Aetiology of systemic inflammation and its link with prognosis in gastro-oesophageal cancer

INTRODUCTION: As the incidence of gastro-oesophageal cancer continues to increase accurate staging remains challenging and the general outlook for these patients is poor. As well as improving prognostic accuracy, investigation of systemic inflammation and cachexia in these patients may enable the identification of much needed novel therapeutic targets.AIMS: The aims of this thesis were to describe the genesis, mediators and clinical sequelae of systemic inflammation in patients with gastro -oesophageal cancer. The usefulness of systemic inflammation as a prognostic indicator and the role of cachexia as a factor in the adverse prognosis associated with systemic inflammation were expanded in detail. The key hypothesis being that tumour cells produce mediators (eg cytokines), which can either directly or indirectly (via systemic inflammation) induce a catabolic state in the peripheral tissues of the host. Such wasting may be one of the mechanisms linking systemic inflammation with adverse prognosis in patients with cancer.MATERIALS & METHODS: A consecutive series of 220 patients with gastric or oesophageal cancer were studied. Data were collected prospectively and a nutritional assessment and performance status were determined for each patient and survival duration was recorded. Samples of blood, urine and tumour tissue were collected for determination of cytokine and acute phase protein concentrations. The expression of other potential tumour -derived mediators, parathyroid hormone -related peptide (PTHrP) and proteolysis- inducing factor (PIF), were also studied.RESULTS: Systemic inflammation (CRP >10 mg /I) was present in 43% of patients with gastrooesophageal cancer. Serum acute phase protein concentrations (especially CRP), but not serum cytokine concentrations, were robust measures of systemic inflammatory activity. However, concentrations of pro -inflammatory cytokines within tumour tissue were significantly elevated and were linked with markers of systemic inflammation. IL-18 in particular was over - expressed in tumour tissue and may be a key determinant of systemic inflammation in patients with gastro -oesophageal malignancy. A chronic inflammatory cell infiltrate into the tumour tissue was present in 75% of tumours and was also linked with markers of systemic inflammation. Tumour cells or host immune cells or a combination of the two may be the main source of these mediators. The presence of systemic inflammation was also influenced by host cytokine genotype. Other potential tumour -derived mediators, such as PIF and PTHrP, may also play a (minor) role in the generation of systemic inflammation. These factors may also have additional effects on the host, such as potentiating weight loss. CRP concentrations were identified as the best marker of prognosis and the magnitude of serum CRP concentrations were negatively linked with survival duration.83% of patients had lost weight at the time of diagnosis and within 3 months this had increased to 92 %. Increasing weight loss was positively associated with serum markers of systemic inflammation. Weight loss among patients with gastro -oesophageal cancer was not accounted for entirely by reduced food intake or mechanical obstruction secondary to the tumour. Alternatively, the presence of systemic inflammation contributed to nutritional decline (estimate of effect 34 %). Weight loss was associated with adverse outcome and cachexia may be an aetiological factor involved in the link between systemic inflammation and adverse prognosis.CONCLUSIONS: Systemic inflammation, weight loss, performance status, and stage of disease were the main determinants of outcome in patients with gastro-oesophageal cancer. These factors were used to devise a novel model to improve prognostic accuracy to aid clinical decision-making for these patients. These studies identify systemic inflammation as both an important prognostic indicator and a potential therapeutic target for patients with gastro-oesophageal malignancy

FANCL (FA complementation group L)

Review on FANCL, with data on DNA, on the protein encoded, and where the gene is implicated

The effect of dispersal behavior on stability in populations, communities, and ecosystems

Habitat choice, when organisms move among habitat patches in a directed fashion based on environmental cues, is an underappreciated force in Ecology. Theoretical work suggests that such choice behavior might be a potent source of stability in populations, communities, and ecosystems. I tested the effects of dispersal behavior on stability with a series of mesocosm experiments at each of these scales. In populations of snails with stochastic disturbance, I found that movement among patches was density-dependent: snails tended to move away from high density and toward low density. These movements had dampening effect on oscillations in abundance, and they contributed to longer population persistence times relative to populations that were not connected by dispersal. A second experiment manipulated the colonization behavior of aquatic insects in order to see how this dispersal behavior affects the community response to a pulse of fish predation on the insect communities. While choice behavior exacerbated the effects of fish predation, reducing species richness beyond what was observed in communities with randomized colonization, choice resulted in faster recovery of communities relative to random colonization. A third experiment explored the effects of pulses of nutrient additions in mesocosms with developing aquatic insect communities. Presence of sediment had weak effects on stability, with small pulses of nutrients supporting more stable abundance values than ecosystems with no sediment. This stabilization effect was likely driven by habitat choice behavior, since the sediment input treatments affected organisms with active dispersal more than those with passive dispersal. Collectively, these experiments show that dispersal behavior is an important factor to consider when attempting to explain the spatial and temporal variation in ecosystems. Habitat choice behavior can have particularly significant effects on stability. Predicting how species respond to environmental change therefore requires knowledge of how they move.Ecology, Evolution and Behavio

Diversity and complexity of arthropod references in haiku.

Haiku are short poems, each composed of about 10 words, that typically describe moments in nature. People have written haiku since at least the 17th century, and the medium continues to be popular with poets, amateurs, educators, and students. Collectively, these poems represent an opportunity to understand which aspects of nature-e.g., which taxa and biological traits-resonate with humans and whether there are temporal trends in their representation or the emotions associated with these moments. We tested this potential using a mix of linguistic and biological methods, in analyses of nearly 4,000 haiku that reference arthropods. We documented the taxa and the life history traits represented in these poems and how they changed over time. We also analyzed the poems for emotion and tone. Our results reveal a mix of predictable trends and compelling surprises, each of which stand to potentially inform engagement strategies. At least 99 families of arthropods, in 28 orders, are represented in these haiku. The eight most commonly referenced taxa, from highest to lowest number of references, include: Lepidoptera, Hymenoptera, Diptera, Coleoptera, Araneae, Orthoptera, Hemiptera, and Odonata. Several common, conspicuous orders were never referenced, including Trichoptera, Plecoptera, and Megaloptera. The most commonly referenced traits relate to ecology (especially habitat, phenology, time of day), behavior (especially sound production), phenotype (especially color), and locomotion (especially flight). The least common traits in haiku relate to arthropod reproduction and physiology. Our analyses revealed few obvious temporal trends in the representations of taxa, biological traits, or emotion and tone. The broader implications of these results and possible future directions are discussed

What’s dignity got to do with it? Patient experience of the dignity care intervention: a qualitative evaluation study

The delivery of palliative care in the community setting has been recognized as a valued and challenging aspect of nursing care. To this end, care pathways have been shown to support nurses in a variety of settings to deliver individualized patient care. This study provides a qualitative evaluation of an end-of-life intervention known as the Dignity Care Intervention (DCI) based on patients’ perspectives. The DCI consists of four sections: a manual, the Patient Dignity Inventory, reflective questions, and evidence-based care actions. A qualitative design underpinned by the philosophy of Merlau-Ponty was employed for the evaluation of the DCI. Data collection included individual interviews with participants (n = 25). Interview data were analyzed using framework thematic analysis. Four theme categories were identified: “experience of DCI,” “responding to my illness concerns,” “how illness affects me as a person,” and “how illness concerns affect my relationships.” The DCI was found to enable patients to discuss openly important issues with community nurses that they might not otherwise have raised. Participants conveyed satisfaction with the support they received through the DCI. The use of care pathways detailing interventions to manage clinical problems and ensure systematic integration of the best available evidence into care delivery can improve end-of-life care

Measurement of tissue cortisol levels in patients with severe burns: a preliminary investigation

