The policy chicken and the science egg. Has applied ecology failed the transgenic crops debate?

Ecology has a long history of research relevant to and impacting on real-world issues. Nonetheless problems of communication remain between policy-makers and scientists because they tend to work at different levels of generality (policy deals with broad issues, science prefers specific questions), and complexity (policy-makers want simple answers, ecologists tend to offer multi-factorial solutions) and to different timescales (policy-makers want answers tomorrow, ecologists always seem to want more time). These differences are not unique to the debate about the cultivation of transgenic crops. Research on gene flow is used to illustrate how science and policy are intimately bound together in a value-laden, iterative and messy process unlike that characterised by the 'encounter problem-do science-make policy' model. It also demonstrates how the gap between science and policy is often characterised by value-laden language. Scientists involved in ERA for transgenic crops may find their engagement with policy- and decision-makers clouded by misunderstanding about what one should expect from the other. Not the least of these, that science can define harm, is explored in a discussion of the U.K. Farm Scale Evaluations of herbicide-tolerant GM crops. The varied responses to these extensive trials highlight the problems of linking specific scientific experiments with broad policy objectives. The problems of applied ecology in the transgenic crops debate are not unique but may differ from other areas of environmental policy in the intense politicisation of the debate, the emphasis on assessment of risk and the particularly broad policy objectives.

EU sampling strategies for the detection of veterinary drug residues in aquaculture species: are they working?

Over the past 50 years, the culture of aquatic species in controlled conditions to enhance production has grown in importance and now provides nearly 50% of the world's seafood supply. In part, this expansion has been made possible by the use of antibiotics, antifungals, and other veterinary medicines to control disease and improve welfare. Despite guidelines being available, the sampling programmes for drug residue surveillance of aquaculture products recommended by the CODEX Alimentarius Commission were withdrawn in 2008 and put under review. Directive 96/23/EC sets out legislation to govern how sampling programmes for drug residue surveillance should be conducted within the EU. This directive applies both to produce raised within the EU and also imported products from third countries. This communication examines the existing EU sampling regimen for aquaculture products and comments on its possible application in a global context. We examine UK statutory sampling data that, while indicating the effectiveness of the directive, also suggests that the directive may lead to unnecessary sampling. Regarding imports, examination of the Rapid Alert System for Food and Feed (RASFF) database using process control charts and statistical modelling suggests that the sampling regimen described in the directive is effective but not sufficiently flexible for the range of aquaculture practices that exist. Limitations of the directive, datasets, and practices are further discussed.

Bystander CPR in south east Scotland increases over 16 years.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a leading cause of mortality and serious neurological disability across Europe. Without immediate bystander cardiopulmonary resuscitation (CPR), chances of survival are minimal. Despite community initiatives to increase the number of trained CPR providers, the effectiveness of these measures remains unknown and the proportion of OHCA patients receiving bystander CPR in the United Kingdom yet to be established. We sought to identify the change in the rate of bystander CPR in south east Scotland over a 16-year period. METHODS: Retrospective cohort study of all adult non-traumatic OHCA in south east Scotland from 1 January 1992 to 31 December 2007 using the Heartstart Scotland database. RESULTS: 7928 OHCA were included. The proportion of patients receiving bystander CPR increased from 34% in 1992 to 52% in 2007 (p for trend <0.0001). The rate of CPR from bystanders, spouses and from relatives increased significantly over the study period. Patients arresting at home received significantly less bystander CPR than those arresting away from home (39% vs 52%, p<0.0001) regardless of age or sex. CONCLUSION: There has been a significant increase in bystander CPR in south east Scotland during the 16-year period. Bystander CPR is associated with an increased rate of survival and targeted CPR training for relatives of patients at risk of sudden cardiac death may be beneficial.

A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial.

