PAlliative Care in chronic Kidney diSease: the PACKS study—quality of life, decision making, costs and impact on carers in people managed without dialysis

BACKGROUND: The number of patients with advanced chronic kidney disease opting for conservative management rather than dialysis is unknown but likely to be growing as increasingly frail patients with advanced renal disease present to renal services. Conservative kidney management includes ongoing medical input and support from a multidisciplinary team. There is limited evidence concerning patient and carer experience of this choice. This study will explore quality of life, symptoms, cognition, frailty, performance decision making, costs and impact on carers in people with advanced chronic kidney disease managed without dialysis and is funded by the National Institute of Health Research in the UK.

METHODS: In this prospective, multicentre, longitudinal study, patients will be recruited in the UK, by renal research nurses, once they have made the decision not to embark on dialysis. Carers will be asked to 'opt-in' with consent from patients. The approach includes longitudinal quantitative surveys of quality of life, symptoms, decision making and costs for patients and quality of life and costs for carers, with questionnaires administered quarterly over 12 months. Additionally, the decision making process will be explored via qualitative interviews with renal physicians/clinical nurse specialists.

DISCUSSION: The study is designed to capture patient and carer profiles when conservative kidney management is implemented, and understand trajectories of care-receiving and care-giving with the aim of optimising palliative care for this population. It will explore the interactions that lead to clinical care decisions and the impact of these decisions on informal carers with the intention of improving clinical outcomes for patients and the experiences of care givers.

The role of WNT singling activation and its blockage in the focal retinal lesion of Ccl2-/-/Cx3cr1-/- mice with and without rd8 background

Purpose: The canonical Wnt signaling is activated by retinal injury. Under disease conditions, the Wnt mediates inflammatory responses. Inflammation has been detected in age-related macular degeneration (AMD) retinas and Ccl2-/-/Cx3cr1-/- (DKO) mice with or without rd8 background, a model with progressive AMD-like lesions including focal photoreceptor/RPE degeneration and A2E accumulation. We evaluated the effects of Wnt-β-catenin activation and an antibody against LRP6, the co-receptor of Wnt on these two models.

Methods: anti-LRP6 antibody (2F1, 1 μl of 5 μg/μL) was intravitreally injected into the right eyes in 3 separate experiments (DKOrd8, N=35; DKO, N=10). The left eyes were injected with mouse IgG as controls. Fundoscopy was taken before injection and sequentially monthly after injection. Two months after injection, light-adapted ERG responses were recorded; then the eyes were harvested for histopathology, the determination of retinal A2E, and molecular analysis. The microarray of ocular mRNA of 92 Wnt genes was compared between the treated and the control eyes. The phosphorylated types of LRP6 and β-catenin and endogenous forms of the proteins were assayed by Western blotting.

Results: For DKOrd8 mice, the fundus showed a slower progression or alleviation of retinal lesions in the right eyes as compared to the left eyes. Among 35 pairs of eyes, 26 (74.3%) were improved, 7 (20%) stayed the same and 2 (5.7%) remained progressing. Histology confirmed the clinical observation. Light-adapted ERG of the treated eyes exhibited larger amplitudes compared to control eyes (n=6), with greater improvements under UV light stimulus. There was a significantly lower A2E in the treated eyes compared to controls. Microarray of 92 Wnt genes expression pattern was similar in both eyes. Western blotting indicated local administration of 2F1 antibody to suppress the activation of Wnt pathway in the retina. For DKO mice, the treatment improved ERG but less effect on RPE degeneration.

Conclusions: The canonical Wnt signaling plays a role in the focal retina lesion of both DKOrd8 and DKO mice; and intravitreal anti-LRP6 antibody might be neuroprotective via deactivation of canonical Wnt pathway.

Injurious tail biting in pigs: How can it be controlled in existing systems without tail docking?

Tail biting is a serious animal welfare and economic problem in pig production. Tail docking, which reduces but does not eliminate tail biting, remains widespread. However, in the EU tail docking may not be used routinely, and some 'alternative' forms of pig production and certain countries do not allow tail docking at all. Against this background, using a novel approach focusing on research where tail injuries were quantified, we review the measures that can be used to control tail biting in pigs without tail docking. Using this strict criterion, there was good evidence that manipulable substrates and feeder space affect damaging tail biting. Only epidemiological evidence was available for effects of temperature and season, and the effect of stocking density was unclear. Studies suggest that group size has little effect, and the effects of nutrition, disease and breed require further investigation. The review identifies a number of knowledge gaps and promising avenues for future research into prevention and mitigation. We illustrate the diversity of hypotheses concerning how different proposed risk factors might increase tail biting through their effect on each other or on the proposed underlying processes of tail biting. A quantitative comparison of the efficacy of different methods of provision of manipulable materials, and a review of current practices in countries and assurance schemes where tail docking is banned, both suggest that daily provision of small quantities of destructible, manipulable natural materials can be of considerable benefit. Further comparative research is needed into materials, such as ropes, which are compatible with slatted floors. Also, materials which double as fuel for anaerobic digesters could be utilised. As well as optimising housing and management to reduce risk, it is important to detect and treat tail biting as soon as it occurs. Early warning signs before the first bloody tails appear, such as pigs holding their tails tucked under, could in future be automatically detected using precision livestock farming methods enabling earlier reaction and prevention of tail damage. However, there is a lack of scientific studies on how best to respond to outbreaks: the effectiveness of, for example, removing biters and/or bitten pigs, increasing enrichment, or applying substances to tails should be investigated. Finally, some breeding companies are exploring options for reducing the genetic propensity to tail bite. If these various approaches to reduce tail biting are implemented we propose that the need for tail docking will be reduced. © 2014 The Animal Consortium.

Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)

Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".

Strength of visual percept generated by famous faces perceived without awareness: effects of affective valence, response latency, and visual field

Participants who were unable to detect familiarity from masked 17 ms faces ([Stone and Valentine, 2004] and [Stone and Valentine, in press-b]) did report a vague, partial visual percept. Two experiments investigated the relative strength of the visual percept generated by famous and unfamiliar faces, using masked 17 ms exposure. Each trial presented simultaneously a famous and an unfamiliar face, one face in LVF and the other in RVF. In one task, participants responded according to which of the faces generated the stronger visual percept, and in the other task, they attempted an explicit familiarity decision. The relative strength of the visual percept of the famous face compared to the unfamiliar face was moderated by response latency and participants’ attitude towards the famous person. There was also an interaction of visual field with response latency, suggesting that the right hemisphere can generate a visual percept differentiating famous from unfamiliar faces more rapidly than the left hemisphere. Participants were at chance in the explicit familiarity decision, confirming the absence of awareness of facial familiarity.

Hygrothermal performance of wood-hemp insulation in timber frame wall panels with and without a vapour barrier

An in situ experiment on a full-scale timber frame test building was carried out to study the hygrothermal performance of wood-hemp composite insulation in timber frame wall panels with and without a vapour barrier. The heat transfer properties and the likelihood of mould growth and condensation in the panels were compared. Step changes in the internal relative humidity were performed to explore the effects of high, normal and low internal moisture loads on the wall panels. No significant difference in the average equivalent thermal transmittance (U-values) between the panels with and without a vapour barrier was observed. The average equivalent U-values of the panels were close to the U-values calculated from the manufacturers’ declared thermal conductivity values of the insulation. The likelihood of condensation was higher at the interface of the wood-hemp insulation and the oriented strand board (OSB) in the panel without a vapour barrier. In terms of the parametric assessment of the mould germination potential, the relative humidity, the temperature and the exposure conditions in the insulation-OSB interfaces of the panel without a vapour barrier were found to be more favourable to the germination of mould spores. Nonetheless, when the insulations were dismantled, no mould was visually detected.

The world without outside

The world is all that there is. In the world, ontology and epistemology coincide. The thing and the perspective are part of it, scale is ingested in its multiplicity, communication stops at the world's edge. By reading together Deleuze and Guattari's plane of immanence and Niklas Luhmann's proto-global concept of Weltgesellschaft (“world society”), I suggest a conceptualisation of the world as the materiality of the multiple spaces of creation in an insular, all-inclusive immanence. Deprived of an outside, the world pushes its own understanding of circumference through, first, the expansion of its own limits through the process of worlding, and, second, the multiplication of modes of material (self-)production through its process of othering. Thus, the world swells up from the inside and expands on both the material and the semantic level, producing a multiplicity of fractal microcosms. Issues of responsibility and justice arise that are intricately linked to the materiality of the world and take place in and between the various bodies and spaces of the world but without an overarching hierarchy or principle. This approach is a way of counteracting the all-pervasive Hegelian understanding of synthesis, arguing instead for a plenitude that brims with positivity and that can never become fully complete. The world remains its own infinite process of worlding.

Tackling the terrorists: the experience of internment without trial in Northern Ireland

In August 1971, the devolved Stormont administration in Northern Ireland introduced internment without trial of those suspected of involvement in IRA terrorism. Ever since, the policy has been regarded as an abject failure. This article will reassess many of the key questions about internment: why did the Northern Ireland government introduce it when it did? Why did the Westminster government agree to a measure without parallel in British peacetime history? Why did it fail, when it had worked before? Was internment always doomed, or only because it was badly implemented? What was the alternative? How does the liberal democratic state defend itself against violent subversion without itself resorting to brutality and violence? This article is based on archival research in Great Britain, Northern Ireland and the Republic of Ireland, and on interviews with former internees, politicians and civil servants, and former members of the security forces. It suggests that internment was a relatively humane and honest policy and might, in different circumstances, have spared Northern Ireland thirty years of murder and mayhem.