Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation

The p63 transcription factor (TP63) is critical in development, growth and differentiation of stratifying epithelia. This is highlighted by the severity of congenital abnormalities caused by TP63 mutations in humans, the dramatic phenotypes in knockout mice and de-regulation of TP63 expression in neoplasia altering the tumour suppressive roles of the TP53 family. In order to define the normal role played by TP63 and provide the basis for better understanding how this network is perturbed in disease, we used chromatin immunoprecipitation combined with massively parallel sequencing (ChIP-seq) to identify >7500 high-confidence TP63-binding regions across the entire genome, in primary human neonatal foreskin keratinocytes (HFKs). Using integrative strategies, we demonstrate that only a subset of these sites are bound by TP53 in response to DNA damage. We identify a role for TP63 in transcriptional regulation of multiple genes genetically linked to cleft palate and identify AP-2alpha (TFAP2A) as a co-regulator of a subset of these genes. We further demonstrate that AP-2gamma (TFAP2C) can bind a subset of these regions and that acute depletion of either TFAP2A or TFAP2C alone is sufficient to reduce terminal differentiation of organotypic epidermal skin equivalents, indicating overlapping physiological functions with TP63.

Cancer-related fatigue:A critical appraisal

This aim of this systematic review was to determine the prevalence and pattern of cancer-related fatigue (CRF), and identify factors associated with its development. Relevant literature was identified through an electronic database search using specified keywords. Included studies investigated CRF in adult cancer patients using a multidimensional fatigue measure. The methodological quality was assessed using six published standards. CRF is apparent both during and after anti-cancer therapy, however, the prevalence of CRF varied between studies. The variables associated with the development and persistence of CRF remain to be identified. Inconsistencies were evident in the pattern of CRF and its associated factors. This is likely to have arisen from the inherent difficulties in the measurement of a subjective sensation, further complicated by the myriad of outcome measures used. More methodologically sound research; assessing CRF from the commencement of therapy, considering all pertinent variables is needed.

Deconstructing national leadership: Politicians’ accounts of electoral success and failure in the Irish Lisbon Treaty referenda

The Self Categorization approach to national leadership proposes that leaders rhetorically construct national identity as essentialized and inevitable in order to consensualize and mobilize the population. In contrast, discursive studies have demonstrated how national politicians flexibly construct the nation to manage their own accountability in local interactions, though this in turn has neglected broader leadership processes. The present paper brings both approaches together to examine how and when national politicians construct versions of national identity in order to account for their failure as well as success in mobilizing the electorate. Eight semi-structured conversational style interviews were conducted with a strategic sample of eight leading Irish politicians on the subject of the 2008/2009 Irish Lisbon Treaty referenda. Using a Critical Discourse Psychology approach, the hegemonic repertoire of the ‘settled will’
of the informed and consensualized Irish nation was identified across all interviews. Politicians either endorsed the ‘settled will’ repertoire as evidence of their successful leadership, or rejected the repertoire by denying the rationality or unity of the populace to account for their failure. Our results suggest national identity is only constructed as essentialized and inevitable to the extent that it serves a strategic political purpose.

Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica:Expansion of a repertoire of virulence-associated factors

Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser[downward arrow]His motif for autocatalytic cleavage by cathepsin Ls were preserved.

International Projects and Cross-Cultural Adjustment of British Expatriates in Middle East: A Qualitative Investigation of Influencing Factors

Increased globalisation within the British AEC (Architectural, Engineering and Construction) sector has increased the need for companies to transfer staff to manage their overseas operations. To be able to perform abroad, expatriates must harmonise themselves to the conditions prevailing in the host country. These include getting accustomed to living, working and interacting with the host country nationals. The process is commonly referred to as 'cross-cultural adjustment'. Various factors influence the process of adjustment. In order to identify these issues, a qualitative study was undertaken, which mainly comprised of comprehensive literature review, individual interviews and focus group discussion with British expatriates working on international AEC assignments in Middle Eastern countries. Through interpretative approach, the current study aims to understand the concept of cross-cultural adjustment of British Expatriates based in Middle East and their influencing factors.

