Non-Lethal Blood Sampling of Fish in the lab and Field With Methods for Dried Blood Plasma Spot Omic Analyses.

There is global acknowledgment that humane methods in animal research are a priority, but few environmental effects monitoring programs use nonlethal methods for fish. The goal of the present study was to determine the impacts of sampling small volumes of blood in larger-bodied fish on survival and healing. In addition to evaluating survival following blood sampling, we evaluated the utility of dried blood spots as an alternative for sample processing and storage in the field. In our approach, we housed 80 rainbow trout (Oncorhynchus mykiss) in our flow-through aquatic facility. We then anaesthetized using MS-222 and sampled 1 µl/g bw of blood via puncture of the caudal vasculature. We tested four different post-blood sampling treatments on the puncture wound: 1. application of liquid bandage; 2. a swab of betadine; 3. a swab of fish mucous; and 4. compared survival outcomes to a group where no post-treatment was performed (negative control). Overall, we observed 90% survival among all treatments, with the most effective approach being the negative control (100% survival). Based upon these results, we repeated the blood sampling with no-post treatment by housing 20 rainbow trout (not previously tested upon) in cages at a nearby creek and monitored survival for 2 weeks post sampling. The survival rate was 95% with full healing of the puncture site in all subjects. In addition to this, we tested the efficacy of dry blood spotting on proteomic, lipidomic and amino acid analysis as an alternative method for blood sample processing and storage. It was found that dried plasma spotting using parafilm in conjunction with a modified Bligh-Dyer extraction offered the best balance for good recovery of protein, lipid and amino acids relative to wet plasma and Noviplex dried plasma spot cards. In this article, we will present the detailed results of these combined studies and describe what we have determined to be the safest non-lethal blood sampling protocol.

Infant Midnasal Stenosis: Reliability of Nasal Metrics.

BACKGROUND AND PURPOSE: Midnasal stenosis is a poorly defined entity that may be a component of other conditions of nasal obstruction contributing to respiratory distress in infants. We sought to establish whether midnasal vault narrowing is a component of well-defined syndromes of nasal narrowing, such as bilateral choanal atresia and pyriform aperture stenosis, and to characterize the nasal anatomy of patients with syndromic craniosynostosis. MATERIALS AND METHODS: A convenience sample of patients with pyriform aperture stenosis, bilateral choanal atresia, and Apert and Crouzon syndromes with maxillofacial CT scans was identified. Patients with Pierre Robin Sequence were used as controls. Nasal measurements were performed at the pyriform aperture, choana, and defined midnasal points on axial and coronal CT scans. Intra- and interrater reliability was quantified with the intraclass correlation coefficient. T tests with Bonferroni adjustment were used to assess differences from controls. RESULTS: The study included 50 patients: Eleven had pyriform aperture stenosis, 10 had Apert and Crouzon syndromes, 9 had choanal atresia, and 20 were controls. Measurements in patients with pyriform aperture stenosis and Apert and Crouzon syndromes were narrower than those of controls at all measured points (P < .001). Measurements in patients with choanal atresia were only narrow in the posterior half of the nose (P < .001). The intra- and interrater reliability of midnasal and pyriform measurements was very good to excellent (intraclass correlation coefficient > 0.87). The choanal measurement was good (intraclass correlation coefficient = 0.76-0.77). CONCLUSIONS: Pyriform aperture stenosis, Apert and Crouzon patients were narrower at all measured points compared to controls. Bilateral choanal atresia patients were only narrower in the posterior half of the nose. More research is needed to evaluate the clinical implications of these radiographic findings.

Use of dispersion modelling for Environmental Impact Assessment of biological air pollution from composting: Progress, problems and prospects.

With the increase in composting asa sustainable waste management option, biological air pollution (bioaerosols) from composting facilities have become a cause of increasing concern due to their potential health impacts. Estimating community exposure to bioaerosols is problematic due to limitations in current monitoring methods. Atmospheric dispersion modelling can be used to estimate exposure concentrations, however several issues arise from the lack of appropriate bioaerosol data to use as inputs into models, and the complexity of the emission sources at composting facilities. This paper analyses current progress in using dispersion models for bioaerosols, examines the remaining problems and provides recommendations for future prospects in this area. A key finding is the urgent need for guidance for model users to ensure consistent bioaerosol modelling practices.

Delivering organisational adaptation through legislative mechanisms: Evidence from the Adaptation Reporting Power (Climate Change Act 2008).

