Identification of gene networks associated with acute myeloid leukemia by comparative molecular methylation and expression profiling

Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies.

Biomarkers of fruit and vegetable intake in Human intervention studies a systematic review

Observational evidence consistently shows that consumption of a diet rich in fruit and vegetables may offer protection against diseases such as cardiovascular disease and cancer. Assessment of dietary intake is complex and prone to many sources of error. More objective biomarkers of fruit and vegetable intake are therefore of interest. The aim of this review is to examine the usefulness of the main biomarkers of fruit and vegetable intake to act as objective indicators of compliance in dietary intervention studies. A comprehensive search of the literature was conducted using six databases. Suitable papers were selected and relevant data extracted. The papers were categorized into 3 sub-groups: whole diet interventions; mixed fruit and vegetable interventions; and studies involving individual varieties of fruits or vegetables. Ninety-six studies were included in the review. Overall, the most commonly measured, and most consistently responsive, biomarkers were the carotenoids and vitamin C. Based on the results of this systematic review, it remains prudent to measure a panel of biomarkers in fruit and vegetable intervention studies. The only possible exception to this is “fruit only” intervention studies where assessment of vitamin C alone may suffice.

A sibling-controlled, prospective study of outcomes at home and school in children with severe congenital heart disease

Objectives: The objectives of this study were to compare behaviour problems and competencies, at home and school, in 7-year-old children with congenital heart disease with a sibling control group, to examine the prospective determinants of outcome from infancy, and to explore whether any gains were maintained in our sub-group of children who had participated in a previous trial of psychological interventions in infancy.
Methods: A total of 40 children who had undergone surgery to correct or palliate a significant congenital heart defect in infancy were compared (Child Behavior Checklist) with a nearest-age sibling control group (18 participants). Comparisons were made between sub-groups of children and families who had and had not participated in an early intervention trial.
Results: Problems with attention, thought and social problems, and limitations in activity and school competencies, were found in comparison with siblings. Teacher reports were consistent with parents, although problems were of a lower magnitude. Disease, surgical, and neurodevelopmental functioning in infancy were related to competence outcomes but not behaviour problems. The latter were mediated by family and maternal mental health profiles from infancy. Limited, but encouraging, gains were maintained in the sub-group that had participated in the early intervention programme.
Conclusions: The present study is strengthened by its longitudinal design, use of teacher informants, and sibling control group. The patterns of problems and limitations discerned, and differential determinants thereof, have clear implications for interventions. We consider these in the light of our previously reported intervention trial with this sample and current outcomes at the 7-year follow-up.

Multi-Dimensional Deprivation in Ireland Among 9-Year-Olds in Ireland:An Analysis of the Growing Up in Ireland Survey’

In this paper we make use of the 9-year old wave of the Growing Up in Ireland study to analyse multidimensional deprivation in Ireland. The Alkire and Foster adjusted head count ratio approach (AHCR; 2007, 2011a, 2011b) applied here constitutes a significant improvement on union and intersection approaches and allows for the decomposition of multidimensional poverty in terms of dimensions and sub-groups. The approach involves a censoring of data such that deprivations count only for those above the specified multidimensional threshold leading to a stronger set of interrelationships between deprivation dimensions. Our analysis shows that the composition of the adjusted head ratio is influenced by a range of socio-economic factors. For less-favoured socio-economic groups dimensions relating to material deprivation are disproportionately represented while for the more advantaged groups, those relating to behavioral and emotional issues and social interaction play a greater role. Notwithstanding such variation in composition, our analysis showed that the AHCR varied systematically across categories of household type, and the social class, education and age group of the primary care giver. Furthermore, these variables combined in a cumulative manner. The most systematic variation was in relation to the head count of those above the multidimensional threshold rather than intensity, conditional on being above that cut-off point. Without seeking to arbitrate on the relative value of composite indices versus disaggregated profiles, our analysis demonstrates that there is much to be gained from adopting an approach with clearly understood axiomatic properties. Doing so allows one to evaluate the consequences of the measurement strategy employed for the understanding of levels of multidimensional deprivation, the nature of such deprivation profiles and socio-economic risk patterns. Ultimately it permits an informed assessment of the strengths and weaknesses of the particular choices made.