OBJECTIVES: To determine whether non-invasive ventilation reduces mortality and whether there are important differences in outcome by treatment modality. DESIGN: Multicentre open prospective randomised controlled trial. SETTING: Patients presenting with severe acute cardiogenic pulmonary oedema in 26 emergency departments in the UK. PARTICIPANTS: Inclusion criteria were age > 16 years, clinical diagnosis of acute cardiogenic pulmonary oedema, pulmonary oedema on chest radiograph, respiratory rate > 20 breaths per minute, and arterial hydrogen ion concentration > 45 nmol/l (pH < 7.35). INTERVENTIONS: Patients were randomised to standard oxygen therapy, continuous positive airway pressure (CPAP) (5-15 cmH2O) or non-invasive positive pressure ventilation (NIPPV) (inspiratory pressure 8-20 cmH2O, expiratory pressure 4-10 cmH2O) on a 1:1:1 basis for a minimum of 2 hours. MAIN OUTCOME MEASURES: The primary end point for the comparison between NIPPV or CPAP and standard therapy was 7-day mortality. The composite primary end point for the comparison of NIPPV and CPAP was 7-day mortality and tracheal intubation rate. Secondary end points were breathlessness, physiological variables, intubation rate, length of hospital stay and critical care admission rate. Economic evaluation took the form of a cost-utility analysis, taken from an NHS (and personal social services) perspective. RESULTS: In total, 1069 patients [mean age 78 (SD 10) years; 43% male] were recruited to standard therapy (n = 367), CPAP [n = 346; mean 10 (SD 4) cmH2O] or NIPPV [n = 356; mean 14 (SD 5)/7 (SD 2) cmH2O]. There was no difference in 7-day mortality for standard oxygen therapy (9.8%) and non-invasive ventilation (9.5%; p = 0.87). The combined end point of 7-day death and intubation rate was similar, irrespective of non-invasive ventilation modality (CPAP 11.7% versus NIPPV 11.1%; p = 0.81). Compared with standard therapy, non-invasive ventilation was associated with greater reductions (treatment difference, 95% confidence intervals) in breathlessness (visual analogue scale score 0.7, 0.2-1.3; p = 0.008) and heart rate (4/min, 1-6; p = 0.004) and improvement in acidosis (pH 0.03, 0.02-0.04; p < 0.001) and hypercapnia (0.7 kPa, 0.4-0.9; p < 0.001) at 1 hour. There were no treatment-related adverse events or differences in other secondary outcomes such as myocardial infarction rate, length of hospital stay, critical care admission rate and requirement for endotracheal intubation. Economic evaluation showed that mean costs and QALYs up to 6 months were 3023 pounds and 0.202 for standard therapy, 3224 pounds and 0.213 for CPAP, and 3208 pounds and 0.210 for NIPPV. Modelling of lifetime costs and QALYs produced values of 15,764 pounds and 1.597 for standard therapy, 17,525 pounds and 1.841 for CPAP, and 17,021 pounds and 1.707 for NIPPV. These results suggest that both CPAP and NIPPV accrue more QALYs but at higher cost than standard therapy. However, these estimates are subject to substantial uncertainty. CONCLUSIONS: Non-invasive ventilatory support delivered by either CPAP or NIPPV safely provides earlier improvement and resolution of breathlessness, respiratory distress and metabolic abnormality. However, this does not translate into improved short- or longer-term survival. We recommend that CPAP or NIPPV should be considered as adjunctive therapy in patients with severe acute cardiogenic pulmonary oedema in the presence of severe respiratory distress or when there is a failure to improve with pharmacological therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07448447.

Syncope management in the UK and Republic of Ireland.

AIMS: To establish the current practice of emergency department (ED) management of syncope in the UK and Republic of Ireland. METHODS: A survey of "major" or "intermediate" size ED in the UK and Republic of Ireland conducted by postal and telephone questionnaire. RESULTS: 177 (70%) ED responded. 32 (18%) ED have syncope guidelines, which are based on a range of existing guidelines. 97 ED (55%) have an observation ward or clinical decision unit and 48 (49%) of these admit syncope patients to these units. 32 ED (18%) have access to a specialist syncope outpatient clinic. This is most likely to be run by general practitioner specialists (43%) or general physicians (24%). 81% of ED felt that improved research-based guidelines would be useful when managing syncope patients. CONCLUSION: The ED management of syncope patients in the UK and Republic of Ireland is varied. Only 18% of ED have specific guidelines for managing this difficult condition and only 18% have access to a specialist syncope clinic. A robust consensus UK syncope guideline is clearly required.