There is increasing recognition that organisations, particularly in key infrastructure sectors, are potentially vulnerable to climate change and extreme weather events, and require organisational responses to ensure they are resilient and adaptive. However, detailed evidence of how adaptation is facilitated, implemented and reported, particularly through legislative mechanisms is lacking. The United Kingdom Climate Change Act (2008), introduced the Adaptation Reporting Power, enabling the Government to direct so-called reporting authorities to report their climate change risks and adaptation plans. We describe the authors' unique role and experience supporting the Department for Environment, Food and Rural Affairs (Defra) during the Adaptation Reporting Power's first round. An evaluation framework, used to review the adaptation reports, is presented alongside evidence on how the process provides new insights into adaptation activities and triggered organisational change in 78% of reporting authorities, including the embedding of climate risk and adaptation issues. The role of legislative mechanisms and risk-based approaches in driving and delivering adaptation is discussed alongside future research needs, including the development of organisational maturity models to determine resilient and well adapting organisations. The Adaptation Reporting Power process provides a basis for similar initiatives in other countries, although a clear engagement strategy to ensure buy-in to the process and research on its long-term legacy, including the potential merits of voluntary approaches, is required.

The burden of nonadherence among adults with asthma: a role for shared decision-making.

A shared approach to decision-making framework has been suggested for chronic disease management especially where multiple treatment options exist. Shared decision-making (SDM) requires that both physician and patients are actively engaged in the decision-making process, including information exchange; expressing treatment preferences; as well as agreement over the final treatment decision. Although SDM appears well supported by patients, practitioners and policymakers alike, the current challenge is to determine how best to make SDM a reality in everyday clinical practice. Within the context of asthma, adherence rates are poor and are linked to outcomes such as reduced asthma control, increased symptoms, healthcare expenditures, and lower patient quality of life. It has been suggested that SDM can improve treatment adherence and that ignoring patients' personal goals and preferences may result in reduced rates of adherence. Furthermore, understanding predictors of poor treatment adherence is a necessary step toward developing effective strategies to improve the patient-reported and clinically important outcomes. Here, we describe why a shared approach to treatment decision-making for asthma has the potential to be an effective tool for improving adherence, with associated clinical and patient-related outcomes. In addition, we explore insights into the reasons why SDM has not been implemented into routine clinical practice.

Sensitivity of predicted bioaerosol exposure from open windrow composting facilities to ADMS dispersion model parameters.

Bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are not well understood, and require improved exposure classification. Dispersion modelling has great potential to improve exposure classification, but has not yet been extensively used or validated in this context. We present a sensitivity analysis of the ADMS dispersion model specific to input parameter ranges relevant to bioaerosol emissions from open windrow composting. This analysis provides an aid for model calibration by prioritising parameter adjustment and targeting independent parameter estimation. Results showed that predicted exposure was most sensitive to the wet and dry deposition modules and the majority of parameters relating to emission source characteristics, including pollutant emission velocity, source geometry and source height. This research improves understanding of the accuracy of model input data required to provide more reliable exposure predictions.

Integrating horizon scanning and strategic risk prioritisation using a weight of evidence framework to inform policy decisions.

Poor connection between data on emerging issues and credible policy decisions continues to challenge governments, and is only likely to grow as demands on time and resources increase. Here we summarise recent efforts to integrate horizon scanning and risk prioritisation approaches to better connect emerging issues to the political discourse on environmental and food-related issues. Our categorisation of insights including potential future risks and opportunities to inform policy discussions has emerged from a structured three-year programme of horizon scanning for a UK pan-governmental futures partnership led by the Department for Environment, Food and Rural Affairs (Defra). Our efforts to integrate horizon scanning and risk prioritisation, utilising a qualitative weight of evidence framework, has created a systematic process for identifying all signals of potential future change with significant impact for the strategic mission and underlying values of policy actors. Our approach encourages an exploration of factors out of the control of organisations, recognising that resilience depends on the flexibility of management strategies and the preparedness to deal with a variety of unexpected outcomes. We discuss how this approach addresses key cultural and evaluative challenges that policy actors have had in embedding horizon scanning in evidence-based policy processes, and suggest further developments to build confidence in the use of horizon scanning for strategic planning.

A randomised phase IIb trial to assess the efficacy of ReCharge ice cream in preventing chemotherapy-induced diarrhoea.

