The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

Systematic review of pre-operative exercise in colorectal cancer patients

The aim of this systematic review was to evaluate the evidence for exercise interventions prior to surgery for colorectal cancer resection. The evidence for use of exercise to improve physical fitness and surgical outcomes is as yet unknown. A systematic search was performed of MEDLINE, EMBASE, CINAHL, AMED and BNI databases for studies involving pre-operative exercise in colorectal cancer patients. Eight studies were included in the review. There is evidence that pre-operative exercise improves functional fitness, and to a lesser extent objectively measurable cardio-respiratory fitness prior to colorectal cancer resection. There is no clear evidence at present that this improvement in fitness translates into reduced peri-operative risk or improved post-operative outcomes. Current studies are limited by risk of bias. This review highlights the common difficulty in transferring promising results in a research setting, into significant improvements in the clinical arena. Future research should focus on which type of exercise is most likely to maximise patient adherence and improvements in cardio-respiratory fitness. Ultimately, adequately powered, randomised controlled trials are needed to investigate whether pre-operative exercise improves post-operative morbidity and mortality

Replacement of soya bean meal with peas and faba beans in growing/finishing pig diets: effect on performance, carcass composition and nutrient excretion

There is now an increasing debate about the viability of using temperate-grown legumes in pig diets as a potential replacement for imported soya bean meal (SBM) and this is due to food security, sustainability and environmental concerns. Two trials were designed to examine nitrogen (N) retention, growth performance and carcass quality of grower and finisher pigs when fed nutritionally balanced SBM-free diets formulated to contain peas or faba beans at 300 g/kg, compared to an SBM-containing, pulse-free control diet. Trial 1 evaluated N digestibility/retention in four iso-energetic diets, comparing the SBM control with one diet formulated with peas and two with faba bean cultivars; a tannin-containing and a tannin-free variety. This trial employed a four by four Latin Square design with four male pigs housed in metabolism crates, fed twice daily at 0.9 of assumed ad libitum intake over four time periods during grower (30–55 kg) and finisher (55–95 kg) phases. Quantitative faecal and urine collection allowed determination of N coefficient of total tract apparent digestibility, coefficient of apparent metabolisability, and N balance. Results revealed that dietary treatment did not affect these N parameters (P > 0.05) during either the grower or finisher phase. Trial 2 evaluated growth performance (feed intake, daily live weight gain and feed conversion ratio) and carcass quality parameters. Five diets (based on SBM, peas and one of three faba bean cultivars) balanced for standard ileal digestible amino acids and net energy were each fed to eight replicates of individually housed entire male pigs over the same growth phases as Trial 1. The inclusion of three faba bean varieties allowed comparison of animal responses between tannin/tannin-free and spring vs. winter bean cultivars. At ∼95 kg, pigs were slaughtered and a comprehensive range of carcass measurements undertaken. Samples of shoulder backfat were also taken at slaughter to determine skatole and indole concentrations. As with N balance, feeding treatment did not affect performance data. Carcass parameters revealed pigs fed with the pea-based diet had a greater dressing percentage than those animals on faba bean-based diets. Pigs fed with the SBM or pea-based diets also had greater lean meat percentages than those on faba-bean diets. Mean skatole concentrations for all pigs were below the accepted maximum threshold level of 0.2 μg/g. In conclusion, it is suggested that peas and faba beans can be successfully fed in balanced pig diets throughout the grower/finisher periods as alternatives to SBM

The Exhibition as an Experiment: An Analogy and its Implications

The analogy of the exhibition as an experiment suggests innovative curatorial approaches that challenge institutional practices. This analogy has however a historical precedence in modernism when itbecame paradigmatic of the exhibitions at the Museum of ModernArt in New York in the 1940s, defining the curatorial approach of its founding director Alfred J Barr. This article considers this early useof the analogy of the exhibition as an experiment and further reflects on its redefinition at the turn of the 20th century by examining how both the notions of the exhibition and of the experiment havechanged over time. In particular, the article examines the different meanings and practices inferred by the concepts of the exhibition and the experiment in the first decades of the 20th century and in the present. It outlines how correspondences between cultural and scientific paradigms can be deployed to tease unacknowledged synergies between two modes of knowledge production (i.e. the art exhibition and the experiment) and address questions of presentness, authority and legitimacy that they imply

Professionalization of a nonstate actor

Can nonstate militants professionalize? That is the core question of this piece. Discussions of professionalism have spread to the state military from civilian professions such as education, medicine, and law. This piece examines whether nonstate actors exhibit the same fundamental processes found within these state-based organizations. These fundamentals are the creation of a recognized internal ethos, which acts as a collective standard for those involved. A commitment to expertise and the punishment of those who do not reach these collective expectations reinforce this ethos. To answer this question, this piece examines the development of the Provisional Irish Republican Army (PIRA) during the Troubles. It highlights consistencies and inconsistencies with traditional forces and argues that groups like the PIRA can professionalize and increase their effectiveness in doing so. This widens the field of professionalism studies and provides an additional lens through which to examine nonstate groups

