Introduction to a comparative study of the right to freedom of thought

This is the introduction for the special issue on a comparative study of the right to freedom of thought across several jurisdictions including the UK, Ireland, Canada and the USA as well as the regional jurisdictions of the European Court of Human Rights and the Inter-American Court of Human Rights

A model of spatially evolving herpesvirus epidemics causing mass mortality in Australian pilchard Sardinops sagax

In 1995 mass mortality of pilchards Sardinops sagax occurred along >5000 km of Australian coast; similar events occurred in 1998/99. This mortality was closely associated with a herpesvirus. The pilchard is an important food source for larger animals and supports commercial fisheries. Both epidemics originated in South Australian waters and spread as waves with velocities of 10 to 40 km d-1. Velocity was constant for a single wave, but varied between the epidemics and between the east- and west-bound waves in each epidemic. The pattern of mortality evolved from recurrent episodes to a single peak with distance from the origin. A 1-dimensional model of these epidemics has been developed. The host population is divided into susceptible, infected and latent, infected and infectious, and removed (recovered and dead) phases; the latent and infectious periods are of fixed duration. This model produces the mortality patterns observed locally and during the spread and evolution of the epidemic. It is consistent with evidence from pathology. The wave velocity is sensitive to diffusion coefficients, viral transmission rates and latent period. These parameters are constrained using the local and large-scale patterns of epidemic spread. The relative roles of these parameters in explaining differences between epidemics and between east- and west-bound waves within epidemics are discussed. The model predicts very high levels of infection, indicating that many surviving pilchards recovered following infection. Control appears impracticable once epidemics are initiated, but impact can be minimised by protecting juvenile stocks

Protocol for a randomised control trial of methylnaltrexone for the treatment of opioid-induced constipation and gastrointestinal stasis in intensive care patients (MOTION)

Gastrointestinal dysmotility and constipation are common problems in intensive care patients. The majority of critical care patients are sedated with opioids to facilitate tolerance of endotracheal tubes and mechanical ventilation, which inhibit gastrointestinal motility and lead to adverse outcomes. Methylnaltrexone is a peripheral opioid antagonist that does not cross the blood-brain barrier and can reverse the peripheral side effects of opioids without affecting the desired central properties. This trial will investigate whether methylnaltrexone can reverse opioid-induced constipation and gastrointestinal dysmotility.This is a single-centre, multisite, double-blind, randomised, placebo-controlled trial. 84 patients will be recruited from 4 intensive care units (ICUs) within Imperial College Healthcare NHS Trust. Patients will receive intravenous methylnaltrexone or placebo on a daily basis if they are receiving opioid infusion to facilitate mechanical ventilation and have not opened their bowels for 48 hours. All patients will receive standard laxatives as per the clinical ICU bowel protocol prior to randomisation. The primary outcome of the trial will be time to significant rescue-free laxation following randomisation. Secondary outcomes will include tolerance of enteral feed, gastric residual volumes, incidence of pneumonia, blood stream and Clostridium difficile infection, and any reversal of central opioid effects.The trial protocol, the patient/legal representative information sheets and consent forms have been reviewed and approved by the Harrow Research Ethics Committee (REC Reference 14/LO/2004). An independent Trial Steering Committee and Data Monitoring Committee are in place, with patient representation. On completion, the trial results will be published in peer-reviewed journals and presented at national and international scientific meetings.2014-004687-37; Pre-results

Differences in the epidemiology of theileriosis on smallholder dairy farms in contrasting agro-ecological and grazing strata of highland Kenya

A prospective cohort study was conducted in five purposively-sampled agro-ecological zone (AEZ)-grazing system strata in Murang’a District, Kenya, between March 1995 and June 1996. The study strata were selected based on a preliminary characterization study to represent the widest range of risks to East Coast fever (ECF) in the District and included zero-grazing and open-grazing farms. In total, 225 calves from 188 smallholder farms were examined from birth to 6 months of age and visited within the first 2 weeks of life and thereafter at bi-weekly intervals for up to 14 visits. The purpose of the study was to characterize the differences in epidemiology (risks of infection, morbidity and mortality) and potential control of ECF between the selected strata. Evidence of Theileria parva infection was assessed by increased antibody levels as measured in an indirect ELISA assay by the percent positivity (PP) of serum samples relative to a strong positive reference serum. Sero-conversion risks of T. parva were highest in the open-grazing strata. Antibody prevalence in adult cattle and ECF morbidity and mortality risks were also highest in open-grazing strata. While different, all five AEZ-grazing strata were considered to be endemically unstable for ECF. East Coast fever challenge was low in all zero-grazing strata and this challenge is likely to remain low due to continuing intensification of smallholder farming in the central highlands. In the open-grazing strata, there was higher challenge and a greater impact of ECF. ILRI publication no.: 99017