The Prediction of Risk In Syncope using ECG characteristics (PRISE) pilot study: can heart rate variability be used to predict risk in patients presenting to the emergency department with syncope?

AIM: This study was conducted as a feasibility pilot for the Prediction of Risk In Syncope using ECG characteristics (PRISE) study. The secondary aim was to determine whether heart rate variability (HRV) characteristics may be useful to distinguish low and high-risk syncope patients. METHODS: Adult patients presenting to the emergency department (ED) with syncope over a one-month period underwent a 5-minute 12-lead ECG. Study patients were assigned high, medium or low-risk status according to the ED's existing syncope guidelines as well as one of four likely diagnostic categories. ECG signals from all patients were then analysed and time domain HRV characteristics were derived using WelchAllyn's Cardioperfect interpretation software. A control group of patients was also recruited. RESULTS: Over a 4-week period in July 2007, 32 patients were recruited into the study group and 23 into the control group. ECG tracings of five study group patients were not suitable for analysis. According to the ED's existing syncope guidelines there were nine low-risk, 12 medium-risk and six high-risk patients with diagnostic categories as follows: postural hypotension, five; vasovagal, 16; cardiac, five and other, one. Patients with cardiac syncope had greater mean values for all HRV characteristics except NN number and NN minimum; however, with overlapping confidence intervals. Low-risk patients were more likely to be younger than medium and high-risk patients. No HRV parameters showed any significant differences. CONCLUSIONS: Measuring HRV in the acute ED setting is feasible. If patients with cardiac and neurocardiogenic syncope have different HRV characteristics then it could be useful to determine a patient's underlying cause of syncope in the ED, which would allow earlier decision-making.

Validation and application of Caco-2 assays for the in vitro evaluation of development candidate drugs as substrates or inhibitors of P-glycoprotein to support regulatory submissions.

1. An understanding of the role that transporters, in particular P-glycoprotein (P-gp), can play in the absorption, distribution, metabolism and excretion (ADME) of candidate drugs, and an assessment of how these processes might impact on toxicity and the potential for drug-drug interactions in the clinic, is required to support drug development and registration. It is therefore necessary to validate preclinical assays for the in vitro evaluation of candidate drugs as substrates or inhibitors of human P-gp. 2. The present study has characterized a Caco-2 cell monolayer model by determining the bi-directional apparent permeabilities and efflux ratios of the known P-gp substrates ([(3)H]-digoxin, [(3)H]-ketoconazole, [(3)H]-verapamil, [(3)H]-quinidine, dipyridamole and loratidine; 1-100 microM) a non-substrate ([(3)H]-propranolol; 10 microM), or by determining the inhibitory potencies (IC(50)) of inhibitors (verapamil, ketoconazole, quinidine, dipyridamole and probenecid; 0.1-100 microM) on the basolateral-to-apical transport of [(3)H]-digoxin (5 microM), in order to validate methodologies for the identification of substrates or inhibitors of P-gp, respectively. 3. The reproducibility of the [(3)H]-digoxin or verapamil data determined from replicate monolayers across different cell passages indicates that the functional expression of P-gp is consistent across the range of passages (25-40) utilized for transport experiments and that the determination of bi-directional apparent permeability, or IC(50) for inhibition of P-gp, respectively, need only be performed on one occasion for a test compound. [(3)H]-digoxin and [(3)H]-propranolol or verapamil and probenecid were considered to be appropriate positive and negative controls of P-gp-mediated transport, or inhibition of P-gp, respectively, to ensure performance of the assays when assessing candidate drugs. Additionally, the low IC(50) values determined for ketoconazole and quinidine indicated that these inhibitors were suitable to use to confirm the role of P-gp in the efflux of a test compound. 4. These validated Caco-2 assays are robust, reproducible and suitable for routine in vitro evaluation of candidate drugs. They have been successfully applied to development projects resulting in the identification of two candidate drugs as substrates and inhibitors of P-gp, whereas a third was neither a substrate nor an inhibitor of this transporter.

