Cancer and changes in facial appearance : a meta-ethnography of qualitative studies

Introduction: Living with an altered facial appearance as a result of treatment for cancer requires considerable psychological adjustment. As such it is essential that health care professionals understand the lived experience of people affected. This systematic review provides a metaethnography of studies that have explored the experience of changed facial appearance as a result of cancer. Methods: A search of four databases (Web of Science, CINAHL, PsycInfo and Scopus) took place using terms relating to qualitative research, cancer, and changed facial appearance. Thirteen studies were identified, appraised and included in the synthesis. The findings and interpretations within the studies were subject to meta-ethnography procedures so as to elicit novel cross cutting themes. Findings: The experience of changed facial appearance after cancer was clustered into three contexts. In the context of the disease, subthemes were the primacy of survival, the changing relationship with the disease and the impact of the care team on the experience of changed appearance. In the context of the social world, subthemes were positive reactions, negative reactions and coping strategies. In the context of the self, subthemes were the self under attack, self-to-self relating, the self in the world and rebuilding the self. Conclusions: The findings indicate that healthcare professionals must conduct holistic assessments, so as to fully recognise and where necessary address the impact upon self. The meta-ethnography shows that the experience of facial appearance change following cancer is complex and requires awareness of a number of theoretical areas including identity construction, social support, stigmatisation, and the specific literature on visible difference

Genetic variation within the IL-18 system and its association with cardiovascular disease and obesity.

Background and Aims: The interleukin 18 (IL-18) system consists of a pro inflammatory cytokine (IL-18), a naturally occurring inhibitor (IL-18BP), and a dimeric receptor. IL-18 has been implicated in many autoimmune conditions, with elevated plasma levels predicting future risk of heart disease in healthy individuals. IL-18 also appears to have metabolic consequences, with M8 / mice having higher bodyweight, attributable to increased feeding. The central hypothesis of this work was that genetic variation within both IL-18 and IL18BP, that influenced their circulating levels, would be associated with individual risk for both heart disease and obesity. This was tested by measuring IL-18 levels in several study groups and accessing their correlation with numerous single nucleotide polymorphisms (SNPs) (chosen using a tagging SNP (tSNP) methodology) within both genes. Any effects (either single SNP or haplotypic) were then assessed directly using quantitative PCR (QPCR). Results: For both IL18 and ILI8BP, tSNP sets were chosen that captured greater than 90% of the common genetic variation seen in a representative European Caucasian sample. Their association with levels of IL-18 and interleukin 18 binding protein (IL-18BP) were assessed in healthy and diseased individuals genetic variation in IL-18 only was associated with differences in plasma IL-18 (and free IL-18 (fIL-18)) levels in all cohorts. Carriage of the rare allele of /L/S-5848 T>C was associated with, on average across all study groups, 44% higher IL-18 levels than TT homozygotes. There was also a haplotypic effect, with a common haplotype---hGTATA (frequency of 20%)---being associated with 30% lower IL-18 levels. The effect was consistently of greater magnitude in diseased than healthy individuals. Despite IL-18 levels being elevated in those individuals who went on to suffer an myocardial infarction (MI) over 15 yr of follow-up (277.6 pg/ml vs. 239.6 pg/ml, p=0.05), there was no significant difference in genotype, or haplotype, frequencies in those who had heart disease compared to those who did not. No consistent association between BMI/obesity and IL-18 levels was observed, however, in two of the study groups genetic variation in IL18 was associated with significant differences in body mass index (BMI). Overall, hGTATA was associated with a 9% higher BMI, equating to a 7 kg greater body weight for an average male. In in vitro studies of IL-18 expression in healthy, male hGTATA carriers, no significant difference in 1L-18 messenger RNA (mRNA) concentrations were observed when compared to hGCATA controls. Conclusion: The data presented here disagrees with previously published results, showing no role for variation within IL18 in establishing heart disease risk. However there are novel findings that suggest it may play a role in weight control. Given that these effects appear not to be mediated through plasma IL-18 levels, the identification of individuals through genetic testing may be especially relevant

HIF-mediated innate immune responses: cell signaling and therapeutic implications

Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs) are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out

The value of character-based judgement in the professional domain

Dimensions of character are often overlooked in professional practice at the expense of the development of technical competence and operational efficiency. Drawing on philosophical accounts of virtue ethics and positive psychology, the present work attempts to elevate the role of ‘good’ character in the professional domain. A ‘good’ professional is ideally one that exemplifies dimensions of character informed by sound judgement. A total of 2340 professionals, from five discrete professions, were profiled based on their valuation of qualities pertaining to character and judgement. Profile differences were subsequently examined in the self-reported experience of professional purpose towards a wider societal ‘good’. Analysis of covariance, controlling for stage of career, revealed that professionals valuing character reported higher professional purpose than those overweighting the importance of judgement or valuing neither character nor judgement, F(3, 2054) = 7.92, p < .001. No differences were found between the two groups valuing character, irrespective of whether judgement was valued simultaneously. This profiling analysis of entry-level and in-service professionals, based on their holistic character composition, paves the way for fresh philosophical discussion regarding what constitutes a ‘good’ professional and the interplay between character and judgement. The empirical findings may be of substantive value in helping to recognise how the dimensions of character and judgement may impact upon practitioners’ professional purpose