The Canine POMC Gene, Obesity in Labrador Retrievers and Susceptibility to Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) in dogs is a common endocrinopathy with a complex genetic architecture. Disease susceptibility in several breeds is associated with polymorphisms in immune response genes, but in the Labrador retriever breed, no genetic associations with DM have been identified. A deletion in the pro-opiomelanocortin (POMC) gene in Labrador retrievers is associated with increased appetite and risk of obesity. HYPOTHESIS/OBJECTIVES: To characterize the POMC deletion in Labrador retrievers, to develop a simple genetic test for this mutation, and to test the hypothesis that the POMC gene deletion is associated with an increased risk of DM in this breed. ANIMALS: Sixty-one non-diabetic Labrador retrievers aged >6 years and 57 Labrador retrievers with DM. METHODS: Case-control genotyping study to compare the frequency of the POMC deletion in dogs with and without DM. After polymerase chain reaction (PCR) and sequencing to characterize the mutation, a PCR-based test was developed and validated using 2 different restriction fragment length polymorphism assays. RESULTS: A 14-base-pair deletion was confirmed and localized to exon 3 of the canine POMC gene. A PCR-based test for the deletion was successfully developed. There was no association between the presence of the POMC deletion mutation and DM in this population of Labrador retriever dogs (P = .31). CONCLUSIONS AND CLINICAL IMPORTANCE: This study adds to the existing scientific literature indicating that there is little evidence for a direct link between obesity and DM in dogs

Improved Food Safety through Sterility of Air in Food Processing and Packaging.

End of Project ReportThe aims of this research were to develop reliable methods for evaluating the level of airborne micro-organisms in food processing facilities and to study the viability and behaviour of micro-organisms in air filtration systems. The main conclusions were as follows: · Assessment of air quality involves monitoring both particulate and microbial levels as there is no simple relationship between these phenomena in a food process environment. · The large fluctuations in microbial levels found in air in these studies underline the necessity of frequent and regular air sampling in processing facilities. · It was established that micro-organisms can grow inside an air filter under certain environmental conditions and give rise to intermittent microbial germ contamination of the cleaned air. · It was demonstrated that flowing air affects the survival of microorganisms and the survival rate is dependent on filter class. Hence more emphasis on filter design aimed at effective microbial control is advised. · A combined system for filtering and sterilisation by ozone was demonstrated to be an efficient technique for extending the microbial separation efficiency of air filters.European Unio

Ratcheting Heat Flux against a Thermal Bias

Merely rocking the temperature in one heat bath can direct a steady heat flux from cold to hot against a non-zero thermal bias in stylized nonlinear lattice junctions that are sandwiched between two heat baths. Likewise, for an average zero-temperature difference between the two contacts a net, ratchet-like heat flux emerges. Computer simulations show that this very heat flux can be controlled and reversed by suitably tailoring the frequency ($\lesssim$ 100 MHz) of the alternating temperature field.Comment: 5 pages, 6 figure

Impaired awareness of action-outcome contingency and causality during healthy ageing and following ventromedial prefrontal cortex lesions

Detecting causal relationships between actions and their outcomes is fundamental to guiding goal-directed behaviour. The ventromedial prefrontal cortex (vmPFC) has been extensively implicated in computing these environmental contingencies, via animal lesion models and human neuroimaging. However, whether the vmPFC is critical for contingency learning, and whether it can occur without subjective awareness of those contingencies, has not been established. To address this, we measured response adaption to contingency and subjective awareness of action-outcome relationships in individuals with vmPFC lesions and healthy elderly subjects. We showed that in both vmPFC damage and ageing, successful behavioural adaptation to variations in action-outcome contingencies was maintained, but subjective awareness of these contingencies was reduced. These results highlight two contexts where performance and awareness have been dissociated, and show that learning response-outcome contingencies to guide behaviour can occur without subjective awareness. Preserved responding in the vmPFC group suggests that this region is not critical for computing action-outcome contingencies to guide behaviour. In contrast, our findings highlight a critical role for the vmPFC in supporting awareness, or metacognitive ability, during learning. We further advance the hypothesis that responding to changing environmental contingencies, whilst simultaneously maintaining conscious awareness of those statistical regularities, is a form of dual-tasking that is impaired in ageing due to reduced prefrontal function.Recruitment and characterisation of individuals with brain lesions was made possible by the Cambridge Cognitive Neuroscience Research Panel at the MRC Cognition and Brain Sciences Unit, Cambridge. We acknowledge the contribution of Dr Sharon Erzinçlioğlu, Prof. Facundo Manes and Dr Tilak Das (consultant radiologist, Addenbroke’s Hospital) for their involvement in co-ordinating the panel, lesion tracing, and referral to the panel. This research was funded by a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) to TWR. Work was completed at the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK, supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). CO is supported by a National Health and Medical Research Council Neil Hamilton Fairley Fellowship (GNT 1091310). MMV is supported by a Pinsent Darwin Scholarship in Mental Pathology and Angharad Dodds John Bursary in Mental Health and Neuropsychiatry

Navigated functional alignment total knee arthroplasty achieves reliable, reproducible and accurate results with high patient satisfaction