Emergency department evaluation of sudden, severe headache.

AIM: To assess the clinical management of adults presenting with sudden, severe headache. METHODS: We retrospectively reviewed the medical records of consecutive adults presenting with sudden, severe headache to the emergency department (ED) or medical admissions unit at one teaching hospital. RESULTS: Of 12 025 consecutive attendances over 3 months, 91 adults (0.8%, 95% CI 0.6-0.9%) presented with sudden severe headache. Documentation of time to peak headache intensity and headache duration was complete in only 33% of cases. Brain computed tomography was performed in each of the 29 patients (33%) in whom it appeared indicated for the investigation of headaches peaking within 5 min and lasting more than 1 h, as well as 11 patients (13%) who did not meet these criteria. Lumbar puncture was attempted in every patient for whom it appeared indicated (although it was unsuccessful and abandoned on three of 24 patients), as well as one patient in whom it appeared not to be indicated. When subarachnoid haemorrhage was suspected, 81% of patients had spectrophotometry. Of the patients, 52 (60%) were given a specific diagnosis, 17 (33%) of whom were given a diagnosis despite an apparently insufficient history. A further 12 (14%) could have been diagnosed if the International Headache Society classification had been applied to the documented history. Neurological advice was sought for only 20 patients (23%). CONCLUSION: Patients with sudden, severe headache might benefit if EDs used simple protocols, emphasizing the crucial elements of history and examination, appropriate investigation and targeted consultation with neurologists.

In vivo protein transduction to the CNS.

Proteins and peptides are useful research and therapeutic tools, however applications are limited because delivery to the desired location is not easily achievable. There are two hurdles in protein/peptide delivery to the brain: the blood-brain barrier and intracellular penetration. Penetration to both brain and the intracellular space can be achieved by adjusting hydrophilicity, and small molecule pharmacological agents have been successfully developed using this approach. But with proteins and peptides, it is difficult to modify the hydrophilicity without influencing biological functions. Trans-acting factor protein from the human immunodeficiency virus contains a highly conserved cationic peptide sequence necessary for transduction across the cell membrane. While trans-acting factor peptide has been used for in vitro protein transduction, its in vivo application is very limited because it is rapidly degraded by proteolysis. Polyethylenimine is a chemically synthesized small molecule cationization agent; the charge density is greater than a peptide-based cationic cluster such as trans-acting factor, and it is resistant to proteolysis in vivo. We first tested intracellular protein transduction following direct brain injection in mice using polyethylenimine-conjugated green fluorescence protein and beta-galactosidase (molecular weights 29 and 540 kDa, respectively). Polyethylenimine-conjugates penetrated to the intracellular space immediately surrounding the injection site within one hour. We further tested polyethylenimine-mediated protein transduction following intranasal administration, which bypasses the blood-brain barrier. Polyethylenimine-conjugates in pH 7.5 solution did not reach the brain, probably because the polyethylenimine-conjugates penetrated into the intracellular space where first exposed to the tissue, i.e. at the nasal mucosae. We temporarily reduced the electrostatic interaction between cationized polyethylenimine-conjugates and cellular surfaces by adjusting the pH to 4.5; solution rapidly reached the brain and penetrated to the intracellular space. This study suggests that polyethylenimine is a useful protein transduction agent in the brain in vivo, and adjusting cationic charge interaction can determine the extent of brain penetration.

Monitoring the development of intertidal habitats on former agricultural land after the managed realignment of coastal defences at Tollesbury, Essex, UK.