A methodological review of the Short Form Health Survey 36 (SF-36) and its derivatives among breast cancer survivors

Purpose: A systematic review of the validity, reliability and sensitivity of the Short Form (SF) health survey measures among breast cancer survivors.
Methods: We searched a number of databases for peer-reviewed papers. The methodological quality of the papers was assessed using the COnsenus-based Standards for the selection of health Measurement INstruments (COSMIN).
Results: The review identified seven papers that assessed the psychometric properties of the SF-36 (n = 5), partial SF-36 (n = 1) and SF-12 (n = 1) among breast cancer survivors. Internal consistency scores for the SF measures ranged from acceptable to good across a range of language and ethnic sub-groups. The SF-36 demonstrated good convergent validity with respective subscales of the Functional Assessment of Cancer Treatment—General scale and two lymphedema-specific measures. Divergent validity between the SF-36 and Lymph-ICF was modest. The SF-36 demonstrated good factor structure in the total breast cancer survivor study samples. However, the factor structure appeared to differ between specific language and ethnic sub-groups. The SF-36 discriminated between survivors who reported or did not report symptoms on the Breast Cancer Prevention Trial Symptom Checklist and SF-36 physical sub-scales, but not mental sub-scales, discriminated between survivors with or without lymphedema. Methodological quality scores varied between and within papers.
Conclusion: Short Form measures appear to provide a reliable and valid indication of general health status among breast cancer survivors though the limited data suggests that particular caution is required when interpreting scores provided by non-English language groups. Further research is required to test the sensitivity or responsiveness of the measure.

FKBPL: a marker of good prognosis in breast cancer

FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14-1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.

The effects of Chronic Lycopene Supplementation on Exercise-Induced Oxidative Stress and Glucose Homeostasis.

Lycopene can exert antioxidant effects against peripheral and cellular oxidative stress and may be associated with reduced diabetic risk. Conversely, exercise-induced free radicals are thought to underpin many of the desirable whole-body adaptations following training and the use of antioxidants within the exercise model remains debatable. PURPOSE: To investigate the effect of lycopene supplementation on oxidative stress and glucose homeostasis following acute aerobic exercise. METHOD: Twenty-eight (n=28) apparently healthy male volunteers were recruited (age 24 ± 4 years; weight 78 ± 10 kg; height 178 ± 8 cm; 2max 40 ± 7 ml·kg-1 ·min-1 ) in a randomised, single blind, placebo-controlled study. Participants were required to attend the Laboratory on two occasions: prior to and following 6 weeks of supplementation of either 10mg lycopene (LG; n=15) or placebo (PG; n=13) followed by a bout of acute exercise for one hour at 65% 2max. Exogenous glucose oxidation was then measured on an isotope ratio mass spectrometer in a sub-group of participants (n=14) following exercise, by administration of a standard oral glucose tolerance test (OGTT; 75g glucose). Venous blood samples were drawn for measurement of oxidative stress parameters, plasma glucose and insulin. RESULTS: Plasma lycopene increased in LG only (0.01 ± 0.004 vs.0.02 ± 0.007 µmol/L; P <0.05) following supplementation and remained elevated post exercise compared to PG (0.01 ± 0.004 vs. 0.02 ± 0.009 µmol/L; P <0.05). There were no changes in other markers of oxidative stress (SOD, LOOHs, F2 ISP and Alkoxyl radical) either between or within the trials, (P >0.05, respectively). A main effect for an increase in insulin was observed two hours post OGTT in the sub-groups (Pooled data, P <0.05) but trends in the HOMA scores were evident with a 57% increase for LG (2.20 ± 1.84 vs. 5.14 ± 2.5; P >0.05) and an 11% decrease for PG (2.17 ± 1.06 vs. 1.94 ± 1.53; P >0.05). No change in plasma glucose was detected at any point, or after the OGTT (P >0.05). CONCLUSION: In healthy males, lycopene supplementation had no effect on post exercise levels of ROS or markers of lipid peroxidation, despite an increase in plasma lycopene. However, lycopene supplementation may affect post exercise insulin sensitivity in response to glucose consumption, but further parallel research is required.

