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Multispectral graphene-based electro-optical surfaces with reversible tunability from visible to microwave wavelengths
No full textOptical materials with colour changing abilities have been explored for use in display devices 1, smart windows 2,3 or in the modulation of visual appearance 4–6. The efficiency of these materials, however, has strong wavelength dependence, which limits their functionality to a specific spectral range. Here, we report graphene-based electro-optical devices with unprecedented optical tunability covering the entire electromagnetic spectrum from the visible to microwave. We achieve this non-volatile and reversible tunability by electro-intercalation of lithium into graphene layers in an optically accessible device structure. The unique colour changing capability, together with area-selective intercalation, inspires the fabrication of new multispectral devices, including display devices and electro-optical camouflage coating. We anticipate that these results provide realistic approaches for programmable smart optical surfaces with a potential utility in many scientific and engineering fields such as active plasmonics and adaptive thermal management. </p
Glutarate hydroxylation by the carbon starvation-induced protein D. A computational study into the stereo- and regioselectivity of the re-action.
No full textThe carbon starvation-induced protein D (CsiD) is a recently characterized iron(II)/α-ketoglutarate-dependent oxygenase that activates a glutarate molecule as substrate at the C2 position to exclusively produce (S)-2-hydrox-yglutarate products. This selective hydroxylation reaction by CsiD is an important component of the lysine biodegradation pathway in Escherichia coli; however, little is known on the details and the origin of the selectivity of the reaction. So far, experimental studies failed to trap and characterize any short-lived catalytic cycle intermediates. As no computational studies have been reported on this enzyme either, we decided to investigate the chemical reaction mechanism of glutarate activation by an iron(IV)-oxo model of the CsiD enzyme. In this work, we present a density functional theory study on a large active site cluster model of CsiD and investigate the glutarate hydroxylation pathways by a high-valent iron(IV)-oxo species leading to (S)-2–hydroxyglutarate, (R)-2-hydroxyglutarate and 3-hydroxyglutarate. In agreement with experimental observation, the favorable product channel leads to pro-S C2H hydrogen atom abstraction to form (S)-2-hydroxyglutarate. The reaction is stepwise with a hydrogen atom abstraction by an iron(IV)-oxo species followed by OH rebound from a radical intermediate. The work presented in this paper shows that despite the fact that the CH bond strengths at the C2 and C3 positions of glutarate are similar in the gas-phase, substrate binding and positioning guides the reaction to an enan-tioselective reaction process by destabilizing the hydrogen atom abstraction pathways for the pro-R C2H and C3H posi-tions. Our studies predict the chemical properties of the iron(IV)-oxo species, and its rate-constants with glutarate substrate and its deuterated form. Moreover, the work shows little protein motions during the catalytic process, while substrate entrance into the substrate binding pocket appears to be guided by three active site arginine residues that position the substrate for pro-S C2H hydrogen atom abstraction
REiNS: Genotype-Phenotype correlations in neurofibromatosis and their potential clinical use
No full textObjective: As clinically validated biomarkers for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2), have not been identified to date, we wanted to determine whether genotype-phenotype correlations are usefull in clinical trials in Neurofibromatosis 1 and 2 Methods: The biomarker group first performed a systematic literature search and reviewed existing data on genetic biomarkers in NF1 and NF2 and in in malignant peripheral nerve sheath tumours (MPNST). The group then met during a series of consensus meetings to develop a jointreport.Results: We found that In NF2 the genetic severity score is clearly of potential clinical use. In NF1despite over 3000 constitutional variants having been described in the NF1 gene, only four actionable genotype phenotype correlations currently exist. The diagnosis and treatment decision of these tumours should ideally include histopathology and compilation of some of the genetic markersConclusion: We summarized emerging clinical use of genotype-phenotype correlations in Neurofibromatosis
Baseline Interleukin-6 and 8 Predict Response and Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib Monotherapy:An Exploratory Post-hoc Analysis of the SORAMIC Trial
No full textPurpose To explore the potential correlation between baseline interleukin (IL) values and overall survival or objective response in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Methods A subset of patients with HCC undergoing sorafenib monotherapy within a prospective multicenter phase II trial (SORAMIC, sorafenib treatment alone vs. combined with Y90 radioembolization) underwent baseline IL-6 and IL-8 assessment before treatment initiation. In this exploratory post-hoc analysis, the best cut-off points for baseline IL-6 and IL-8 values predicting overall survival (OS) were evaluated, as well as correlation with the objective response. Results Forty-seven patients (43 male) with a median OS of 13.8 months were analyzed. Cut-off values of 8.58 and 57.9 pg/mL most effectively predicted overall survival for IL-6 and IL-8, respectively. Patients with high IL-6 (HR, 4.1 [1.9-8.9], p<0.001) and IL-8 (HR, 2.4 [1.2-4.7], p=0.009) had significantly shorter overall survival than patients with low IL values. Multivariate analysis confirmed IL-6 (HR, 2.99 [1.22-7.3], p=0.017) and IL-8 (HR, 2.19 [1.02-4.7], p=0.044) as independent predictors of OS. Baseline IL-6 and IL-8 with respective cut-off values predicted objective response rates according to mRECIST in a subset of 42 patients with follow-up imaging available (IL-6, 46.6% vs. 19.2%, p=0.007; IL-8, 50.0% vs. 17.4%, p=0.011). Conclusion IL-6 and IL-8 baseline values predicted outcomes of sorafenib-treated patients in this well-characterized prospective cohort of the SORAMIC-trial. We suggest that the respective cut-off values might serve for validation in larger cohorts, potentially offering guidance for improved patient selection
