Autobiographical memory specificity, depression, and trauma in bipolar disorder

Objectives. In a bipolar disorder (BD) sample, the present study investigated: (i) the prevalence of trauma; (ii) the specificity of autobiographical memory (AM); (iii) the influence of childhood trauma on AM specificity, current inter-episode depressive mood, and BD severity; (iv) if AM specificity moderates the influence of childhood trauma on current inter-episode depressive mood and BD severity.

Methods. Fifty-two participants were recruited from a geographically well-defined mental health service in Northern Ireland. The AM test, self-report measures of lifetime experience of trauma, childhood trauma, and depression were administered. Severity of BD was estimated utilizing a systematic tool for reviewing all available clinical data of participants.

Results. A high prevalence of trauma was found. A total of 94.2% (49/52) of participants reported experiencing a traumatic event in either childhood or adulthood. AM specificity was significantly lower than previous reports of such in major depression. However, whilst childhood trauma predicted current inter-episode depressive mood, childhood trauma was not predictive of BD severity or AM specificity. Moreover, the association between childhood trauma and depressed mood was not moderated by AM specificity.

Conclusions. The findings of this study suggest a relationship between early psychosocial adversity and current inter-episode depressive mood in BD. In addition, levels of overgeneral AM are similar to that reported for depression, but are unrelated to childhood trauma, current inter-episode depressive mood, or BD severity. Clinical implications include the importance of routine assessment of trauma in BD and the need for adjunctive evidenced-based psychological therapies.

Hydrolysis characteristics and kinetics of waste hay biomass as a potential energy crop for fermentable sugars production using autoclave parr reactor system

The use of the organic fraction of municipal solid waste crops has received considerable attention as a sustainable feedstock that can replace fossil fuels for the production of renewable energy. Therefore, municipal bin-waste in the form of hay was investigated as a potential energy crop for fermentable sugars production. Hydrolysis of hay by dilute phosphoric acid was carried out in autoclave parr reactor, where reactor temperature (135-200 degrees c) and acid concentration (2.5-10% (w/w)) were examined. Analysis of the decomposition rate of hemicellulosic biomass was undertaken using HPLC of the reaction products. Xylose production reached a maximum value of 13.5 g/100 g dry mass corresponding to a yield of 67% at the best identified conditions of 2.5 wt% H3PO4, 175 degrees C, 10 min reaction time, and at 5 wt% H3PO4, 150 degrees C, and 5 min reaction time. For glucose, an average yield of 25% was obtained at 5 wt% H3PO4, 175 degrees C and 30 min. Glucose degradation to HMF was achieved at 10 wt% H3PO4 and 200 degrees C. The maximum yield for produced arabinose was an average of 3 g/100 g dry. mass corresponding to 100% of the total possible arabinose. The kinetic study of the acid hydrolysis was also carried out using the Saeman and the Two-fraction models. It was found for both models that the kinetic constants (k) depend on the acid concentration and temperature. For xylose and arabinose it was found that the rate of formation was more favoured than the rate of degradation. By contrast, for glucose it was found that glucose degradation was occurring faster than glucose formation. It can be concluded that dilute phosphoric acid hydrolysis of hay crop is feasible for the production of fermentable sugars which are essential for bioethanol synthesis. 

Dilute phosphoric acid-catalysed hydrolysis of municipal bio-waste wood shavings using autoclave parr reactor system

The visibility of using municipal bio-waste, wood shavings, as a potential feedstock for ethanol production was investigated. Dilute acid hydrolysis of wood shavings with H3PO4 was undertaken in autoclave parr reactor. A combined severity factor (CSF) was used to integrate the effects of hydrolysis times, temperature and acid concentration into a single variable. Xylose concentration reached a maximum value of 17 g/100 g dry mass corresponding to a yield of 100% at the best identified conditions of 2.5 wt.% H3PO4, 175 degrees C and 10 min reaction time corresponding to a CSF of 1.9. However, for glucose, an average yield of 30% was obtained at 5 wt.% H3PO4, 200 degrees C and 10 min. Xylose production increased with increasing temperature and acid concentration, but its transformation to the degradation product furfural was also catalysed by those factors. The maximum furfural formed was 3 g/100 g dry mass, corresponding to the 24% yield. (C) 2011 Elsevier Ltd. All rights reserved.

JAK2V617F homozygosity arises commonly and recurrently in PV and ET, but PV is characterized by expansion of a dominant homozygous subclone

Subclones homozygous for JAK2V617F are more common in polycythemia vera (PV) than essential thrombocythemia (ET), but their prevalence and significance remain unclear. The JAK2 mutation status of 6495 BFU-E, grown in low erythropoietin conditions, was determined in 77 patients with PV or ET. Homozygous-mutant colonies were common in patients with JAK2V617F-positive PV and were surprisingly prevalent in JAK2V617F-positive ET and JAK2 exon 12-mutated PV. Using microsatellite PCR to map loss-of-heterozygosity breakpoints within individual colonies, we demonstrate that recurrent acquisition of JAK2V617F homozygosity occurs frequently in both PV and ET. PV was distinguished from ET by expansion of a dominant homozygous subclone, the selective advantage of which is likely to reflect additional genetic or epigenetic lesions. Our results suggest a model in which development of a dominant JAK2V617F-homzygous subclone drives erythrocytosis in many PV patients, with alternative mechanisms operating in those with small or undetectable homozygous-mutant clones.

