGN: A whole-population survey of 411 nurses working within a variety of settings within the learning disability division of one mental health NHS Trust. METHODS: A questionnaire was administered to learning disability nursing staff working in community, respite, residential, assessment and treatment and medium secure settings, yielding a response rate of approximately 40%. CONCLUSIONS: There were distinct differences in the levels of violence reported within specific specialist services along with variation between these areas according to clinical environment, years of experience and nursing band. The study does not support previous findings whereby unqualified nurses experienced more incidents of violence than qualified nurses. The situation was less clear, complicated by the interrelationship between years of nursing experience, nursing band and clinical environment. The conclusions suggest that the increased emphasis on reducing violent incidents has been fairly successful with staff reporting adequate preparation for responding to specific incidents and being well supported by colleagues, managers and the organisation. The differences between specific clinical environments, however, constituted a worrying finding with implications for skill mix and staff education. RELEVANCE TO CLINICAL PRACTICE: The study raises questions about the relationship between the qualified nurse and the individual with a learning disability in the context of violence and according to specific circumstances of care delivery. The relationship is clearly not a simple one, and this group of nurses' understanding and expectations of tolerance requires further research; violence is clearly never acceptable, but these nurses appear reluctant to condemn and attribute culpability.

Postnatal disclosure of domestic violence: comparison with disclosure in the first trimester of pregnancy.

AIMS AND OBJECTIVES: This study explored the prevalence rates of domestic violence reported during the first trimester of pregnancy and in the postnatal period. BACKGROUND: Domestic violence is known to have a deleterious effect on the physical and psychological well-being of a woman, with an adverse effect on the unborn child. DESIGN: A validated anonymous and self-administered questionnaire (Abuse Assessment Screen) using five closed questions was used for data collection in all samples. All women were approached alone, and the questionnaire was completed in private. METHOD: Drawn from the same geographical area, this survey collected data from women accessing hospital clinics, in a large university teaching hospital in the UK. RESULTS: Comparing self-reporting rates of domestic violence in the first trimester of pregnancy to the postnatal period yielded statistically significant results (p < 0·01). Only 7·3% booking-in clinic and 8% postnatal women reported violence at some stage in their life, whilst higher rates in pregnancy counselling clinic (35·1%) and early pregnancy unit (26%) were reported. However, the reported rates of domestic violence in the year before the women were pregnant revealed a different trajectory. Lower rates of domestic violence were evident in three samples. CONCLUSIONS: The disparity in disclosure rates of domestic violence suggests that an emotional inhibitory response to disclosure may occur at specific periods of pregnancy and that the timing of asking about domestic violence may be critical to this disclosure. The pandemic nature of domestic violence reflects the need for practice in maternity care to reflect the changing needs of a woman during her gestational experience. RELEVANCE TO CLINICAL PRACTICE: The primary objective of health care providers should be to engage a pregnant woman in a meaningful relationship, gaining her trust to facilitate the disclosure of domestic violence. Hence, whatever the policies for the provision of maternity care, the changing needs of a pregnant woman must be met.

Forensic learning disability nursing skills and competencies: a study of forensic and non-forensic nurses.

This paper reports on an investigation into the skills and competencies of forensic learning disability nurses in the United Kingdom. The two sample populations were forensic learning disability nurses from the high, medium, and low secure psychiatric services and non-forensic learning disability nurses from generic services. An information gathering schedule was used to collect the data; of 1200 schedules, 643 were returned for a response rate of 53.5%. The data identified the "top ten" problems that forensic learning disability nurses may encounter, the skills and competencies necessary to overcome them, and the areas that need to be developed in the future. The results indicated that the forensic learning disability nurses tended to focus on the physical aspects to the role whilst the non-forensic learning disability nurses tended to perceive the forensic role in relational terms. This has implications for practice, policy, and procedures.

Is your property tax-exempt status at risk?

Healthcare reform includes specific requirements for hospitals and health systems related to property tax exemption. Some states impose their own requirements for hospitals to qualify as a charity. Hospitals should proactively address property tax exemption status.

Perceptions of diagnostic labels in forensic psychiatric practice: a survey of differences between nurses and other disciplines.

This paper reports on a study of nurses' and non-nurses' perceptions of labels of mental illness and personality disorder in forensic services in the UK. The objectives of the study were to establish if differences in perceptions existed within, and between, the two groups of professionals. The research method was a survey design with 1,200 questionnaires distributed to nurses and 300 to other professionals in disciplines on forensic units in the UK, with response rates of 34.6% and 43%, respectively. The target population included clinical health care staff who had patient contact, including nurses, psychiatrists, psychologists, social workers, and occupational therapists. The results indicate that there are statistically significant differences within both nursing and non-nursing groups and also between the groups in relation to a "management" perspective for individuals labelled with a personality disorder and a "clinical" focus for individuals who are labelled as mentally ill. This paper adds research into the arena of forensic mental health in relation to the diagnostic labels of mental illness and personality disorders. It also adds evidence of a clinical response or a management response to such diagnostic labels which may impact on the practice of forensic psychiatry.

Binary construct analysis of forensic psychiatric nursing in the UK: high, medium, and low security services.

The aim of this study was to identify if differences in perceptions of the role of forensic psychiatric nurses exist across the three levels of secure psychiatric provision: high, medium, and low. Any differences may reflect the type of clinical conditions found in different levels of security provision. An information-gathering schedule containing a validated 7-point Likert scale was distributed to 1200 forensic psychiatric nurses across the UK in 2005. A response rate of 34.6 was achieved, with 122 from high-security, 159 from medium-security, and 135 from low-security services. Differences in perceptions regarding role constructs were found across all three levels, with numerous differences being statistically significant using analysis of variance. The main implications are in relation to the development of skills and competencies, which should target specific clinical conditions in relation to effective interventions, the development of a specialist education and training curriculum focused on treatment outcomes, and the need for further research to draw together theory and practice. Finally, creative policy initiatives should be developed to cross-fertilize the levels of security provision in order that staff may acquire and deliver experiences in high-, medium-, and low-security psychiatric services.