Expression of the NF-κB inhibitor A20 is altered in the Cystic Fibrosis epithelium

Research Question: A20 is an LPS-inducible, cytoplasmic zinc finger protein, that inhibits TLR-activated NF-?B signalling by deubiquitinating TRAF6. A20 action is facilitated by complex formation with RNF11, Itch and TAX1BP1. This study investigates if the expression of A20 is altered in the chronically inflamed Cystic Fibrosis (CF) airway epithelium.

Methods: Nasal epithelial cells from CF patients (F508del homozygous), non-CF controls and immortalised epithelial cells (16HBE14o- and CFBE41o-) were stimulated with LPS. Cytoplasmic expression of A20 and expression of NF-?B subunits was analysed. Formation of the A20 ubiquitin editing complex was also investigated.

Results: In CFBE41o-, peak LPS-induced A20 expression was delayed compared with 16HBE14o- and fell significantly below basal levels 12-24 h after LPS stimulation. This was confirmed in primary CF airway cells. Additionally, a significant inverse relationship between A20 and p65 expression was observed. Inhibitor studies showed that A20 does not undergo proteasomal degradation in CFBE41o-. A20 interacted with TAX1BP1, RNF11 and TRAF6 in 16HBE14o- cells, but these interactions were not observed in CFBE41o-.

Conclusion: he expression of A20 is significantly altered in CF and important interactions with complex members and target proteins are lost, which may contribute to the state of chronic NF-?B-driven inflammation.

Monochloroacetic acid and 60% salicylic acid as a treatment for simple plantar warts:effectiveness and mode of action

Monochloroacetic acid crystals and 60% salicylic acid ointment was found to be more effective than placebo as a treatment for simple plantar warts in a double blind study on 57 patients. Nineteen (66%) patients in the active treatment group compared with five (18%) patients in the placebo group were cured after 6 weeks (P = 0.002). The active treatment was associated with a significantly higher cure rate 6 months after entry (P = 0.04). Treatments were well tolerated. IgG or IgM antibodies or both to human papilloma virus (HPV) types 1 or 2 or both were detected significantly more frequently in the actively treated group 6 weeks after entry (P = 0.0005). Twelve (50%) patients considered to be cured had no detectable secondary immune response. Our results suggest that cure does not depend primarily on the humoral system but rather on mechanical destruction of wart tissue, or occurs as a result of cell mediated immunity.

Assessing the sensitivity and specificity of fish community indicators to management action

We assessed ten trophodynamic indicators of ecosystem status for their sensitivity and specificity to fishing management using a size-resolved multispecies fish community model. The responses of indicators to fishing depended on effort and the size selectivity (sigmoid or Gaussian) of fishing mortality. The highest specificity against sigmoid (trawl-like) size selection was seen from inverse fishing pressure and the large fish indicator, but for Gaussian size selection, the large species indicator was most specific. Biomass, mean trophic level of the community and of the catch, and fishing in balance had the lowest specificity against both size selectivities. Length-based indicators weighted by biomass, rather than abundance, were more sensitive and specific to fishing pressure. Most indicators showed a greater response to sigmoid than Gaussian size selection. Indicators were generally more sensitive at low levels of effort because of nonlinear sensitivity in trophic cascades to fishing mortality. No single indicator emerged as superior in all respects, so given available data, multiple complementary indicators are recommended for community monitoring in the ecosystem approach to fisheries management.

Economic aspects of pharmacotherapy for chronic constipation

Constipation is one of the most common digestive complaints. It is a symptom, not a disease. The subjectivity that this involves means that assessments of clinical epidemiology, socioeconomic costs and pharmacotherapy are difficult, since there is no definition of 'normal' bowel habit. Although constipation can affect all ages, the problem increases with age, and is of particular concern for those who are frail and in long term care. Cultural influences may affect the prevalence in older people. Drug therapy of constipation cannot be considered in isolation, since there are issues in the prevention of constipation and the principles of good management that also apply. Furthermore, some consideration of the pathophysiology and diagnosis is important. This is because a number of remediable causes can be identified, and the diagnostic process involves patient education, which in turn may be effective in reducing costs. It is the complaint of constipation which leads either to self-medication or to consultation with the medical profession. Both of these courses of action have a significant influence on utilisation of laxatives (cathartics), obtained both over-the-counter and by prescription. Although there are a large number of laxative preparations available, therapy has changed little in half a century. Costs may vary considerably, and with such a significant problem there is a need for comparative studies. However, study methodologies are difficult, and a significant placebo response may be found. Education and preventive measures have been shown to reduce laxative use and costs in institutions. Unfortunately, there are few comparative studies of individual laxatives and even fewer cost-effectiveness studies. Those that there are have been based in institutions, and so extrapolation to other situations may be difficult. In general, little attention is given to constipation. It is, however, an area with significant resource implications in which education and preventive measures have been shown to be beneficial. Even so, there is still a need for good comparative studies, particularly where cost effectiveness is concerned.

'Sometimes I wish I was an "ex" ex-prisoner': identity processes in the collective action participation of former prisoners in Northern Ireland

Since the signing of the Northern Ireland peace agreement a plethora of community based prisoner self-help organisations have been established wherein former prisoners staff, manage and deliver services to colleagues. By forging and maintaining their collective identities through community based mutual aid, members of these self-help organisations have progressed to create not only individual change/assistance but have also developed and evolved to tackle serious wider social issues which impact on the members of their organisations. This article critically analyses how the conditions of a post conflict society can influence both the development and evolution of these organisations and also how members situate their claims about the self in the organisation and beyond. Using the social movement framework it is argued that the work of these self-help organisations have given rise to a new politics of identity … that is the ‘politically motivated’ ex-prisoner. ©2013 Taylor & Francis

Does Affirmative Action Work? Evidence from the Operation of Fair Employment Legislation in Northern Ireland

An affirmative action programme, established by the Fair Employment (Northern Ireland) Act 1989, has been an important attempt to ensure ‘fair participation’ in employment for both Catholics and Protestants in Northern Ireland since 1990. The programme includes detailed monitoring of the community background of employees and requires employers to undertake remedial action where fair participation is not evident. Agreements were concluded between the regulatory agency and many employers specifying what affirmative action measures were required. Based on the annual monitoring returns submitted between 1990 and 2005, this article evaluates the effectiveness of the affirmative action programme in promoting fair employment participation using fixed effects models. The analysis shows that there has been a general shift towards workforce integration in Northern Ireland but the increase of under-represented groups in agreement concerns is greater than in concerns with no agreement. The success of agreements, however, is limited to certain industrial sectors and medium-sized enterprises.

Three-dimensional delayed-detonation models with nucleosynthesis for type ia supernovae

We present results for a suite of 14 three-dimensional, high-resolution hydrodynamical simulations of delayed-detonation models of Type Ia supernova (SN Ia) explosions. This model suite comprises the first set of three-dimensional SN Ia simulations with detailed isotopic yield information. As such, it may serve as a data base for Chandrasekhar-mass delayed-detonation model nucleosynthetic yields and for deriving synthetic observables such as spectra and light curves. We employ aphysically motivated, stochastic model based on turbulent velocity fluctuations and fuel density to calculate in situ the deflagration-to-detonation transition probabilities. To obtain different strengths of the deflagration phase and thereby different degrees of pre-expansion, we have chosen a sequence of initial models with 1, 3, 5, 10, 20, 40, 100, 150, 200, 300 and 1600 (two different realizations) ignition kernels in a hydrostatic white dwarf with a central density of 2.9 × 10 g cm, as well as one high central density (5.5 × 10 g cm) and one low central density (1.0 × 10 g cm) rendition of the 100 ignition kernel configuration. For each simulation, we determined detailed nucleosynthetic yields by postprocessing10 tracer particles with a 384 nuclide reaction network. All delayed-detonation models result in explosions unbinding thewhite dwarf, producing a range of 56Ni masses from 0.32 to 1.11M. As a general trend, the models predict that the stableneutron-rich iron-group isotopes are not found at the lowest velocities, but rather at intermediate velocities (~3000×10 000 km s) in a shell surrounding a Ni-rich core. The models further predict relatively low-velocity oxygen and carbon, with typical minimum velocities around 4000 and 10 000 km s, respectively. © 2012 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.

Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns

Slower postnatal growth is an important predictor of adverse neurodevelopmental outcomes in infants born preterm. However, the relationship between postnatal growth and cortical development remains largely unknown. Therefore, we examined the association between neonatal growth and diffusion tensor imaging measures of microstructural cortical development in infants born very preterm. Participants were 95 neonates born between 24 and 32 weeks gestational age studied twice with diffusion tensor imaging: scan 1 at a median of 32.1 weeks (interquartile range, 30.4 to 33.6) and scan 2 at a median of 40.3 weeks (interquartile range, 38.7 to 42.7). Fractional anisotropy and eigenvalues were recorded from 15 anatomically defined cortical regions. Weight, head circumference, and length were recorded at birth and at the time of each scan. Growth between scans was examined in relation to diffusion tensor imaging measures at scans 1 and 2, accounting for gestational age, birth weight, sex, postmenstrual age, known brain injury (white matter injury, intraventricular hemorrhage, and cerebellar hemorrhage), and neonatal illness (patent ductus arteriosus, days intubated, infection, and necrotizing enterocolitis). Impaired weight, length, and head growth were associated with delayed microstructural development of the cortical gray matter (fractional anisotropy: P <0.001), but not white matter (fractional anisotropy: P = 0.529), after accounting for prenatal growth, neonatal illness, and brain injury. Avoiding growth impairment during neonatal care may allow cortical development to proceed optimally and, ultimately, may provide an opportunity to reduce neurological disabilities related to preterm birth.

The expression of pain in infants and toddlers:developmental changes in facial action

Age-related changes in the facial expression of pain during the first 18 months of life have important implications for our understanding of pain and pain assessment. We examined facial reactions video recorded during routine immunization injections in 75 infants stratified into 2-, 4-, 6-, 12-, and 18-month age groups. Two facial coding systems differing in the amount of detail extracted were applied to the records. In addition, parents completed a brief questionnaire that assessed child temperament and provided background information. Parents' efforts to soothe the children also were described. While there were consistencies in facial displays over the age groups, there also were differences on both measures of facial activity, indicating systematic variation in the nature and severity of distress. The least pain was expressed by the 4-month age group. Temperament was not related to the degree of pain expressed. Systematic variations in parental soothing behaviour indicated accommodation to the age of the child. Reasons for the differing patterns of facial activity are examined, with attention paid to the development of inhibitory mechanisms and the role of negative emotions such as anger and anxiety.

Pain expression in neonates:facial action and cry

Pain expression in neonates instigated by heel-lance for blood sampling purposes was systematically described using measures of facial expression and cry and compared across sleep/waking states and sex. From gate-control theory it was hypothesized that pain behavior would vary with the ongoing functional state of the infant, rather than solely reflecting tissue insult. Awake-alert but inactive infants responded with the most facial activity, consistent with current views that infants in this state are most receptive to environmental stimulation. Infants in quiet sleep showed the least facial reaction and the longest latency to cry. Fundamental frequency of cry was not related to sleep/waking state. This suggested that findings from the cry literature on qualities of pain cry as a reflection of nervous system 'stress', in unwell newborns, do not generalize directly to healthy infants as a function of state. Sex differences were apparent in speed of response, with boys showing shorter time to cry and to display facial action following heel-lance. The findings of facial action variation across sleep/waking state were interpreted as indicating that the biological and behavioral context of pain events affects behavioral expression, even at the earliest time developmentally, before the opportunity for learned response patterns occurs. Issues raised by the study include the importance of using measurement techniques which are independent of preconceived categories of affective response.