Fermentable sugars recovery from lignocellulosic waste-newspaper by catalytic hydrolysis

The urgent need for alternative renewable energies to supplement petroleum-based fuels and the reduction of landfill sites for disposal of solid wastes makes it increasingly attractive to produce inexpensive biofuels from the organic fraction of the municipal solid waste. Therefore, municipal waste in the form of newspaper was investigated as a potential feedstock for fermentable sugars production. Hydrolysis of newspaper by dilute phosphoric acid was carried out in autoclave Parr reactor, where reactor temperature and acid concentration were examined. Xylose concentration reached a maximum value of 14 g/100 g dry mass corresponding to a yield of 94% at the best identified conditions of 2.5 wt% HPO, 135°C, 120 min reaction time, and at 2.5 wt% HPO, 150°C, and 60 min reaction time. For glucose, an average yield of 26% was obtained at 2.5 wt% HPO, 200°C, and 30 min. Furfural and 5-hydroxymethylfurfural (HMF) formation was clearly affected by reaction temperature, where the higher the temperature the higher the formation rate. The maximum furfural formed was an average of 3 g/100 g dry mass, corresponding to a yield of 28%. The kinetic study of the acid hydrolysis was also carried out using the Saeman and the two-fraction models. It was found for both models that the kinetic constants (K) depend on the acid concentration and temperature. The degradation of HMF to levulinic acid is faster than the degradation of furfural to formic acid. Also, the degradation rate is higher than the formation rate for both inhibitors when degradation is observed.

Neutral Genomic Microevolution of a Recently Emerged Pathogen, Salmonella enterica Serovar Agona

Salmonella enterica serovar Agona has caused multiple food-borne outbreaks of gastroenteritis since it was first isolated in 1952. We analyzed the genomes of 73 isolates from global sources, comparing five distinct outbreaks with sporadic infections as well as food contamination and the environment. Agona consists of three lineages with minimal mutational diversity: only 846 single nucleotide polymorphisms (SNPs) have accumulated in the non-repetitive, core genome since Agona evolved in 1932 and subsequently underwent a major population expansion in the 1960s. Homologous recombination with other serovars of S. enterica imported 42 recombinational tracts (360 kb) in 5/143 nodes within the genealogy, which resulted in 3,164 additional SNPs. In contrast to this paucity of genetic diversity, Agona is highly diverse according to pulsed-field gel electrophoresis (PFGE), which is used to assign isolates to outbreaks. PFGE diversity reflects a highly dynamic accessory genome associated with the gain or loss (indels) of 51 bacteriophages, 10 plasmids, and 6 integrative conjugational elements (ICE/IMEs), but did not correlate uniquely with outbreaks. Unlike the core genome, indels occurred repeatedly in independent nodes (homoplasies), resulting in inaccurate PFGE genealogies. The accessory genome contained only few cargo genes relevant to infection, other than antibiotic resistance. Thus, most of the genetic diversity within this recently emerged pathogen reflects changes in the accessory genome, or is due to recombination, but these changes seemed to reflect neutral processes rather than Darwinian selection. Each outbreak was caused by an independent clade, without universal, outbreak-associated genomic features, and none of the variable genes in the pan-genome seemed to be associated with an ability to cause outbreaks. © 2013 Achtman et al

Realist evaluation - promise, problems and practicalities

Realist evaluation is an innovative, multi-method approach to evaluating the effectiveness of complex health care interventions that is having an increasing impact on the research community. Drawing on their experience doing four realist evaluations in diverse areas of healthcare, the authors offer a comprehensive overview and critique of essential theory and practice. The first paper (Realist review and realist evaluation: an introduction) introduces the main components of the approach and shows how realist review can support realist evaluation. The second paper (Concepts and methodology for realist evaluation: help or hindrance?) provides further detail on the key concepts, shows how they can be operationalised, and discusses the advantages and difficulties of using these ideas. Following these two papers introducing and illustrating the major concepts, the third paper (Realist Evaluation: a critical realist critique) takes a step back to re-consider realist evaluation in relation to its critical realist roots, asking whether it leads to evaluators abandoning the attempt to understand (and if necessary challenge) the underlying values of health care interventions and contenting themselves merely with explicating the factors that help or hinder implementation. The fourth and final paper (Data analysis and theory development in realist evaluation) plunges back into the tangled undergrowth of multiple-method data collection and shows how disparate forms of data can be synthesised for theory development, and the results presented in a form that is useful to practitioners and policy-makers.