PURPOSE: Chemotherapy-induced diarrhoea (CID) has a significant impact. A medicinal food product (ReCharge) containing iron-saturated lactoferrin and anhydrous milk fat reduces the detrimental effects of chemotherapy on the gut in animals. We report results of a randomised blinded placebo-controlled phase IIb trial investigating the efficacy and safety of ReCharge in preventing CID. METHODS: Eligible patients were adults due to start the first cycle of a 2- or 3-week-cycle chemotherapy regimen, had an Eastern Cooperative Oncology Group (ECOG) status of 3 or less, had adequate haematological, liver and renal function and provided written informed consent. Patients (197) were randomised to ReCharge or placebo. They consumed 100-g study product for 2 weeks before and 6 weeks after starting chemotherapy, completed daily diaries for 8 weeks and attended clinic visits until 12 weeks (2-week cycles) or 14 weeks (3-week cycles). The primary outcome was days with CID. RESULTS: The mean number of days with diary-recorded CID was marginally but not statistically significantly lower on ReCharge than placebo (-2.0, 95 % CI (-4.7 to 0.7), p = 0.2). The proportion reporting diarrhoea in the previous cycle at the clinic visit was 30 % lower (p = 0.012) on ReCharge. Missing diary data may have contributed to the discrepancy. No significant differences were found in quality of life or other adverse events. CONCLUSIONS: We found no clear evidence that ReCharge reduced CID as measured by patient self-report diary. The converse finding of benefit as recorded at clinic visits and incomplete adherence to diary completion indicates that further research is required into methods for measuring CID.

25-hydroxy vitamin D levels are associated with childhood asthma in a population-based study in Peru.

BACKGROUND: Vitamin D deficiency may be associated with an increased risk of asthma. OBJECTIVE: We studied the association between 25-hydroxy (25-OH) vitamin D deficiency and asthma prevalence in two Peruvian populations close to the equator but with disparate degrees of urbanization. METHODS: We conducted a population-based study in 1441 children in two communities in Peru, of which 1134 (79%) provided a blood sample for 25-OH vitamin D analysis. RESULTS: In these 1134 children, mean age was 14.8 years; 52% were boys; asthma and atopy prevalence was 12% in Lima vs. 3% in Tumbes (P < 0.001) and 59% in Lima vs. 41% in Tumbes (P < 0.001), respectively; and, mean 25-OH vitamin D level was 20.8 ng/mL in Lima vs. 30.1 ng/mL in Tumbes (P < 0.001). Prevalence of 25-OH vitamin D deficiency (< 20 ng/mL) was 47% in Lima vs. 7% in Tumbes (P < 0.001). In multi-variable logistic regression, we found that lower 25-OH vitamin D levels were associated with an increased odds of asthma (OR = 1.7 per each 10 ng/mL decrease in 25-OH vitamin D levels, 95% CI 1.2-2.6; P < 0.01). In stratified analyses, the association between lower 25-OH vitamin D levels and asthma was limited to children with atopy (OR = 2.2, 95% CI 1.3-3.6) and not in those without atopy (OR = 0.9, 95% CI 0.5-2.0). We did not find associations between 25-OH vitamin D levels and other clinical biomarkers for asthma, including exhaled nitric oxide, total serum IgE and pulmonary function. CONCLUSION AND CLINICAL RELEVANCE: Both asthma and 25-OH vitamin D deficiency were common among children living in Lima (latitude = 12.0 °S) but not among those in Tumbes (3.6 °S). The relationship between 25-OH vitamin D deficiency and asthma was similar in both sites and was limited among children with atopy. Future supplementation trials may need to consider stratification by atopy at the time of design.

The management of the surgical complications of HELLP syndrome.

INTRODUCTION: Complications from HELLP (Haemolysis, Elevated Liver enzymes and Low Platelet) syndrome may present as an emergency to any surgeon. We review the ten-year experience of a tertiary hepatobiliary centre managing HELLP patients. Three selected cases are described to highlight our management strategy and a systematic review of the recent literature is presented. METHODS: All patients with HELLP syndrome were identified from a prospectively maintained database and their details collated. Subsequently, a detailed search of PubMed was carried out to identify all case series of HELLP syndrome in the literature in the English language since 1999. RESULTS: On review of 1,002 cases, 10 patients were identified with surgical complications of HELLP syndrome. Seven of these patients had a significant liver injury. Only three of these required surgical intervention for liver injury although four other patients required surgical intervention for other complications. There was no maternal mortality in this series. Review of the literature identified 49 cases in 31 publications. The management approaches of these patients were compared with ours. CONCLUSIONS: We have presented a large series of patients with surgical complications resulting from HELLP syndrome managed without maternal mortality. This review has confirmed that haemodynamically stable patients with HELLP syndrome associated hepatic rupture can be conservatively treated successfully. However, in unstable patients, perihepatic packing and transfer to a specialist liver unit is recommended.

Relationship between documentation method and quality of chronic disease visit notes.