A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia

Background. Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. Methods. Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. Results. During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. Conclusions. The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection

Calcium and magnesium supplementation of ewes grazing pasture did not improve lamb survival

Context: Clinical deficiencies of calcium and magnesium may result in the metabolic disorders hypocalcaemia and hypomagnesaemia, resulting in ewe and lamb mortality. However, the contribution of subclinical deficiencies to perinatal lamb mortality in grazing flocks is unclear. Aims: To test the hypothesis that calcium and magnesium supplementation during the lambing period would increase lamb survival to marking age. Methods: In 2017, an on-farm study used five flocks across New South Wales, South Australia and Western Australia. On each farm, twin-bearing mature Merino ewes (n = 400–600) grazing pasture were allocated to two replicates of control and supplemented treatments. The supplemented groups were offered 30 g/ewe per day of a loose lick containing magnesium chloride (MgCl2(H2O)6), calcium sulfate (CaSO4·(H2O)2, and salt (NaCl), in the ratio 12.5:32.5:55.0, designed to have a low dietary cation–anion difference (−390 meq/100 g). A second study was conducted in 2018 on one farm to test the form of supplement. This study used two replicates of three treatments: control; a low-dietary cation–anion difference supplement as used in 2017; and a standard lime, Causmag (calcined MgO) and salt loose mix (ratio 1:1:1). Mature twin-bearing composite ewes (n = 600) were allocated to groups and those supplemented were offered minerals for the last month of pregnancy and during the lambing period. Blood and urine samples were collected in both experiments for analyses of mineral concentrations. Key results: In the 2017 study, only two flocks consumed >10 g/ewe of supplement per day, and supplementation did not increase lamb survival to marking age in these flocks. In the 2018 study, the mean consumption of supplement was 18 or 20 g/ewe per day. Of non-supplemented ewes, 61% were deficient in plasma calcium (≤90 mg/L) and 17% were deficient in magnesium (≤18 mg/L) at Day 140 after the start of joining. Lamb survival was not increased by supplementation and was 77 ± 3.8% in both treatments. Conclusions: Calcium and magnesium supplementation did not increase lamb survival. Implications: Lamb survival was not increased by calcium and magnesium supplementation; however, evaluation under a wider range of grazing conditions with adequate supplement intake is required

Use of control to maintain period-1 motions during wind-up or wind-down operations of an impacting driven beam

We consider the dynamical response of a thin beam held fixed at one end while excited by an external driving force. A motion limiting constraint, or stop, causes the beam to impact. During wind-up or wind-down operations, in which the driving frequency is continuously altered, the system can undergo complicated motions close to the value of frequency at which impacts may first occur, the grazing bifurcation. In this region, the beam may experience several impacts within a long period-repeating solution or even chaotic behavior which, in practical terms, may be undesirable to the long-term integrity of the system. The first task is to identify the zones in the space of parameters (forcing amplitude or, alternatively, the gap between the beam and the stop) in which period-1 motions can be guaranteed. In this paper, in the areas in which complicated or chaotic motion occurs, a control strategy is proposed which stabilises unstable period-1 motions. As a consequence, numerical simulations indicate that, for any choice of parameter in the range, simple period-1 motions can be maintained, limiting the number of impacts (together with their velocity)

Moderate deviations for random field Curie-Weiss models

The random field Curie-Weiss model is derived from the classical Curie-Weiss model by replacing the deterministic global magnetic field by random local magnetic fields. This opens up a new and interestingly rich phase structure. In this setting, we derive moderate deviations principles for the random total magnetization $S_n$, which is the partial sum of (dependent) spins. A typical result is that under appropriate assumptions on the distribution of the local external fields there exist a real number $m$, a positive real number $\lambda$, and a positive integer $k$ such that $(S_n-nm)/n^{\alpha}$ satisfies a moderate deviations principle with speed $n^{1-2k(1-\alpha)}$ and rate function $\lambda x^{2k}/(2k)!$, where $1-1/(2(2k-1)) < \alpha < 1$.Comment: 21 page

Hypoxia modulates platelet purinergic signalling pathways.

BACKGROUND:  Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. METHODS:  Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. RESULTS:  Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. CONCLUSION:  Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation

An experimental study of the impulse response of a vibro-impacting cantilever beam

The dynamics of a vibro-impacting cantilever beam experiment using an impact load cell is considered. The signal recorded from the cell produces spike train -type data. The issues related to the analysis of such data are discussed; particularly the sampling rate and threshold values. For vibro-impact motion of the beam, the duration of impacts is investigated by using a time of contact measure. The implications are discussed for vibro-impact systems mathematically modelled by using instantaneous impact assumptions (coefficient of restitution). Using the load cell to measure impact forces for the beam system is also considered. Then a delay reconstruction of the dynamics of the system by using interspike intervals is considered. It is demonstrated how this process is effected by the influence of noise and the data-acquision process using numerical simulations of the experimental data. It is shown how simple periodic motions can be identified by using a probability density approach and possible future research is highlighted