The findings suggest that success of expatriation does not entirely rest on an expatriate's ability but also on organisational support and assistance that expatriates receive prior to and during the assignment. Organisational factors such as selection mechanisms, job design, training, logistical and social support, mentoring, etc., influence various facets of expatriate adjustment. Striking cultural contrasts between British and Arab culture both in work and non work situations also dictate the level of support required by the expatriate, suggesting that relocation to less developed, remote or politically unstable regions, demands additional support and consideration by the parent company. This study is relevant to the AEC companies employing British expatriates, who need to be cognisant of the issues highlighted above to make rational and informed decisions when handling international assignments in the Middle East.

Integrating textual analysis and evidential reasoning for decision making in Engineering design

Decision making is an important element throughout the life-cycle of large-scale projects. Decisions are critical as they have a direct impact upon the success/outcome of a project and are affected by many factors including the certainty and precision of information. In this paper we present an evidential reasoning framework which applies Dempster-Shafer Theory and its variant Dezert-Smarandache Theory to aid decision makers in making decisions where the knowledge available may be imprecise, conflicting and uncertain. This conceptual framework is novel as natural language based information extraction techniques are utilized in the extraction and estimation of beliefs from diverse textual information sources, rather than assuming these estimations as already given. Furthermore we describe an algorithm to define a set of maximal consistent subsets before fusion occurs in the reasoning framework. This is important as inconsistencies between subsets may produce results which are incorrect/adverse in the decision making process. The proposed framework can be applied to problems involving material selection and a Use Case based in the Engineering domain is presented to illustrate the approach. © 2013 Elsevier B.V. All rights reserved.

An Investigation towards colossal success of Larsen and Toubro Limited: Human resource management perspective

Larsen and Toubro (L&T) Limited is India’s largest construction conglomerate. L&T’s expertise is harnessed to execute high value projects that demand adherence to stringent timelines in a scenario where disparate disciplines of engineering are required to be coordinated on a critical path. However, no company can acquire such a feat without systematic management of its human resource. An investigation on the human resource management practices in orienting L&T’s success can help to identify some of the ethical human resource practices, especially in the context of Indian market. Accordingly, a well-designed employee satisfaction survey was conducted for assessment of the HRM practices being followed in L&T. Unlike other companies, L&T aims to meet the long-term needs of its employees rather than short-term needs. There were however few areas of concerns, such as yearly appraisal system and equality to treat the employees. It is postulated that the inequality to treat the male and female employees is primarily a typical stereotype due to the fact that construction is conventionally believed to be a male dominant activity. A periodic survey intended to provide 360° feedback system can help to avoid such irregularities. This study is thus expected to provide healthy practices of HRM to nurture the young talents of India. This may help them to evaluate their decisions by analyzing the complex relationship between HRM practices and output of an organization.

Energy: lessons from devolution

Geraint Ellis and Richard Cowell explain the findings of the ‘Delivering renewable energy under devolution’ project, including some reasons for Scotland’s lead.

The UK has seen massive increases in renewable energy since 1998, with installed capacity growing from 2,600 MW to 12,300 MW in 2011. This has coincided with devolution and it is within Northern Ireland, Scotland and Wales that the greatest increases have been seen.

As devolved administrations now host half of the UK’s renewable energy capacity, their policies are critical to achieving the broader UK targets. This also provides a fascinating insight into what sort of approach works best, and why. This has been the focus of a two-year study, funded by the Economic and Social Research Council, involving universities from across the UK, which indicates that Scotland is leading the way on renewable energy.

All devolved governments have offered significant support to renewable energy but have different degrees of powers in relation to energy. Scotland’s success seems to be based on the centrality of energy issues to current political aspirations, particularly the SNP, but also has cross-party support. The research suggests that the consensus on the importance of renewable energy amongst élite interests in Scotland helps to explain why Scottish governments have been empowered and enabled to make robust use of the powers available.

As it has achieved successful growth in the sector, this too helps cultivate credibility among key business interests and gives increased leverage to its position in policy discussions with the UK Government. Scotland has been more consistent over time in presenting the expansion of renewable energy as a national economic agenda, rather than just an environmental or rural development agenda. The availability of larger, windy, but relatively less contested sites for onshore wind in Scotland has meant that more projects went through central consenting procedures rather than local planning authorities. Its enhanced support for wave and tidal power technologies is also notable. These political conditions have been harder to find in the rest of the UK, making progress a little more uncertain.

Northern Ireland has used its powers (which are more extensive than Scotland’s) to facilitate small-scale renewables and bio-fuel processes, with its liberalised planning regime offering an initial boost to expanding capacity.

