Gladstone and Scott: Family, identity, and nation

In the 175 years since his death, Walter Scott has regularly been hailed as an influence by politicians. Amongst the poet-novelist's nineteenth-century political admirers, William Ewart Gladstone was possibly the most ardent, genuine, and significant. Scott's poems and novels were amongst the earliest texts Gladstone read; he read no works (in English), except the Bible, so consistently or completely over such a length of time. They offered him a plethora of inspirations, ideas, and language, which he imbibed and appropriated into his public and private lives. His concept of self, his understanding of family, and his sense of home, were all forged and conducted within a Scottian frame of reference. Scott's life and works also crucially influenced Gladstone's political understanding of the Scottish nation and its people, and his conception of how he could best serve their political interests. This article casts new light on an important and influential relationship in Gladstone's life, establishing that it was neither the superficial and recreational association some have described, nor simply a ploy of an astute politician. The article falls into three parts. The first elucidates how Gladstone's consumption of Scott's writings was seminal in the formation of his private identity, both individual and familial. The second explains how Gladstone's readings of Scott fitted into the specific and serious character of his other reading and knowledge-gathering, and the third shows how the details of Gladstone's response to Scott related to the broader intellectual and cultural context of his public life. By placing Gladstone within his Scottish context, this article shows how frequently and significantly his private and public worlds intersected

Quantifying the role and value of chemical looping combustion in future electricity systems via a retrosynthetic approach

Carbon capture and sequestration of CO2 from the combustion of fossil fuels in thermal power plants is expected to be important in the mitigation of climate change. Deployment however falls far short of what is required. A key barrier is the perception by developers and investors that these technologies are too inefficient, expensive and risky. To address these issues, we have developed a novel retrosynthetic approach to evaluate technologies and their design based on the demands of the system in which they would operate. We have applied it to chemical looping combustion (CLC), a promising technology, which enables carbon dioxide emissions to be inherently captured from the combustion of fossil fuels. Our approach has provided unique insight into the potential role and value of different CLC variants in future electricity systems and the likely impact of their integration on the optimal capacity mix, the operational and system cost, and dispatch patterns. The three variants investigated could all provide significant value by reducing the total investment and operational cost of a future electricity system. The minimisation of capital cost appears to be key for the attractiveness of CLC, rather than other factors such as higher efficiency or lower oxygen carrier costs

Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

Copyright @ 2012 Nature Publishing GroupThis article has been made available through the Brunel Open Access Publishing Fund.Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity.This work was supported in part by The Vidal Sassoon Foundation USA. This article is made available through the Brunel Open Access Publishing Fund

Automaticity in the Recognition of Nonverbal Emotional Vocalizations

The ability to perceive the emotions of others is crucial for everyday social interactions. Important aspects of visual socioemotional processing, such as the recognition of facial expressions, are known to depend on largely automatic mechanisms. However, whether and how properties of automaticity extend to the auditory domain remains poorly understood. Here we ask if nonverbal auditory emotion recognition is a controlled deliberate or an automatic efficient process, using vocalizations such as laughter, crying, and screams. In a between-subjects design (N = 112), and covering eight emotions (four positive), we determined whether emotion recognition accuracy (a) is improved when participants actively deliberate about their responses (compared with when they respond as fast as possible) and (b) is impaired when they respond under low and high levels of cognitive load (concurrent task involving memorizing sequences of six or eight digits, respectively). Response latencies were also measured. Mixed-effects models revealed that recognition accuracy was high across emotions, and only minimally affected by deliberation and cognitive load; the benefits of deliberation and costs of cognitive load were significant mostly for positive emotions, notably amusement/laughter, and smaller or absent for negative ones; response latencies did not suffer under low or high cognitive load; and high recognition accuracy (approximately 90%) could be reached within 500 ms after the stimulus onset, with performance exceeding chance-level already between 300 and 360 ms. These findings indicate that key features of automaticity, namely fast and efficient/effortless processing, might be a modality-independent component of emotion recognition

High emotional contagion and empathy are associated with enhanced detection of emotional authenticity in laughter

Nonverbal vocalisations such as laughter pervade social interactions, and the ability to accurately interpret them is an important skill. Previous research has probed the general mechanisms supporting vocal emotional processing, but the factors that determine individual differences in this ability remain poorly understood. Here, we ask whether the propensity to resonate with others’ emotions—as measured by trait levels of emotional contagion and empathy—relates to the ability to perceive different types of laughter. We focus on emotional authenticity detection in spontaneous and voluntary laughs: spontaneous laughs reflect a less controlled and genuinely felt emotion, and voluntary laughs reflect a more deliberate communicative act (e.g., polite agreement). In total, 119 participants evaluated the authenticity and contagiousness of spontaneous and voluntary laughs and completed two self-report measures of resonance with others’ emotions: the Emotional Contagion Scale and the Empathic Concern scale of the Interpersonal Reactivity Index. We found that higher scores on these measures predict enhanced ability to detect laughter authenticity. We further observed that perceived contagion responses during listening to laughter significantly relate to authenticity detection. These findings suggest that resonating with others’ emotions provides a mechanism for processing complex aspects of vocal emotional information