Cost–effective Variational Active Entity Resolution
No full textAccurately identifying different representations of the same real–world entity is an integral part of data cleaning and many methods have been proposed to accomplish it. The challenges of this entity resolution task that demand so much research attention are often rooted in the task–specificity and user–dependence of the process. Adopting deep learning techniques has the potential to lessen these challenges. In this paper, we set out to devise an entity resolution method that builds on the robustness conferred by deep autoencoders to reduce human–involvementcosts. Specifically, we reduce the cost of training deep entity resolution models by performing unsupervised representation learning. This unveils a transferability property of the resulting model that can further reduce the cost of applying the approach to new datasets by means of transfer learning. Finally, we reduce the cost of labeling training data through an active learning approach that builds on the properties conferred by the use of deep autoencoders. Empirical evaluation confirms the accomplishment of our cost–reduction desideratum, while achieving comparableeffectiveness with state–of–the–art alternatives
Diagnosing pulmonary aspergillosis is much easier than it used to be: A new diagnostic landscape
No full textSignificant innovations in the past decade have resulted in more sensitive and faster diagnosis of allergic, chronic and invasive pulmonary aspergillosis, as well as Aspergillus bronchitis and Aspergillus nodules. This new diagnostic landscape has revealed that the incidence and prevalence of aspergillosis is substantially higher than previously understood. Oral and intravenous antifungal therapy offers good clinical response rates for affected patients. Yet, missed diagnosis leaves patients over-treated with antibacterial agents, corticosteroids and anti-tuberculous drugs resulting in continuing illness and often death. The clinical introduction of several high performing diagnostic tests is helping to redefine patient management. Assuredly, Aspergillus antigen can be detected in 70-95% of bronchoscopy samples in patients with invasive and chronic aspergillosis in less than 1 hour. Aspergillus IgG (precipitins) is >90% sensitive and 98% specific for chronic and allergic aspergillosis. High volume respiratory fungal culture and Aspergillus PCR have 3-5 fold much higher sensitivity than routine bacterial culture. Aspergillus IgE (or skin prick testing) diagnoses Aspergillus sensitisation in asthma, cystic fibrosis, COPD and after TB, and correlates well with poorer lung function and/or exacerbations. Across the world, clinicians and laboratorians need to mainstream these excellent new tools to improve clinical outcomes by delivering results in a more timely and accurate fashion
Disrupting transitions: qualitatively modelling the impact of Covid-19 on UK food and mobility provision
No full textThe 2020 Covid-19 pandemic provides an empirical testing ground for assessing the impact of critical events on societal transitions. Such events are typically seen as exogenous to the transition process, an assumption which is investigated in this paper. Using a qualitative system dynamics modelling approach we conceptualize transition pathways as sets of interacting sequences of events. This enables the analysis of event sequences that constitute the evolving pandemic as impacting on those pathways. We apply this approach to the provision of (auto)mobility and food in the UK. This shows the way in which the pandemic has had a differential effect on ongoing transitions in both systems, sometimes slowing them down, and sometimes accelerating them. In addition, it reveals how it has established new transition pathways. The empirical work further shows how qualitative modelling with system dynamics facilitates an explicit a systematic comparative analysis of transition case studies
The efficacy of interactive group psychoeducation for children with leukaemia: A randomised controlled trial
No full textObjective To evaluate an interactive group psychoeducation programme for children treated for leukaemia. Methods A longitudinal randomised controlled study across four UK hospitals with an immediate (N=26) and delay control group (N=32). The intervention covered the pathophysiology of leukaemia, its treatment, side effects and the importance of positive health behaviours. Primary outcomes were parent-reported child health related quality of life (HRQoL) and behavioural difficulties. Secondary outcomes were child-reported HRQoL, cancer-specific HRQoL, child confidence, caregiver burden, and treatment anxiety. Measures were completed pre- and immediately post-intervention, and at 13 and 26-weeks follow-up. Change over time was analysed using multilevel modelling. Acceptability questionnaires rated the intervention on benefits, recommendations, and barriers to participation. Results The intervention significantly improved parent-reported child HRQoL but did not have a significant effect on other outcomes. Acceptability of the intervention was high. Conclusions This study provides initial evidence that interactive group psychoeducation is acceptable to families and improves HRQoL in children with leukaemia. Difficulties with recruitment removed power to detect effect sizes that are plausible for psychoeducational interventions. Practise implications Further studies to explore the potential of psychoeducation to improve outcomes for children with leukaemia and an examination of barriers to participation within this population are warranted