This has contrasted with the position in Wales, which has least control over energy but the Welsh Government has adopted a more innovative approach to strategic spatial zoning; this appears to have pulled in a larger volume of onshore wind development interest than could be expected in a comparable region of England. A downside of the Welsh approach appears to be the fact that the concentration of these wind projects in these zones has triggered public opposition and political conflict.

It therefore appears that the powers available to the devolved governments do not seem to determine which country has been able to make greatest headway, with broader political commitments being more significant. Despite this, the research does not conclude that the actions and activities undertaken by the devolved governments are necessarily the most important factors in shaping the development of renewable energy in the UK. This is because devolution is still a relatively new dimension of energy governance in the UK and decisions affecting key drivers for renewable energy investment are still made mainly in Westminster, with the Treasury exercising close budgetary control. In all areas of the UK, grid capacity expansion remains slow to achieve. The major growth in offshore wind to date has been driven mainly by Westminster and cross-UK bodies with the most significant capacity growth being in English territorial waters.

Weaning from mechanical ventilation: a scoping review of qualitative studies

Background; Weaning from mechanical ventilation is influenced by patient, clinician, and organizational factors.

Objective: To identify factors that may influence weaning and adoption of weaning strategies and tools, clinicians’ perceptions of weaning strategies, and weaning experiences of patients and patients’ families.

Method: A scoping review of indexed and nonindexed publications (1990–2012) was done. Qualitative studies of health care providers, patients, and patients’ families involved in weaning were included. Two investigators independently screened 8350 publications and extracted data from 43 studies. Study themes were content analyzed to identify common categories and themes within the categories.

Results: The study sample consisted of nurses in 15 studies, nurses and patients in 1 study, various health care providers in 11, patients in 10, and physicians in 4. Categories identified were as follows: for nurses, role or scope of practice, informing decision making, and influence on weaning outcome; for health care providers, factors influencing weaning decisions or use of protocols, role or scope of practice related to weaning, and organizational structure or practice environment; for patients, experience of mechanical ventilation and weaning, experience of the intensive care environment, psychological phenomena, and enabling success in weaning; and for physicians, tools or factors to facilitate weaning decisions and perceptions of nurses’ role and scope of practice.

Conclusions: Important issues identified were perceived importance of interprofessional collaboration and communication, need to combine subjective knowledge of the patient with objective clinical data, balancing of weaning systematization with individual needs, and appreciation of the physical and psychological work of weaning.

The relationship between BMI and the prescription of anti-obesity medication according to social factors: a population cross sectional study

Background: Obesity is a global public health problem. There are a range of treatments available with varying short and long term success rates. One option is the use of anti-obesity medication the prescription of which has increased dramatically in recent years. Despite this, little is known about the individual and GP practice factors that influence the prescription of anti-obesity medication. Methods: Multi-level logistic regression analysis was used to investigate factors associated with the prescription of anti-obesity medication in Northern Ireland using a population primary care prescribing database (~1.5 million people aged 16+ years) during 2009/10. Results: While 25.0% of people are obese, only 1.3% (2.1% of females, 0.6% of males) received anti-obesity medication. The relationship between medication rates and age differed by gender (P < 0.001) with prescriptions higher in younger females and older males. Prescribing of anti-obesity medication reflected obesity prevalence across urban/rural areas and deprivation. There was an unexplained two-fold difference, between the 25th and 75th percentile, in the GP practice prescription of anti-obesity medication. Conclusions: There is evidence of relative under-prescribing in males compared to females despite a similar prevalence of obesity. While the prevalence (and presumably the health consequences) of obesity worsens with age, younger females are more likely to be prescribed anti-obesity medication. This suggests an element of patient demand. Educational material to improve the understanding of the role of anti-obesity medication, for patients and practitioners, is recommended. But further study is needed to understand the factors responsible for the variation in prescribing between GP practices.

The Effectiveness of Weight Management Interventions in Breastfeeding Women—A Systematic Review and Critical Evaluation

Background: The postpartum period is a vulnerable time for excess weight retention, particularly for the increasing number of women who are overweight at the start of their pregnancy and subsequently find it difficult to lose additional weight gained during pregnancy. Although postpartum weight management interventions play an important role in breaking this potentially vicious cycle of weight gain, the effectiveness of such interventions in breastfeeding women remains unclear. Our aim was to systematically review the literature about the effectiveness of weight management interventions in breastfeeding women.