Analysis and Computational Dissection of Molecular Signature Multiplicity

Molecular signatures are computational or mathematical models created to diagnose disease and other phenotypes and to predict clinical outcomes and response to treatment. It is widely recognized that molecular signatures constitute one of the most important translational and basic science developments enabled by recent high-throughput molecular assays. A perplexing phenomenon that characterizes high-throughput data analysis is the ubiquitous multiplicity of molecular signatures. Multiplicity is a special form of data analysis instability in which different analysis methods used on the same data, or different samples from the same population lead to different but apparently maximally predictive signatures. This phenomenon has far-reaching implications for biological discovery and development of next generation patient diagnostics and personalized treatments. Currently the causes and interpretation of signature multiplicity are unknown, and several, often contradictory, conjectures have been made to explain it. We present a formal characterization of signature multiplicity and a new efficient algorithm that offers theoretical guarantees for extracting the set of maximally predictive and non-redundant signatures independent of distribution. The new algorithm identifies exactly the set of optimal signatures in controlled experiments and yields signatures with significantly better predictivity and reproducibility than previous algorithms in human microarray gene expression datasets. Our results shed light on the causes of signature multiplicity, provide computational tools for studying it empirically and introduce a framework for in silico bioequivalence of this important new class of diagnostic and personalized medicine modalities

Protocol for the INFORMED (Individualised Patient Care and Treatment for Maternal Diabetes) Study: a randomised controlled trial embedded within routine care

Introduction Diabetes in pregnancy presents a unique physiological challenge to manage glycaemia while maintaining adequate nourishment for the growing fetus. Women with diabetes who become pregnant are at greater risk of adverse maternal and newborn outcomes, compared with women without diabetes. Evidence suggests that control of (postprandial) glycaemia is key to manage maternal and offspring health but it is not yet clear (1) how diet and lifestyle moderate these shifts across the full duration of pregnancy or (2) what aspects of maternal and offspring health are associated with dysglycaemia. Methods and analysis To investigate these gaps, a cross-over randomised clinical trial has been embedded within routine clinical care. Seventy-six pregnant women in their first trimester with type 1 or type 2 diabetes (with or without medication) attending their routine antenatal appointments at National Health Service (NHS) Leeds Teaching Hospitals will be recruited. Following informed consent, data on women’s health, glycaemia, pregnancy and delivery will be shared by the NHS with researchers. At each visit in the first (10–12 weeks), second (18–20 weeks) and third (28–34 weeks) trimester, participants will be asked for consent to: (1) lifestyle and diet questionnaires, (2) blood for research purposes and (3) analysis of urine collected at clinical visits. Additionally, participants will be asked to consume two blinded meals in duplicate in second and third trimester. Glycaemia will be assessed by continuous glucose monitoring as part of routine care. The primary outcome is the effect of experimental meals (high vs low protein) on postprandial glycaemia. Secondary outcomes include (1) the association between dysglycaemia and maternal and newborn health, and (2) the association between maternal metabolic profiles in early pregnancy with dysglycaemia in later pregnancy. Ethics and dissemination The Leeds East Research Ethics Committee and NHS (REC: 21/NE/0196) approved the study. Results will be published in peer-reviewed journals and disseminated to participants and the wider public. Trial registration number ISRCTN57579163

Nutritional and Exercise-Focused Lifestyle Interventions and Glycemic Control in Women with Diabetes in Pregnancy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Diabetes disrupts one in six pregnancies, bestowing immediate and long-term health risks to mother and child. Diet and exercise are commonly prescribed to control dysglycemia, but their effectiveness across sub-populations and types of diabetes (type-1; type-2; or gestational diabetes mellitus, GDM) is uncertain. Therefore, a systematic review and meta-analysis on the effect of diet and/or exercise on glycemia in pregnant women with diabetes was conducted. Random effects models were used to evaluate effect sizes across studies and anticipated confounders (e.g., age, ethnicity, BMI). Of the 4845 records retrieved, 26 studies (8 nutritional supplements, 12 dietary, and 6 exercise interventions) were included. All studies were conducted in patients with GDM. Overall, supplement- and exercise-based interventions reduced fasting glucose (−0.30 mmol/L; 95% CI = −0.55, −0.06; p = 0.02; and 0.10 mmol/L; 95% CI = −0.20, −0.01; p = 0.04); and supplement- and diet-based interventions reduced HOMA-IR (−0.40; 95% CI = −0.58, −0.22; p < 0.001; and −1.15; 95% CI = −2.12, −0.17; p = 0.02). Subgroup analysis by confounders only confirmed marginal changed effect sizes. Our results suggest a favorable role of certain nutritional supplements, diet, and exercise practices on glycemia in women with GDM and underline a lack of evidence in ~20% of other diabetes-related pregnancies (i.e., women with pre-existing diabetes)

General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns