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Nanoscale Mapping of the Conductivity and Interfacial Capacitance of an Electrolyte Gated Organic Field Effect Transistor under Operation
No full textProbing nanoscale electrical properties of organic semiconducting materials at the interface with an electrolyte solution under external applied voltages is key in the field of organic bioelectronics. It is demonstrated that the conductivity and interfacial capacitance of the active channel of an Electrolyte Gated Organic Field Effect Transistor (EGOFET) under operation can be probed at the nanoscale using Scanning Dielectric Microscopy in force detection mode in liquid environment. Local electrostatic force vs gate voltage transfer characteristics at each point on the device are obtained and correlated with the global current-voltage transfer characteristics of the EGOFET. The nanoscale maps of the conductivity of the semiconducting channel shows the dependence of the channel conductivity on the gate voltage and its variation along the channel due to the space charge limited conduction. The maps reveal very small electrical heterogeneities, which correspond to local interfacial capacitance variations due to an ultrathin non-uniform insulating layer resulting from a phase separation in the organic semiconducting blend. Present results offer insights on the transduction mechanism at the organic semiconductor/electrolyte interfaces at scales down to ~100nm, which can bring substantial optimization of organic electronic devices for bioelectronic applications such as electrical recording on excitable cells or label-free biosensing
A phase Ib study of NUC-1031 in combination with cisplatin for the first-line treatment of patients with advanced biliary tract cancer (ABC-08)
No full textBackground: Cisplatin/gemcitabine is standard 1st-line treatment for patients with advanced biliary tract cancer (ABC). NUC-1031 (phosphoramidate transformation of gemcitabine) is designed to enhance efficacy by maximising intra-tumoural active metabolites. Methods: Patients with untreated ABC, ECOG-PS 0-1 received NUC-1031 (625 or 725mg/m2) and cisplatin (25mg/m2) on days 1 and 8, every 21 days. Objectives: safety and maximum tolerated dose (primary); and ORR, pharmacokinetics, PFS and OS (secondary). Results: Twenty-one patients (median age 61 years, n=13 male; 17 cholangiocarcinoma, 2 ampullary and 2 gallbladder cancer) received NUC-1031 625mg/m2 (n=8 and expansion n=7; median 6 cycles) or 725mg/m2 (n=6; median 7.5 cycles). Treatment was well tolerated; most common treatment-emergent grade 3-4 adverse-events occurring in >1 patient with 625mg/m2 NUC-1031 were increased GGT: 40%, ALT: 20%, bilirubin: 13%, neutropenia: 27%, decreased WCC: 20%, thrombocytopenia: 13%, nausea: 13%, diarrhea: 13%, fatigue: 13%, and thrombus: 20% and with 725mg/m2, increased GGT: 67% and fatigue: 33%. NUC-1031 725mg/m2 was selected as the recommended dose with cisplatin in ABC. ORR: 33% (1 CR, 6 PRs), DCR 76%, median PFS 7.2 months (95%-CI 4.3-10.1), median OS 9.6 months (95%-CI 6.7-13.1). The median plasma AUC0-24 and Cmax estimates were highest for NUC-1031 (218-324 μg•h/mL and 309-889 μg/mL, respectively) and lowest for dFdC (0.47-1.56 μg•h/mL and 0.284-0.522 μg/mL, respectively). Conclusions: This is the first study reporting on the combination of NUC-1031 with cisplatin in ABC and demonstrated a favourable safety profile; 725mg/m2 NUC-1031 in combination with cisplatin is undergoing phase III trial evaluation in ABC
HPB cancers in older patients:Inclusion of elderly patients in clinical trials
No full textLiver, biliary tract and pancreatic cancers are increasingly diseases of older people and the global population is aging. ‘The elderly’ are heterogeneous group who vary widely in their general health, physical reserve and degree of dependence on others. Cancer is not the only disease that becomes more prevalent in old age, which means elderly patients may also have comorbidities and lower resilience. The use of chemotherapy decreases as age increases. Chemotherapy treatment regimens may require modification to reduce toxicity, which is more common in elderly patients. The effect this has on treatment efficacy is not fully understood.Elderly patients are not represented well in clinical trials which makes estimating benefit for these patients challenging. Medicine demands that new drugs are rigorously tested and evaluated before use, yet clinicians are treating elderly patients on the basis of extrapolating from randomised controlled trials which actively exclude comorbidities and older patients. This review considers the current situation and the value of retrospective analyses and real-world evidence to plug the elderly patient ‘data gaps’.Moving forwards it is essential to broaden clinical trial inclusion criteria to include more elderly people. The use of appropriate geriatric assessments may help selection of older patients who are fit enough for more rigorous regimens, alongside effective methods of predicting and managing treatment toxicities. The ability to see past the numerical age of a person and offer appropriate therapeutic choices to individual patients in clinic, is an important skill for younger (and not so young) Medical Oncologists to learn