The managed realignment of coastal defences and subsequent creation of intertidal habitats is one of several 'soft' engineering options that could reduce the costs of maintaining embankments and at the same time deliver environmental benefits. The managed realignment at Tollesbury was one of the first in the UK, undertaken as an experimental test case to improve understanding of the practical techniques and processes involved. Independent studies were undertaken on the development of soils, benthic invertebrates and vegetation within the site in addition to methods of enhancing the process of natural colonisation of saltmarsh plants. Bathymetric and vegetation monitoring were undertaken on the adjacent estuary to determine any breach effect that may be attributed to the realignment. This paper summarises the results from the vegetation, sedimentation and invertebrate monitoring and discusses the implications for other managed realignment schemes in the UK.

Epidemiology, clinical characteristics, and management of adults referred to a teaching hospital first seizure clinic.

BACKGROUND: There are scarce data describing the epidemiology, clinical characteristics, and management of adults who suffer a suspected first seizure. AIM: To describe the epidemiology, clinical characteristics, and management of adults with a suspected first seizure who are referred to a teaching hospital first seizure clinic over a one year period. DESIGN: Prospective descriptive study. METHODS: Data were collected on consecutive adults referred to the Royal Infirmary of Edinburgh between 4 February 2003 and 10 February 2004. RESULTS: 232 patients were referred to the first seizure clinic. Median age was 32 years; 53% of patients were male. Lower socioeconomic groups were more likely to present with a suspected first seizure. Nineteen per cent of patients were admitted to hospital after their suspected seizure episode. Appropriate driving advice was reported in 64% of cases. Seventy two per cent of patients were offered a first seizure clinic appointment within six weeks of referral. Nine per cent of patients had a subsequent seizure while awaiting review. Fifty two per cent of patients were confirmed as having a first seizure at the clinic, of which 56% were provoked by alcohol, recreational drugs, or sleep deprivation. Electroencephalography and computed tomography of the brain were the most common investigations ordered at the first seizure clinic (22% and 22% of patients respectively). CONCLUSION: Adults who suffer a suspected first seizure, and who make a full neurological recovery, can be safely managed as an outpatient. Around half of these patients will have a specialist diagnosis of first seizure and alcohol will be a common precipitating factor.

Early management of adults with an uncomplicated first generalised seizure.

A literature review of first seizures in adults was performed and a management algorithm was constructed. This review highlights the importance of a thorough history and examination, routine biochemistry and haematology, an electrocardiogram, selected neuroimaging, discharge planning with driving and lifestyle advice, and follow-up in a specialist clinic.

Prehospital trauma management: a national study of paramedic activities.

OBJECTIVES: The benefits of prehospital trauma management remain controversial. This study aimed to compare the processes of care and outcomes of trauma patients treated by paramedics, who are trained in advanced prehospital trauma care, with those treated by ambulance technicians. METHODS: A six year prospective study was conducted of adult trauma patients attended to by the Scottish Ambulance Service and subsequently admitted to hospital. Prehospital times, interventions, triage, and outcomes were compared between patients treated by paramedics and those treated by technicians. RESULTS: Paramedics attended more severely injured patients (16.5% versus 13.9%, p<0.001); they attended a higher proportion of patients with penetrating trauma (6.6% versus 5.7%, p = 0.014) and had longer prehospital times. Patients managed by paramedics were more likely to be taken to the intensive care unit, operating theatre or mortuary, (11.2% versus 7.8%, p<0.001) and had higher crude mortality rates (5.3% versus 4.5%, p = 0.07). However, no difference in mortality between the two groups was noted when corrected for age, Glasgow coma score and injury severity score. CONCLUSIONS: This large scale national study shows that paramedics show good triage skills and clinical judgement when managing trauma patients. However, the value of the individual interventions they perform could not be ascertained. Further controlled trials are necessary to determine the true benefits of advanced prehospital trauma life support.

A1 and A2 transitions in superfluid 3He in 98% porosity aerogel.