Evaluating Many Treatments and Biomarkers in Oncology: A New Design

There is a pressing need for more-efficient trial designs for biomarker-stratified clinical trials. We suggest a new approach to trial design that links novel treatment evaluation with the concurrent evaluation of a biomarker within a confirmatory phase II/III trial setting. We describe a new protocol using this approach in advanced colorectal cancer called FOCUS4. The protocol will ultimately answer three research questions for a number of treatments and biomarkers: (1) After a period of first-line chemotherapy, do targeted novel therapies provide signals of activity in different biomarker-defined populations? (2) If so, do these definitively improve outcomes? (3) Is evidence of activity restricted to the biomarker-defined groups? The protocol randomizes novel agents against placebo concurrently across a number of different biomarker-defined population-enriched cohorts: BRAF mutation; activated AKT pathway: PI3K mutation/absolute PTEN loss tumors; KRAS and NRAS mutations; and wild type at all the mentioned genes. Within each biomarker-defined population, the trial uses a multistaged approach with flexibility to adapt in response to planned interim analyses for lack of activity. FOCUS4 is the first test of a protocol that assigns all patients with metastatic colorectal cancer to one of a number of parallel population-enriched, biomarker-stratified randomized trials. Using this approach allows questions regarding efficacy and safety of multiple novel therapies to be answered in a relatively quick and efficient manner, while also allowing for the assessment of biomarkers to help target treatment.

General practitioners’ management of the long-term sick role

In this paper, we use qualitative research techniques to examine the role of general practitioners in the management of the long-term sickness absence. In order to uncover the perspectives of all the main agents affected by the actions of general practitioners, a case study approach focussing on one particular employment sector, the public health service, is adopted. The role of family physicians is viewed from the perspectives of health service managers, occupational health physicians, employees / patients, and general practitioners. Our argument is theoretically framed by Talcott Parsons’s model of the medical contribution to the sick role, along with subsequent conceptualisations of the social role and position of physicians. Sixty one semi-structured interviews and three focus group interviews were conducted in three Health and Social Care Trusts in Northern Ireland between 2010 and 2012. There was a consensus among respondents that general practitioners put far more weight on the preferences and needs of their patients than they did on the requirements of employing organisations. This was explained by respondents in terms of the propinquity and longevity of relationships between doctors and their patients, and by the ideology of holistic care and patient advocacy that general practitioners viewed as providing the foundations of their approach to patients. The approach of general practitioners was viewed negatively by managers and occupational health physicians, and more positively by general practitioners and patients. However, there is some evidence that general practitioners would be prepared to forfeit their role as validators of sick leave. Given the imperatives of both state and capital to reduce the financial burden of long-term sickness, this preparedness puts into doubt the continued role of general practitioners as gatekeepers to legitimate long-term sickness absence.

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy.

Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681.

Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]).

Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials.

The role of adiposity in cardiometabolic traits:a Mendelian randomization analysis

The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.

Trajectories of Learning Dispositions and Attitudes in Upper Primary Schools in Northern Ireland: What exactly is going on?

There is increasing research and policy interest in the importance of attitudes to learning, learning orientations and learning dispositions (however they are labelled), not only because they influence traditional measures of school achievement but also because they facilitate how well children function at school, with implications for their future learning. This paper reports the findings on pupils’ learning dispositions and attitudes from two separate cohorts of pupils as they progress through upper primary school (Key Stage 2) in 50 schools in Northern Ireland. (These data are drawn from two different longitudinal studies and the data collection period predates the introduction of the new Northern Ireland Curriculum.) Approximately 1200 pupils completed seven scales from the Assessment of Learner-Centred Practices, ALCPs (McCombs and Lauer, 1997) at three time points, at the end of P5 (9 year olds), at the end of P6 (10 years olds) and at the end of P7 (11 year olds). ALCPs draws on an extensive research base that has identified cognitive and motivational dispositions and attitudes that are associated with a positive orientation to learning, and ultimately with positive progress in school (Alexander and Murphy, 1998). Although each scale can be considered separately, the seven scales cluster into two groups: self-efficacy, mastery orientation, active learning strategies and curiosity are all predicted to be pro-learning; and challenge avoidance, work avoidance, and – to a lesser extent – performance orientation, are predicted to be negatively associated with learning. The general trajectory in the children’s self-evaluations shows that they are becoming less pro-learning over time, with significant decreases in their self-ratings of active learning, curiosity, mastery orientation and self-efficacy. At the same time, there is some evidence that they work harder and put more effort into their work but this is not accompanied by maintaining their previous pro-learning motivations and strategies. The pattern is consistently more negative for boys than for girls. There are very few differences between the two cohorts indicating that the pattern is not confined to a specific cohort. These findings are challenging and will be interrogated with regard to two questions – are the changes related to the influence of the children’s school experiences per se or are they more related to developmental differences as children adopt more critical appraisals of their personal attributes and efforts as they get older? Whatever the reason, these learning dispositions and attitudes are important as they contribute significantly to school achievement even when the more traditional predictors like gender and ability are taken into account.