Concepts of animal well-being and predicting the impact of procedures on experimental animals

1. We argue that: • in their application to non-human animals, \u27welfare\u27 and \u27well-being\u27 are interchangeable words; and that • good welfare/well-being is the state of being manifest in an animal when its nutritional, environmental, health, behavioural and mental needs are met. 2. These latter are essentially the \u27five freedoms\u27 formulated by the Farm Animal Welfare Council of the United Kingdom. 3. Using the five freedoms as a basis, we have developed a system for assessing the impact of a proposed animal experiment or usage. The freedoms are now transformed into \u27domains of potential compromise\u27 and are redefined better to emphasise the extent of welfare compromise rather than the ideal of absence of compromise. Domain 1 is Thirst/hunger/malnutrition, 2 is Environmental challenge, 3 is Disease/injury/functional impairment, 4 is Behavioural/interactive restriction, and domain 5 is Anxiety/fear/pain/distress. A proposal would be examined systematically in all domains, and the degree of compromise in each rated on a 5-step non-numerical scale - O, A, B, C, X. Anxiety/fear/pain/distress arising from compromise in domains 1-4 would be cumulated into domain 5. The overall rating would commonly be that given to domain 5, but if this were low or unknown, it would be given to the highest rating in the other domains. 4. The proposer would be required to present to the institutional Animal Ethics Committee his/her assessment of the impact of a proposed experiment on the animals involved, together with an appropriate justification for the work and a cost-benefit analysis. 5. The extent of the justification required for a proposal would be directly related to the severity of compromise expected, being low for grade O and very high for grade X. 6. The cost-benefit decision would be based on the balance between the expected severity of welfare compromise and the expected benefits set out in the justification. 7. The major advantage of this system for assessing the impact on welfare is that it encourages systematic consideration of all sources of possible compromise. Such wider consideration would allow more accurate assessment of the severity of impact and thereby would improve the validity and efficiency of cost-benefit analyses. 8. The philosophical background to our approach is outlined, graded examples of welfare compromise are given and ethical and practical implications of using the system are discussed. 9. We also set out what we consider to be the ethical and practical responsibilities of the researcher to the animals, and to his/her assistants. The conscientiousness and comprehensiveness of the assessments of welfare compromise and the actions taken to minimise it are measures of the researcher\u27s acceptance of ethical responsibility for all features of each experiment which affect the animals adversely

Brain natriuretic peptide and NT-proBNP levels reflect pulmonary artery systolic pressure in trekkers at high altitude.

Our objective was to evaluate the utility of the natriuretic peptides BNP (brain natriuretic peptide) and NT-proBNP as markers of pulmonary artery systolic pressure (PASP) in trekkers ascending to high altitude (HA). 20 participants had BNP and NT-proBNP assayed and simultaneous echocardiographic assessment of PASP performed during a trek to 5150 m. PASP increased significantly (p=0.006) with ascent from 24+/-4 to 39+/-11 mm Hg at 5150 m. At 5150 m those with a PASP>/=40 mm Hg (n=8) (versus those with PASP/=400 pg/ml) rise in NT-proBNP at 5150 m (n=4) PASP was significantly higher: 45.9+/-7.5 vs. 32.2+/-6.2 mm Hg (p=0.015). BNP and NT-proBNP may reflect elevated PASP, a central feature of high altitude pulmonary oedema, at HA

Examining the sources of occupational stress in an emergency department

Background Previous work has established that health care staff, in particular emergency department (ED) personnel, experience significant occupational stress but the underlying stressors have not been well quantified. Such data inform interventions that can reduce cases of occupational mental illness, burnout, staff turnover and early retirement associated with cumulative stress. Aims To develop, implement and evaluate a questionnaire examining the origins of occupational stress in the ED. Methods A questionnaire co-designed by an occupational health practitioner and ED management administered to nursing, medical and support staff in the ED of a large English teaching hospital in 2015. The questionnaire assessed participants’ demographic characteristics and perceptions of stress across three dimensions (demand–control–support, effort–reward and organizational justice). Work-related stressors in ED staff were compared with those of an unmatched control group from the acute ear, nose and throat (ENT) and neurology directorate. Results A total of 104 (59%) ED staff returned questionnaires compared to 72 staff (67%) from the acute ENT/neurology directorate. The ED respondents indicated lower levels of job autonomy, management support and involvement in organizational change, but not work demand. High levels of effort–reward imbalance and organizational injustice were reported by both groups. Conclusions Our findings suggest that internal ED interventions to improve workers’ job control, increase support from management and involvement in organizational change may reduce work stress. The high levels of effort–reward imbalance and organizational injustice reported by both groups may indicate that wider interventions beyond the ED are also needed to address these issues

Cosmic Censorship: As Strong As Ever

Spacetimes which have been considered counter-examples to strong cosmic censorship are revisited. We demonstrate the classical instability of the Cauchy horizon inside charged black holes embedded in de Sitter spacetime for all values of the physical parameters. The relevant modes which maintain the instability, in the regime which was previously considered stable, originate as outgoing modes near to the black hole event horizon. This same mechanism is also relevant for the instability of Cauchy horizons in other proposed counter-examples of strong cosmic censorship.Comment: 4 pages RevTeX style, 1 figure included using epsfi

Neutrophil gelatinase-associated lipocalin: its response to hypoxia and association with acute mountain sickness.

Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n = 22) undertaking 6 hours exercise at near sea-level (SL); a cohort (n = 14) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions (n = 52) to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly (P < 0.001) from 68 ± 14 (60-102) at 1300 m to 183 ± 107 (65-519); 143 ± 66 (60-315) and 150 ± 71 (60-357) at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n = 7), mild AMS (n = 16) or no AMS (n = 23): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P = 0.009 for severe versus no AMS; P = 0.026 for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS

Gravitational quasinormal modes for Anti-de Sitter black holes

Quasinormal mode spectra for gravitational perturbations of black holes in four dimensional de Sitter and anti-de Sitter space are investigated. The anti-de Sitter case is relevant to the ADS-CFT correspondence in superstring theory. The ADS-CFT correspondence suggests a prefered set of boundary conditions.Comment: 12 pages, 6 figures in ReVTe

Resistance Noise Scaling in a Dilute Two-Dimensional Hole System in GaAs

We have measured the resistance noise of a two-dimensional (2D)hole system in a high mobility GaAs quantum well, around the 2D metal-insulator transition (MIT) at zero magnetic field. The normalized noise power $S_R/R^2$ increases strongly when the hole density p_s is decreased, increases slightly with temperature (T) at the largest densities, and decreases strongly with T at low p_s. The noise scales with the resistance, $S_R/R^2 \sim R^{2.4}$, as for a second order phase transition such as a percolation transition. The p_s dependence of the conductivity is consistent with a critical behavior for such a transition, near a density p* which is lower than the observed MIT critical density p_c.Comment: 4 pages, 4 figures, to be published in Phys. Rev. Let

The Spread of Bluetongue Virus Serotype 8 in Great Britain and Its Control by Vaccination

Bluetongue (BT) is a viral disease of ruminants transmitted by Culicoides biting midges and has the ability to spread rapidly over large distances. In the summer of 2006, BTV serotype 8 (BTV-8) emerged for the first time in northern Europe, resulting in over 2000 infected farms by the end of the year. The virus subsequently overwintered and has since spread across much of Europe, causing tens of thousands of livestock deaths. In August 2007, BTV-8 reached Great Britain (GB), threatening the large and valuable livestock industry. A voluntary vaccination scheme was launched in GB in May 2008 and, in contrast with elsewhere in Europe, there were no reported cases in GB during 2008.Here, we use carefully parameterised mathematical models to investigate the spread of BTV in GB and its control by vaccination. In the absence of vaccination, the model predicted severe outbreaks of BTV, particularly for warmer temperatures. Vaccination was predicted to reduce the severity of epidemics, with the greatest reduction achieved for high levels (95%) of vaccine uptake. However, even at this level of uptake the model predicted some spread of BTV. The sensitivity of the predictions to vaccination parameters (time to full protection in cattle, vaccine efficacy), the shape of the transmission kernel and temperature dependence in the transmission of BTV between farms was assessed.A combination of lower temperatures and high levels of vaccine uptake (>80%) in the previously-affected areas are likely to be the major contributing factors in the control achieved in England in 2008. However, low levels of vaccination against BTV-8 or the introduction of other serotypes could result in further, potentially severe outbreaks in future

Birthweight, HIV exposure and infant feeding as predictors of malnutrition in Botswanan infants

Background: A better understanding of the nutritional status of infants who are HIV-Exposed-Uninfected (HEU) and HIV-Unexposed-Uninfected (HUU) during their first 1000 days is key to improving population health, particularly in sub-Saharan Africa. Methods: A cross-sectional study compared the nutritional status, feeding practices and determinants of nutritional status of HEU and HUU infants residing in representative selected districts in Botswana during their first 1000 days of life. Four hundred and thirteen infants (37.3% HIV-exposed), aged 6–24 months, attending routine child health clinics, were recruited. Anthropometric, 24-h dietary intake and socio-demographic data was collected. Anthropometric Z-scores were calculated using 2006 World Health Organization growth standards. Modelling of the determinants of malnutrition was undertaken using logistic regression. Results: Overall, the prevalences of stunting, wasting and being underweight were 10.4%, 11.9% and 10.2%, respectively. HEU infants were more likely to be underweight (15.6% versus 6.9%), (P &lt; 0.01) and stunted (15.6% versus 7.3%), (P &lt; 0.05) but not wasted (P = 0.14) than HUU infants. HEU infants tended to be formula fed (82.5%), whereas HUU infants tended to breastfeed (94%) for the first 6 months (P &lt; 0.001). Significant predictors of nutritional status were HIV exposure, birthweight, birth length, APGAR (appearance, pulse, grimace, activity and respiration) score and mother/caregiver's education with little influence of socio-economic status. Conclusions: HEU infants aged 6–24 months had worse nutritional status compared to HUU infants. Low birthweight was the main predictor of undernutrition in this population. Optimisation of infant nutritional status should focus on improving birthweight. In addition, specific interventions should target HEU infants aiming to eliminate growth disparity between HEU and HUU infants.</p

Real-space imaging of quantum Hall effect edge strips

We use dynamic scanning capacitance microscopy (DSCM) to image compressible and incompressible strips at the edge of a Hall bar in a two-dimensional electron gas (2DEG) in the quantum Hall effect (QHE) regime. This method gives access to the complex local conductance, Gts, between a sharp metallic tip scanned across the sample surface and ground, comprising the complex sample conductance. Near integer filling factors we observe a bright stripe along the sample edge in the imaginary part of Gts. The simultaneously recorded real part exhibits a sharp peak at the boundary between the sample interior and the stripe observed in the imaginary part. The features are periodic in the inverse magnetic field and consistent with compressible and incompressible strips forming at the sample edge. For currents larger than the critical current of the QHE break-down the stripes vanish sharply and a homogeneous signal is recovered, similar to zero magnetic field. Our experiments directly illustrate the formation and a variety of properties of the conceptually important QHE edge states at the physical edge of a 2DEG.Comment: 7 page