Superfluid 3He in high porosity aerogel is the system in which the effects of static impurities on a p-wave superfluid can be investigated in a systematic manner. We performed shear acoustic impedance measurements on this system (98% porosity aerogel) in the presence of magnetic fields up to 15 T at the sample pressures of 28.4 and 33.5 bars. We observed the splitting of the superfluid transition into two transitions in high fields in both bulk and liquid in aerogel. The field dependence of the splitting in aerogel resembles that of the bulk superfluid 3He caused by the presence and growth of the A1 phase. Our results provide the first evidence of the A1 phase in superfluid (3)He/aerogel.

Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema.

BACKGROUND: Continuous positive airways pressure (CPAP) and bilevel non-invasive ventilation may have beneficial effects in the treatment of patients with acute cardiogenic pulmonary oedema. The efficacy of both treatments was assessed in the UK emergency department setting, in a randomised comparison with standard oxygen therapy. METHODS: Sixty patients presenting with acidotic (pH<7.35) acute, cardiogenic pulmonary oedema, were randomly assigned conventional oxygen therapy, CPAP (10 cm H(2)O), or bilevel ventilation (IPAP 15 cm H(2)O, EPAP 5 cm H(2)O) provided by a standard ventilator through a face mask. The main end points were treatment success at two hours and in-hospital mortality. Analyses were by intention to treat. RESULTS: Treatment success (defined as all of respiratory rate<23 bpm, oxygen saturation of>90%, and arterial blood pH>7.35 (that is, reversal of acidosis), at the end of the two hour study period) occurred in three (15%) patients in the control group, seven (35%) in the CPAP group, and nine (45%) in the bilevel group (p = 0.116). Fourteen (70%) of the control group patients survived to hospital discharge, compared with 20 (100%) in the CPAP group and 15 (75%) in the bilevel group (p = 0.029; Fisher's test). CONCLUSIONS: In this study, patients presenting with acute cardiogenic pulmonary oedema and acidosis, were more likely to survive to hospital discharge if treated with CPAP, rather than with bilevel ventilation or with conventional oxygen therapy. There was no relation between in hospital survival and early physiological changes. Survival rates were similar to other studies despite a low rate of endotracheal intubation.

Olfactory identification is impaired in clinic-based patients with vascular dementia and senile dementia of Alzheimer type.

AIMS: It is now well established that there are abnormalities in the sense of smell in patients suffering from Alzheimer's disease (AD). They have both raised olfactory thresholds and impaired odour identification. The situation in vascular dementia is unclear. We used the University of Pennsylvania Smell Identification Test (UPSIT), a 40-item, forced choice, cued, 'scratch-and- sniff' test, to examine olfactory identification in vascular dementia and to determine whether it would differentiate the disorder from AD and normal elderly. METHODS: We investigated three matched subject groups: 13 people having a Cambridge Examination for Mental Disorders in the Elderly (CAMDEX) diagnosis of definite senile dementia of Alzheimer type, 13 having a CAMDEX diagnosis of definite vascular dementia and 13 non-cognitively impaired controls. The subjects were then tested with the UPSIT in their own home by an independent blind researcher to see if the test could distinguish the different diagnostic groups in this setting. RESULTS: The median UPSIT score was 30 (out of a maximum of 40) for controls, 12 for the vascular group and 15 for the AD group. The difference was significant (p = 0.05) between both demented groups and the normal controls. Similarly there was a significant difference in the UPSIT score between the AD group and controls (p = 0.001) and between the vascular dementia group and controls (p = 0.001), but there was no significant difference between the AD group and the vascular dementia group. The UPSIT score correlated strongly with the degree of cognitive impairment as measured by the CAMCOG (r(s) = 0.683, p = 0.01) CONCLUSIONS: Patients with vascular dementia had a similar degree of olfactory impairment to those with AD. The UPSIT successfully differentiated between dementia patients and normal elderly British subjects tested in their own homes. The UPSIT did not differentiate between those with AD and vascular dementia.