OBJECTIVE: To assses the relationship between methods of documenting visit notes and note quality for primary care providers (PCPs) and specialists, and to determine the factors that contribute to higher quality notes for two chronic diseases. METHODS: Retrospective chart review of visit notes at two academic medical centers. Two physicians rated the subjective quality of content areas of the note (vital signs, medications, lifestyle, labs, symptoms, assessment & plan), overall quality, and completed the 9 item Physician Documentation Quality Instrument (PDQI-9). We evaluated quality ratings in relation to the primary method of documentation (templates, free-form or dictation) for both PCPs and specialists. A one factor analysis of variance test was used to examine differences in mean quality scores among the methods. RESULTS: A total of 112 physicians, 71 primary care physicians (PCP) and 41 specialists, wrote 240 notes. For specialists, templated notes had the highest overall quality scores (p≤0.001) while for PCPs, there was no statistically significant difference in overall quality score. For PCPs, free form received higher quality ratings on vital signs (p = 0.01), labs (p = 0.002), and lifestyle (p = 0.002) than other methods; templated notes had a higher rating on medications (p≤0.001). For specialists, templated notes received higher ratings on vital signs, labs, lifestyle and medications (p = 0.001). DISCUSSION: There was no significant difference in subjective quality of visit notes written using free-form documentation, dictation or templates for PCPs. The subjective quality rating of templated notes was higher than that of dictated notes for specialists. CONCLUSION: As there is wide variation in physician documentation methods, and no significant difference in note quality between methods, recommending one approach for all physicians may not deliver optimal results.

Coherence and modality of driven interlayer-coupled magnetic vortices.

The high-frequency dynamics of mode-coupled magnetic vortices have generated great interest for spintronic technologies, such as spin-torque nano-oscillators. While the spectroscopic characteristics of vortex oscillators have been reported, direct imaging of driven coupled magnetic quasi-particles is essential to the fundamental understanding of the dynamics involved. Here, we present the first direct imaging study of driven interlayer coaxial vortices in the dipolar- and indirect exchange-coupled regimes. Employing in situ high-frequency excitation with Lorentz microscopy, we directly observe the steady-state orbital amplitudes in real space with sub-5 nm spatial resolution. We discuss the unique frequency response of dipolar- and exchange-coupled vortex motion, wherein mode splitting and locking demonstrates large variations in coherent motion, as well as detail the resultant orbital amplitudes. This provides critical insights of the fundamental features of collective vortex-based microwave generators, such as their steady-state amplitudes, tunability and mode-coupled motion.

Morphological classification of bioaerosols from composting using scanning electron microscopy.

This research classifies the physical morphology (form and structure) of bioaerosols emitted from open windrow composting. Aggregation state, shape and size of the particles captured are reported alongside the implications for bioaerosol dispersal after release. Bioaerosol sampling took place at a composting facility using personal air filter samplers. Samples were analysed using scanning electron microscopy. Particles were released mainly as small (<1 µm) single, spherical cells, followed by larger (>1 µm) single cells, with aggregates occurring in smaller proportions. Most aggregates consisted of clusters of 2-3 particles as opposed to chains, and were <10 µm in size. No cells were attached to soil debris or wood particles. These small single cells or small aggregates are more likely to disperse further downwind from source, and cell viability may be reduced due to increased exposure to environmental factors.

Regulators as agents: modelling personality and power as evidence is brokered to support decisions on environmental risk.

Complex regulatory decisions about risk rely on the brokering of evidence between providers and recipients, and involve personality and power relationships that influence the confidence that recipients may place in the sufficiency of evidence and, therefore, the decision outcome. We explore these relationships in an agent-based model; drawing on concepts from environmental risk science, decision psychology and computer simulation. A two-agent model that accounts for the sufficiency of evidence is applied to decisions about salt intake, animal carcass disposal and radioactive waste. A dynamic version of the model assigned personality traits to agents, to explore their receptivity to evidence. Agents with 'aggressor' personality sets were most able to imbue fellow agents with enhanced receptivity (with 'avoider' personality sets less so) and clear confidence in the sufficiency of evidence. In a dynamic version of the model, when both recipient and provider were assigned the 'aggressor' personality set, this resulted in 10 successful evidence submissions in 71 days, compared with 96 days when both agents were assigned the 'avoider' personality set. These insights suggest implications for improving the efficiency and quality of regulatory decision making by understanding the role of personality and power.

Effective drinking water collaborations are not accidental: interagency relationships in the international water utility sector.