Introduction The assessment of adrenal function in critically ill patients is problematic, and there is evidence to suggest that measurement of tissue glucocorticoid activity may be more useful than estimation of plasma cortisol concentrations. Interstitial cortisol concentrations of cortisol represent the available pool of glucocorticoids able to enter the cell and bind to the glucocorticoid receptor. However the concentrations of plasma cortisol may not accurately reflect interstitial concentrations. We elected to perform a preliminary study into the feasibility of measuring interstitial cortisol by microdialysis, and to investigate the relationship between total plasma cortisol, free plasma cortisol and interstitial cortisol in patients with severe burns

Interrater reliability of directly-observed stepping and reclining in lower limb amputees in a laboratory setting

Introduction: Accurate measurement of physical behaviours in adults with lower limb absence is essential to report true patterns of physical behaviour and the effectiveness of interventions. Observation methods are often used for criterion-related validation. Establishing interrater reliability within direct observation methods is an important and necessary precursor to criterion-related validitystudies. Purpose: To assess the interrater reliability for quantifying steps and reclining time in simulated lifestyle activities in adults with unilateral lower limb absence. Methods: 15 adults completed three trials of a simulated set of lifestyle activities including kitchen work, sitting and lying and purposefulwalking. Trials were video recorded and subsequently analysed independently by three trained raters for three types of behavioural event (incidental stepping, purposeful stepping and reclining). Data were analysed using oneway intraclass correlation coefficients (ICC) and oneway repeated measures ANOVAand effect sizes (Cohen's d). Results: Reliability was high for the reliability of three raters (ICCs ranged from .98-1.00 for the three types of physical behaviours), and also when adjusted for a single rater (ICCsranged from .93-.99). Although there were significant (p < .05) mean differences among raters for incidental steps, total steps, and reclining time, these corresponded to small effect sizes (d = 0.08-0.29).Conclusions: Trained raters are able to consistently judge brief, incidental stepping and more prolonged stepping events as well as sitting and lying events performed by adults with unilateral lower limb absence in controlled laboratory simulations. Multiple raters are not needed in order to obtain reliable data. These data can be used to obtain a reliable record of physical behaviours for criterion-related validation of other measures such as accelerometers

Reliability and validity of the activPAL for measuring stepping and reclining in unilateral lower limb amputees

Introduction: Valid, reliable measurement of physical behaviours in adults with limb absence is essential to accurately describe physical behaviour patterns and intervention effects. Purpose: To assess parallel forms reliability and criterion-related validity of the activPAL for measuring steps and reclining time in simulated lifestyle activities in adults with unilateral lower limb absence. Methods: 15 adults completed three circuits of simulated kitchen work, sitting, lying and purposeful walking on level ground and stairs. Three trained raters independently analysed video recorded trials for incidental stepping, purposeful stepping and reclining. Simultaneous data were obtained from two activPAL monitors placed on the sound and prosthetic side. Data were analysed using oneway intraclass correlation coefficients (ICC; parallel forms reliability), and with Pearson correlations, oneway repeated ANOVAs, and Cohen's d (criterion-related validity). Results: Parallel forms reliability (prosthetic side vs. sound side) was poor for incidental steps (ICC = .05, d = 0.41) but acceptable for all other measures (ICC = .69-.98; d = 0.02-0.17). Correlations between direct observation and activPAL ranged from r = .65-.98 (activPAL on sound side) and from r = .30-.99 (activPAL on prosthetic side). Mean differences between observed measures and activPAL measures were generally large for all stepping variables (d = 0.56-4.22); observed mean scores were systematically higher than from the activPAL. Correlations were higher for reclining time (r = .98- .99), and differences were smaller (d = 0.25-0.28), although the pattern was similar (observed scores were higher). Conclusions: activPAL data from the sound side and prosthetic side are similar for adults with unilateral lower limb absence. Validity of the activPAL in this population seems poor in simulated lifestyle activities. These results may be at least partly due to the brief sampling period or the simulated activity protocol