The working practices of Birmingham's Centre for Contemporary Cultural Studies

This article offers a history of the working practices of the Birmingham Centre for Contemporary Cultural Studies. Based on extensive interviews with former members and on research into a new archive of the Centre, housed in the Cadbury Research Library, University of Birmingham, it argues that cultural studies as practised in the 1970s was always a heterogeneous subject. The CCCS was heavily influenced by the events of 1968 when it tried to develop a new type of radical and collaborative research and teaching agenda. Despite Stuart Hall's efforts to impose a focused link between politics and academic practice, the agenda soon gave way to a series of diverse and fruitful initiatives associated with the ‘sub-groups’ model of research.

Men’s depression and suicide literacy: A nationally representative Canadian survey

Background: Male suicide prevention strategies include diagnosis and effective management of men’s depression. Fundamental to suicide prevention efforts is public awareness, which in turn, is influenced by literacy levels about men’s depression and suicide.

Aim: To examine sex differences in mental health literacy with respect to men’s depression and suicide among a cohort of Canadian respondents.

Methods: 901 English-speaking Canadian men and women completed online survey questionnaires to evaluate mental health literacy levels using 10-item D-Lit and 8-item LOSS questionnaires, which assess factual knowledge concerning men’s depression and suicide. Statistical tests (chi-square, z-test) were used to identify significant differences between sex sub-groups at 95% confidence.

Results: Overall, respondents correctly identified 67% of questions measuring literacy levels about male depression. Respondents’ male suicide literacy was significantly poorer at 53.7%. Misperceptions were especially evident in terms of differentiating men’s depressive symptoms from other mental illnesses,
estimating prevalence and identifying factors linked to male suicide. Significant sex differences highlighted that females had higher literacy levels than men in regard to male depression.

Conclusions: Implementing gender sensitive and specific programs to target and advance literacy levels about men’s depression may be key to ultimately reducing depression and suicide among men in Canada.

Informal caregiving and mental ill health – differential relationships by workload, gender, age and area-remoteness in a UK region

Informal caregiving can be a demanding role which has been shown to impact on physical, psychological and social wellbeing. Methodological weaknesses including small sample sizes and subjective measures of mental health have led to inconclusive evidence about the relationship between informal caregiving and mental health. This paper reports on a study carried out in a UK region which investigated the relationship between informal caregiving and mental ill health. The analysis was conducted by linking three datasets, the Northern Ireland Longitudinal Study, the Northern Ireland Enhanced Prescribing Database and the Proximity to Service Index from the Northern Ireland Statistics and Research Agency. Our analysis used both a subjective measure of mental ill health, i.e. a question asked in the 2011 Census, and an objective measure, whether the respondents had been prescribed antidepressants by a General Practitioner between 2010 and 2012. We applied binary logistic multilevel modelling to these two responses to test whether, and for what sub-groups of the population, informal caregiving was related to mental ill health. The results showed that informal caregiving per se was not related to mental ill health although there was a strong relationship between the intensity of the caregiving role and mental ill health. Females under 50, who provided over 19 hours of care, were not employed or worked part-time and who provided care in both 2001 and 2011 were at a statistically significantly elevated risk of mental ill health. Caregivers in remote areas with limited access to shops and services were also at a significantly increased risk as evidenced by prescription rates for antidepressants. With community care policies aimed at supporting people to remain at home, the paper highlights the need for further research in order to target resources appropriately.