Methods: Seven electronic databases were searched for eligible papers. Intervention studies included were carried out exclusively in breastfeeding mothers, ≤2 years postpartum and with a body mass index greater than 18.5 kg/m2, with an outcome measure of change in weight and/or body composition.

Results: Six studies met the selection criteria, and were stratified according to the type of intervention and outcome measures. Despite considerable heterogeneity among studies, the dietary-based intervention studies appeared to be the most efficacious in promoting weight loss; however, few studies were tailored toward the needs of breastfeeding women.

Conclusions: Weight management interventions which include an energy-restricted diet may play a key role in successful postpartum weight loss for breastfeeding mothers.

Quality Management and Managerialism in Healthcare:: A Critical Historical Survey

Quality Management and Managerialism in Healthcare creates a comprehensive and systematic international survey of various perspectives on healthcare quality management together with some of their most pertinent critiques. Chapter one starts with a general discussion of the factors that drove the introduction of management paradigms into public sector and health management contexts in the mid to late 1980s. Chapter two explores the rise of risk awareness in medicine; which, prior to the 1980s, stood largely in isolation to the implementation of managerial performance targets. Chapter three investigates the widespread adoption of performance management and clinical governance frameworks during the 1980s and 1990s. This is followed by Chapters four and five which examine systems based models of patient safety and the evidence-based medicine movement as exemplars of managerial perspectives on healthcare quality. Chapter six discusses potential future avenues for the development of alternative perspectives on quality of care which emphasise workforce involvement. The book concludes by reviewing the factors which have underpinned the managerialist trajectory of healthcare management over the past decades and explores the potential impact of nascent technologies such as 'connected health' and 'telehealth' on future developments.

When are total concentrations not total? Factors affecting geochemical analytical techniques for measuring element concentrations in soil

Inductively coupled plasma (ICP) following aqua regia digestion and X-ray fluorescence (XRF) are both geochemical techniques used to determine ‘total’ concentrations of elements in soil. The aim of this study is to compare these techniques, identify elements for which inconsistencies occur and investigate why they arise. A study area (∼14,000 km2) with a variety of total concentration controls and a large geochemical dataset (n = 7950) was selected. Principal component analysis determined underlying variance in a dataset composed of both geogenic and anthropogenic elements. Where inconsistencies between the techniques were identified, further numerical and spatial analysis was completed. The techniques are more consistent for elements of geogenic sources and lead, whereas other elements of anthropogenic sources show less consistency within rural samples. XRF is affected by sample matrix, while the form of element affects ICP concentrations. Depending on their use in environmental studies, different outcomes would be expected from the techniques employed, suggesting the choice of analytical technique for geochemical analyses may be more critical than realised.

A critical ethnography of communication processes involving the management of oral chemotherapeutic agents by patients with a primary diagnosis of colorectal cancer: study protocol

Aim
To describe the protocol used to examine the processes of communication between health professionals, patients and informal carers during the management of oral chemotherapeutic medicines to identify factors that promote or inhibit medicine concordance.

Background
Ideally communication practices about oral medicines should incorporate shared decision-making, two-way dialogue and an equality of role between practitioner and patient. While there is evidence that healthcare professionals are adopting these concordant elements in general practice there are still some patients who have a passive role during consultations. Considering oral chemotherapeutic medications, there is a paucity of research about communication practices which is surprising given the high risk of toxicity associated with chemotherapy.

Design
A critical ethnographic design will be used, incorporating non-participant observations, individual semi-structured and focus-group interviews as several collecting methods.

Methods
Observations will be carried out on the interactions between healthcare professionals (physicians, nurses and pharmacists) and patients in the outpatient departments where prescriptions are explained and supplied and on follow-up consultations where treatment regimens are monitored. Interviews will be conducted with patients and their informal carers. Focus-groups will be carried out with healthcare professionals at the conclusion of the study. These several will be analysed using thematic analysis. This research is funded by the Department for Employment and Learning in Northern Ireland (Awarded February 2012).

Discussion
Dissemination of these findings will contribute to the understanding of issues involved when communicating with people about oral chemotherapy. It is anticipated that findings will inform education, practice and policy.