The association of resilience and physical activity in older adults: cross-sectional analyses from the NICOLA study

Aim: As more of the world’s population are living longer, supporting the mental and physical health of older adults is becoming increasingly important in public health. Resilience is a dynamic process encompassing positive adaptation in the face of adverse experiences that would otherwise lead to poor outcomes. The aim of the study is to explore the association between physical activity and resilience in older adults. Subject and methods: The data used in this study was taken from the results of the Self Completed Questionnaires and Computer Assisted Personal Interviews from the Northern Ireland Cohort for the Longitudinal Study of Ageing. A secondary analysis was conducted on a sample of 4040 participants to examine the association between resilience (Brief Resilience Scale) and on moderate/vigorous physical activity (International Physical Activity Questionnaire – Short Form) through chi-square and Mann–Whitney U tests and an ordinal regression being conducted. Results: Data was included for 4040 participants, of whom 90% did not meet the recommended moderate physical activity guidelines. The findings of this study indicated that higher resilience levels are associated with higher levels of moderate and vigorous physical activity levels. Conclusion: Worryingly, a large percentage of the older adult population are not sufficiently active and this is something that needs to be addressed. The findings suggest that with these low levels of physical activity, interventions should be created to target this population.</p

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

Background: Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods: We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results: Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions: We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli

Neural processes mediating contextual influences on human choice behaviour

Contextual influences on choice are ubiquitous in ecological settings. Current evidence suggests that subjective values are normalized with respect to the distribution of potentially available rewards. However, how this context-sensitivity is realised in the brain remains unknown. To address this, here we examine functional magnetic resonance imaging (fMRI) data during performance of a gambling task where blocks comprise values drawn from one of two different, but partially overlapping, reward distributions or contexts. At the beginning of each block (when information about context is provided), hippocampus is activated and this response is enhanced when contextual influence on choice increases. In addition, response to value in ventral tegmental area/substantia nigra (VTA/SN) shows context-sensitivity, an effect enhanced with an increased contextual influence on choice. Finally, greater response in hippocampus at block start is associated with enhanced context sensitivity in VTA/SN. These findings suggest that context-sensitive choice is driven by a brain circuit involving hippocampus and dopaminergic midbrain

The effects of exercise on pain, fatigue, insomnia, and health perceptions in patients with operable advanced stage rectal cancer prior to surgery: a pilot trial

Background: Promoting quality of life (QoL) is a key priority in cancer care. We investigated the hypothesis that, in comparison to usual care, exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain, fatigue, and insomnia, and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer. Methods: In this non-randomized controlled pilot trial, patients in the supervised exercise group (EG; Mage = 64 years; 64% male) and in the control group (CG; Mage = 72 years; 69% male) completed the European Organization for Research and Treatment of Cancer core Quality of Life questionnaire and the RAND 36-Item Health Survey three times: pre-neoadjuvant chemoradiation therapy (Time 1; nEC = 24; nCG = 11), post-neoadjuvant chemoradiation therapy/pre-exercise intervention (Time 2; nEC = 23; nCG = 10), and post-exercise intervention (Time 3; nEC = 22; nCG = 10). The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training. Patients trained in pairs three times per week for 30 to 40 minutes. Data were analyzed by Mann-Whitney tests and by Wilcoxon matched-pairs signed rank tests. Results: No significant between-group differences in change were found for any of the outcomes. In both groups, fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention. Pain levels also decreased from pre- to post-exercise intervention, albeit not significantly. Conclusions: The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain, fatigue, insomnia, and health perceptions in patients with locally advanced rectal cancer. Trial registration: This study has been registered with clinicaltrials.gov (NCT01325909; March 29, 2011)

How moving home influences appliance ownership: a Passivhaus case study

Low carbon dwellings shift the focus to electricity consumption and appliances by significantly lowering space heating energy consumption. Using a UK Passivhaus (low carbon) case study, interviews and pre/post-move-in appliance audits were employed to investigate how moving home can change the appliance requirements of appliance-using practices. Changes in appliance ownership were due to differences in how appliance-using practices (e.g. cooking, laundering, homemaking) were being performed. Existing/new appliances complemented/conflicted with a new home on the basis of whether the social meanings of specific appliance-using practices (e.g. stylishness, convenience, thermal comfort, cleanliness) could be met. This was evident, when moving home more generally, by households buying new modern appliances and managing spatial constraints. More specifically, regarding Passivhaus, hosting and homemaking practices were performed in ways that met thermal comfort expectations, in addition to appliance purchasing also being influenced by a fear that the Passivhaus technologies could fail. Whilst skills and competences were needed to perform appliance-using practices, these were less prominent in influencing appliance ownership changes. Conclusions include reflections on how the elements of appliance-using practices change when moving home, as well as what adhering to building standards could mean for the standardisation of appliance-using practices and domestic life more generally