The influence of socio-demographic, psychological and knowledge-related variables alongside perceived cooking and food skills abilities in the prediction of diet quality in adults: a nationally representative cross-sectional study

Background: Interventions to increase cooking skills (CS) and food skills (FS) as a route to improving overall diet are popular within public health. This study tested a comprehensive model of diet quality by assessing the influence of socio-demographic, knowledge- and psychological-related variables alongside perceived CS and FS abilities. The correspondence of two measures of diet quality further validated the Eating Choices Index (ECI) for use in quantitative research.
Methods: A cross-sectional survey was conducted in a quota-controlled nationally representative sample of 1049 adults aged 20–60 years drawn from the Island of Ireland. Surveys were administered in participants’ homes via computer-assisted personal interviewing (CAPI) assessing a range of socio-demographic, knowledge- and psychological-related variables alongside perceived CS and FS abilities. Regression models were used to model factors influencing diet quality. Correspondence between 2 measures of diet quality was assessed using chi-square and Pearson correlations.
Results: ECI score was significantly negatively correlated with DINE Fat intake (r = -0.24, p < 0.001), and ECI score was significantly positively correlated with DINE Fibre intake (r = 0.38, p < 0.001), demonstrating a high agreement. Findings indicated that males, younger respondents and those with no/few educational qualifications scored significantly lower on both CS and FS abilities. The relative influence of socio-demographic, knowledge, psychological variables and CS and FS abilities on dietary outcomes varied, with regression models explaining 10–20 % of diet quality variance. CS ability exerted the strongest relationship with saturated fat intake (β = -0.296, p < 0.001) and was a significant predictor of fibre intake (β = -0.113, p < 0.05), although not for healthy food choices (ECI) (β = 0.04, p > 0.05).
Conclusion: Greater CS and FS abilities may not lead directly to healthier dietary choices given the myriad of other factors implicated; however, CS appear to have differential influences on aspects of the diet, most notably in relation to lowering saturated fat intake. Findings suggest that CS and FS should not be singular targets of interventions designed to improve diet; but targeting specific sub-groups of the population e.g. males, younger adults, those with limited education might be more fruitful. A greater understanding of the interaction of factors influencing cooking and food practices within the home is needed.

Sub-fossil Insects and ecosystem dynamics in wetlands; implications for biodiversity and conservation.

We review the uses of fossil insects, particularly Coleoptera (beetles) and Chironomidae (non-biting midges) from ancient deposits to inform the study of wetland ecosystems and their ecological and restoration processes. In particular, we focus on two contrasting ecosystems, drawing upon research undertaken by us on British raised mire peats and shallow lake systems, one an essentially terrestrial ecosystem, the other aquatic, but in which wetland insects play an important and integral part. The study of raised mire peats suggests that faunal stability is a characteristic of these wetland systems, over what appear to be extensive periods of time (up to several millennia), whilst studies of shallow lake ecosystems over recent timescales indicates that faunal instability appears to be more common, usually driven by increasing eutrophication. Drawing upon a series of fossil Coleoptera records spanning several thousand years from Hatfield Moors, south Yorkshire, we reconstruct in some detail the mire’s ontogeny and fluctuations in site hydrology and vegetation cover, illustrating the intimate association between substrate, topography and peat development. A comparison between fossil and modern beetle populations indicates that the faunal characteristics of this mire and its adjacent neighbour, Thorne Moors, become established during the early phases of peat development, including its rare endemics, and that the faunal biodiversity on the sites today is dictated by complex site histories. The over-riding characteristic of these faunas is of stability over several thousand years, which has important implications for the restoration of degraded sites, especially those where refugial areas are limited. In contrast, analyses of fossil Chironomidae from shallow lakes allow researchers to track changes in limnological status and while attempts have been made to reconstruct changes in nutrient levels quantitatively, the chironomids respond indirectly to such changes, typically mediated through complex ecosystem dynamics such as changes in fish and/or macrophyte communities. These changes are illustrated via historic chironomid stratigraphies and diversity indices from a range of shallow lakes located across Britain: Slapton Ley, Frensham Great Pond, Fleet Pond, Kyre Pool and Barnes Loch. These sites have shown varying degrees of eutrophication over recent timescales which tends to be associated with a decline in chironomid diversity. While complex functional processes exist within these ecosystems, our evidence suggests that one of the key drivers in the loss of shallow lake chironomid diversity appears to be the loss of aquatic macrophytes. Overall, while chironomids do show a clear response to altered nutrient regimes, multi-proxy reconstructions are recommended for a clear interpretation of past change. We conclude that if we are to have a better understanding of biota at the ecosystem level we need to know more of the complex interactions between different insect groups as well as with other animal and plant communities. A palaeoecological approach is thus crucial in order to assess the role of insect groups in ecosystem processes, both in the recent past and over long time scales, and is essential for wetland managers and conservation organisations involved in long term management and restoration of wetland systems.