Assessing the effect of interventions for axial spondyloarthritis according to the endorsed ASAS/OMERACT Core Outcome Set: A meta-research study of trials included in Cochrane reviews
No full textThe Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DCART). These include the following domains for all three core sets: “physical function,” “pain,” “spinal mobility,” “spinalstiffness,” and “patient’s global assessment” (PGA). The core set for clinical record keeping further includes the domains “peripheral joints/entheses” and “acute phase reactants,” and the core set for DC-ART further includes the domains “fatigue” and “spine radiographs/hip radiographs.” The Outcome Measures in Rheumatology (OMERACT)endorsed the core sets in 1998.Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to metaanalyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials.Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/ physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcomedomains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and “missing data”) should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain providea valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation
Heavy metal sensors and sequestrating agents based on polyaromatic copolymers and hydrogels
No full textA series of readily available, amphiphilic pyrene- and perylene-containing fluorescent materials, derived from the co-polymerisation of 2-acrylamido-2-methyl-1-propansulfonic acid (AMPS) with acrylate esters, can be used to detect heavy metal ions in the micromolar concentration range in aqueous solutions. The incorporation of these amphiphilic copolymers into semi-interpenetrating hydrogels also resulted in the irreversible removal of divalent Co2+, Ni2+, Cu2+ and Pb2+ ions from aqueous solutions at neutral pH
On Lyapunov-Lur'e Functional Based Stability Criterion for Discrete-Time Lur'e Systems
No full textIn this manuscript, we consider the stability problem of Lur’e systems with sloperestrictednonlinearities. We focus on a specific parametrisation of the Lyapunov-Lur’e functionalin the literature, and extend it to a higher order. Meanwhile, we show this Lyapunov-Lur’efunctional based stability criterion is equivalent to the search for noncausal FIR multiplierswith a restricted form for the SISO case. Finally, we discuss the restrictions of this Lyapunov-Lur’e functional approach with some numerical examples
Child-led research investigating social, emotional and mental health and wellbeing aspects of playtime
No full textAim: This study aimed to investigate social, emotional and mental health and wellbeing aspects of playtime through child-led participatory action research in one school.Method: A stakeholder group involving the project facilitator (first researcher), school staff and four trained child co-researchers (aged 9-10) was established to facilitate the research. The co-researchers were supported to design and facilitate data collection and collaborative thematic data analysis. Findings: Five main themes emerged from analysis: the availability and nature of games, having someone to play with, how people treat each other, the importance of playtimes and views of the playtime rules. This research highlights interactions between the themes as important to children’s social and emotional development, and mental health and wellbeing when accessing their right to play during playtime. Limitations: Research was completed on a single site. Repeating the design at another school might yield different results. While steps were taken to minimise power imbalances between the child participants and the project facilitator, it is acknowledged that these are difficult to overcome fully. Conclusions: This study highlights the importance of holistic playtime provision that acknowledges the interactions between themes in supporting children’s wellbeing and social and emotional development. It illustrates that with appropriate training and support, children were able to effectively engage in research investigating playtime.<br/
On bounds for the mode and median of the generalized hyperbolic and related distributions
No full textExcept for certain parameter values, a closed form formula for the mode of thegeneralized hyperbolic (GH) distribution is not available. In this paper, we exploitresults from the literature on modied Bessel functions and their ratios to obtainsimple but tight two-sided inequalities for the mode of the GH distribution for general parameter values. As a special case, we deduce tight two-sided inequalities for the mode of the variance-gamma (VG) distribution, and through a similar approach we also obtain tight two-sided inequalities for the mode of the McKay Type I distribution. The analogous problem for the median is more challenging, but we conjecture some monotonicity results for the median of the VG and McKay Type I distributions, from we which we conjecture some tight two-sided inequalities for their medians. Numerical experiments support these conjectures and also lead us to a conjectured tight lower bound for the median of the GH distribution