The role that deficient institutional relationships have played in aggravating drinking water incidents over the last 30 years has been identified in several inquiries of high profile drinking water safety events, peer-reviewed articles and media reports. These indicate that collaboration between water utilities and public health agencies (PHAs) during normal operations, and in emergencies, needs improvement. Here, critical elements of these interagency collaborations, that can be integrated within the corporate risk management structures of water utilities and PHAs alike, were identified using a grounded theory approach and 51 semi-structured interviews with utility and PHA staff. Core determinants of effective interagency relationships are discussed. Intentionally maintained functional relationships represent a key ingredient in assuring the delivery of safe, high quality drinking water.

Scientific commentary: Strategic analysis of environmental policy risks--heat maps, risk futures and the character of environmental harm.

We summarise our recent efforts on the policy-level risk appraisal of environmental risks. These have necessitated working closely with policy teams and a requirement to maintain crisp and accessible messages for policy audiences. Our comparative analysis uses heat maps, supplemented with risk narratives, and employs the multidimensional character of risks to inform debates on the management of current residual risk and future threats. The policy research and ensuing analysis raises core issues about how comparative risk analyses are used by policy audiences, their validation and future developments that are discussed in the commentary below.

A randomized phase II study comparing capecitabine alone with capecitabine and oral cyclophosphamide in patients with advanced breast cancer-cyclox II.

BACKGROUND: Capecitabine and cyclophosphamide are active in patients with advanced breast cancer, have non-overlapping toxic effects and synergy pre-clinically. We explored the efficacy and toxic effect of an all-oral combination of capecitabine with cyclophosphamide versus capecitabine alone in a multicentre, randomized, phase II study. PATIENTS AND METHODS: Patients with locally advanced or metastatic breast cancer were randomized to treatment with capecitabine given continuously (666 mg/m(2) b.i.d. days 1-28) alone (C) or with oral cyclophosphamide (100 mg/m(2) days 1-14 of a 28-day cycle) (CCy) for up to six cycles. RESULTS: Eighty-two patients were randomized. There was no complete response. The proportions with partial response were 36% on C and 44% on CCy, a difference of 7.9% [95% confidence interval (CI) -13.4 to 29.1]. Significant toxic effect was uncommon: grade ≥3 diarrhoea in 4 (10%) versus 1 (3%) patients; grade ≥3 fatigue in 2 (5%) versus 5 patients (13%) and grade ≥2 hand-foot syndrome in 7 (17%) versus 11 (28%) patients receiving C versus CCy, respectively. Median progression-free survival was 3.1 months on C and 6.9 months on CCy, not significantly different statistically. There was no difference in overall survival. CONCLUSION: The difference in tumour response suggests a reasonable chance that CCy is superior to C alone.

Better by design: rethinking interventions for better environmental regulation.

Better regulation seeks to extend existing policy and regulatory outcomes at less burden for the actors involved. No single intervention will deliver all environmental outcomes. There is a paucity of evidence on what works why, when and with whom. We examine how a sample (n=33) of policy makers select policy and regulatory instruments, through a case study of the Department for Environment, Food and Rural Affairs (Defra), UK. Policy makers have a wide range of instruments at their disposal and are seeking ways to harness the influence of non-governmental resources to encourage good environmental behaviour. The relevance of each influence varies as risk and industry characteristics vary between policy areas. A recent typology of policy and regulatory instruments has been refined. Direct regulation is considered necessary in many areas, to reduce environmental risks with confidence and to tackle poor environmental performance. Co-regulatory approaches may provide important advantages to help accommodate uncertainty for emerging policy problems, providing a mechanism to develop trusted evidence and to refine objectives as problems are better understood.

Direct dynamic imaging of non-adiabatic spin torque effects.

Spin-transfer torques offer great promise for the development of spin-based devices. The effects of spin-transfer torques are typically analysed in terms of adiabatic and non-adiabatic contributions. Currently, a comprehensive interpretation of the non-adiabatic term remains elusive, with suggestions that it may arise from universal effects related to dissipation processes in spin dynamics, while other studies indicate a strong influence from the symmetry of magnetization gradients. Here we show that enhanced magnetic imaging under dynamic excitation can be used to differentiate between non-adiabatic spin-torque and extraneous influences. We combine Lorentz microscopy with gigahertz excitations to map the orbit of a magnetic vortex core with <5 nm resolution. Imaging of the gyrotropic motion reveals subtle changes in the ellipticity, amplitude and tilt of the orbit as the vortex is driven through resonance, providing a robust method to determine the non-adiabatic spin torque parameter ß=0.15±0.02 with unprecedented precision, independent of external effects.