International order flows: Explaining equity and exchange rate returns

Macroeconomic models of equity and exchange rate returns perform poorly at high frequencies. The proportion of daily returns that these models explain is essentially zero. Instead of relying on macroeconomic determinants, we model equity price and exchange rate behavior based on a concept from microstructure – order flow. The international order flows are derived from belief changes of different investor groups in a two-country setting. We obtain a structural relationship between equity returns, exchange rate returns and their relationship to home and foreign equity market order flow. To test the model we construct daily aggregate order flow data from 800 million equity trades in the U.S. and France from 1999 to 2003. Almost 60% of the daily returns in the S&P100 index are explained jointly by exchange rate returns and aggregate order flows in both markets. As predicted by the model, daily exchange rate returns and order flow into the French market have significant incremental explanatory power for the daily S&P returns. The model implications are also validated for intraday returns.

Law and Society: Volume III: Legal Processes and Professional Groups within the Legal Field

The thriving and well-established field of Law and Society (also referred to as Socio-legal Studies) has diverse methodological influences; it draws on social-scientific and arts-based methods. The approach of scholars researching and teaching in the field often crosses disciplinary borders, but, broadly speaking, Law and Society scholarship goes behind formalism to investigate how and why law operates, or does not operate as intended, in society. By exploring law’s connections with broader social and political forces—both domestic and international—scholars gain valuable perspectives on ideology, culture, identity, and social life. Law and Society scholarship considers both the law in contexts, as well as contexts in law.
Law and Society flourishes today, perhaps as never before. Academic thinkers toil both on the mundane and the local, as well as the global, making major advances in the ways in which we think both about law and society. Especially over the last four decades, scholarly output has rapidly burgeoned, and this new title from Routledge’s acclaimed Critical Concepts in Law series answers the need for an authoritative reference collection to help users make sense of the daunting quantity of serious research and thinking.
Edited by the leading scholars in the field, Law and Society brings together in four volumes the vital classic and contemporary contributions. Volume I is dedicated to historical antecedents and precursors. The second volume covers methodologies and crucial themes. The third volume assembles key works on legal processes and professional groups, while the final volume of the collection focuses on substantive areas. Together, the volumes provide a one-stop ‘mini library’ enabling all interested researchers, teachers, and students to explore the origins of this thriving sub discipline, and to gain a thorough understanding of where it is today.

Photobactericidal effects of TiO 2 thin films at low temperatures - A preliminary study

The efficacy of TiO ₂ photocatalysis for the destruction of pathogenic bacteria has been demonstrated by a number of groups over the past two decades. Pathogenic bacteria represent a significant hazard for the food and drink industry. Current practices in this industry dictate that rigorous sanitizing regimes must be regularly implemented resulting in lost production time. The incorporation of a TiO ₂ antibacterial surface coating in this setting would be highly desirable. In this paper we report a preliminary study of the efficacy of a TiO ₂ coating, doped with the lanthanide, neodymium, at low temperature conditions such as those utilised in the food and drink sector. The rapid destruction of Staphylococcus aureus, a common foodborne pathogen, was observed using TiO ₂ films coated to glass and steel substrates.