Purpose: The decision on which technique to perform a total knee arthroplasty (TKA) has become more complicated over the last decade. Perceived limitations of mechanical alignment (MA) and kinematic alignment (KA) have led to the development of the functional alignment (FA) philosophy. This study aims to report the 2-year results of an initial patient cohort in terms of revision rate, PROMs and complications for Computer Aided Surgery (CAS) Navigated FA TKA. Methods: This paper reports a single surgeon’s outcomes of 165 consecutive CAS FA TKAs. The final follow-up was 24 months. Pre-operative and post-operative patient-reported outcome measures, WOMAC and KSS, and intra-operative CAS data, including alignment, kinematic curves, and gaps, are reported. Stress kinematic curves were analysed for correlation with CAS final alignment and CAS final alignment with radiographic long-leg alignment. Pre- and post-operative CPAK and knee phenotypes were recorded. Three different types of prostheses from two manufacturers were used, and outcomes were compared. Soft tissue releases, revision and complication data are also reported. Results: Mean pre-operative WOMAC was 48.8 and 1.2 at the time of the final follow-up. KSS was 48.8 and 93.7, respectively. Pre- and post-operative range of motion was 118.6° and 120.1°, respectively. Pre-operative and final kinematic curve prediction had an accuracy of 91.8%. CAS data pre-operative stress alignment and final alignment strongly correlate in extension and flexion, r = 0.926 and 0.856, p < 0.001. No statistical outcome difference was detected between the types of prostheses. 14.5% of patients required soft tissue release, with the lateral release (50%) and posterior capsule (29%) being the most common. Conclusion: CAS FA TKA in this cohort proved to be a predictable, reliable, and reproducible technique with acceptable short-term revision rates and high PROMs. FA can account for extremes in individual patient bony morphology and achieve desired gap and kinematic targets with soft tissue releases required in only 14.5% of patients. Level of evidence: IV (retrospective case series review)

Improving the Quality of European Hard Cheese by controlling interactions between Lactic Acid Bacteria and Propionic Acid Bacteria (LAB/PAB) (Stimulation of Propionic Acid Bacteria by Lactic

End of Project ReportTeagasc acknowledges with gratitude grant aid under the EU Framework Programme (FAIR 96-CT-1024).In the manufacture of Swiss-type cheese two successive fermentations occur. During manufacture, lactic acid bacteria (LAB), particularly Streptococcus thermophilus, Lactobacillus helveticus and Lb. delbrueckii subsp. lactis, convert lactose to lactate while, during ripening, propionic acid bacteria (PAB) convert lactate to propionic acid, acetic acid and carbon dioxide (CO2). CO2 is responsible for eye formation and propionic acid results in the typical nutty flavour of Swiss-type cheese. There have been a few reports of interactions between a small number of LAB and PAB but the compounds involved have not been identified. A better understanding of this phenomenon is necessary to select strains of PAB for cheesemaking and improve the quality of hard cheeses. Cheese cannot be used for such a study because of its complexity and the length of time it is ripened. Hence, a simple whey-based model developed by Piveteau et al (1995) was successfully used to study the interactions between LAB and PAB. In this procedure, the LAB were grown overnight in milk and the whey was collected by centrifugation. After neutralisation and filter-sterilisation, the growth of strains of PAB in this whey and in a control whey produced from the same milk by acidification with lactic acid were compared. The objectives of this study were to refine the model of Piveteau et al (1995) to study the interactions between LAB and PAB and to determine the nature of the stimulant(s) produced by the LAB. * Thirty-two combinations of different commercial strains of PAB and LAB were evaluated in a modified whey model. None showed any inhibition and all showed some degree of stimulation but the extent of the stimulation depended on the particular pair of PAB and LAB used. * An inhibitor of PAB was found in milk, which prevented the growth of PAB from low (105 cfu/ml) but not from high inocula (107 cfu/ml). The inhibitor was heat stable (to autoclaving for 15 min), of low molecular mass and could be removed by pre-growth of some but not all starter LAB in milk. * Growth of P. freudenreichii DPC 3801 in control whey was stimulated by peptone, tryptone, casein hydrolysed by the crude proteinase of Lb. helveticus DPC 4571 and by pre-growth of the lactobacillus in milk, but not by vitamins (riboflavin, thiamine, PABA, Ca panthothenate, biotin and nicotinic acid) or minerals (MgSO4, MnCl2, CoCl2 and CuSO4). * Growth of Lb. helveticus DPC 4571 in milk resulted in significant increases in peptide and amino acid production but the amino acids produced did not stimulate the growth of the PAB. Based on these results it was concluded that the stimulation was due to production of peptides by the LAB from casein. * The whey model developed by Piveteau et al (1995) to study the interactions between PAB and LAB was shown to be reproducible. Adjustment of the pH of the whey to 5.4 rather than 6.0, incubation at 24ºC rather than 30ºC and addition of 1% NaCl, to simulate cheese ripening conditions allowed growth of all the PAB tested. * Several chromatographic procedures, including ion-exchange, gel permeation and reverse-phase, high-pressure liquid chromatography failed to categorically identify the peptide(s) responsible for the stimulation of the PAB. In some of these chromatographic systems,the stimulatory activity was shown to be present in several peaks implying that different peptides were involved.European Unio