Impact of adsorption on scanning electrochemical microscopy voltammetry and implications for nanogap measurements

Scanning electrochemical microscopy (SECM) is a powerful tool that enables quantitative measurements of fast electron transfer (ET) kinetics when coupled with modeling predictions from finite-element simulations. However, the advent of nanoscale and nanogap electrode geometries that have an intrinsically high surface area-to-solution volume ratio realizes the need for more rigorous data analysis procedures, as surface effects such as adsorption may play an important role. The oxidation of ferrocenylmethyl trimethylammonium (FcTMA+) at highly oriented pyrolytic graphite (HOPG) is used as a model system to demonstrate the effects of reversible reactant adsorption on the SECM response. Furthermore, the adsorption of FcTMA2+ species onto glass, which is often used to encapsulate ultramicroelectrodes employed in SECM, is also found to be important and affects the voltammetric tip response in a nanogap geometry. If a researcher is unaware of such effects (which may not be readily apparent in slow to moderate scan voltammetry) and analyzes SECM data assuming simple ET kinetics at the substrate and an inert insulator support around the tip, the result is the incorrect assignment of tip–substrate heights, kinetics, and thermodynamic parameters. Thus, SECM kinetic measurements, particularly in a nanogap configuration where the ET kinetics are often very fast (only just distinguishable from reversible), require that such effects are fully characterized. This is possible by expanding the number of experimental variables, including the voltammetric scan rate and concentration of redox species, among others

A Brief Consideration of the Later Prehistoric Appearance and Possible Significance of the Great Auk (Pinguinus impennis) in the Covesea Caves of North-East Scotland

YesThis Short Note describes the distribution and composition of the great auk assemblage found within the Covesea Caves, and discusses its significance.Glasgow Natural History Society Professor Blodwen Lloyd Binns Bequest, the Prehistoric Society, and the Society of Antiquaries of Scotland. Historic Environment Scotland and Aberdeenshire Council

User experience analysis of AbC-19 Rapid Test via lateral flow immunoassays for self-administrated SARS-CoV-2 antibody testing

Abstract Lateral flow immunoassays are low cost, rapid and highly efficacious point-of-care devices, which have been used for SARS-CoV-2 antibody testing by professionals. However, there is a lack of understanding about how self-administered tests are used by the general public for mass testing in different environmental settings. The purpose of this study was to assess the user experience (UX) (including usability) of a self-testing kit to identify COVID-19 antibodies used by a representative sample of the public in their cars, which included 1544 participants in Northern Ireland. The results based on 5-point Likert ratings from a post-test questionnaire achieved an average UX score of 96.03% [95% confidence interval (CI) 95.05–97.01%], suggesting a good degree of user experience. The results of the Wilcoxon rank sum tests suggest that UX scores were independent of the user’s age and education level although the confidence in this conclusion could be strengthened by including more participants aged younger than 18 and those with only primary or secondary education. The agreement between the test result as interpreted by the participant and the researcher was 95.85% [95% CI 94.85–96.85%], Kappa score 0.75 [95% CI 0.69–0.81] (indicating substantial agreement). Text analysis via the latent Dirichlet allocation model for the free text responses in the survey suggest that the user experience could be improved for blood-sample collection, by modifying the method of sample transfer to the test device and giving clearer instructions on how to interpret the test results. The overall findings provide an insight into the opportunities for improving the design of SARS-CoV-2 antibody testing kits to be used by the general public and therefore inform protocols for future user experience studies of point-of-care tests

Human ASPM participates in spindle organisation, spindle orientation and cytokinesis

Background Mutations in the Abnormal Spindle Microcephaly related gene (ASPM) are the commonest cause of autosomal recessive primary microcephaly (MCPH) a disorder characterised by a small brain and associated mental retardation. ASPM encodes a mitotic spindle pole associated protein. It is suggested that the MCPH phenotype arises from proliferation defects in neural progenitor cells (NPC). Results We show that ASPM is a microtubule minus end-associated protein that is recruited in a microtubule-dependent manner to the pericentriolar matrix (PCM) at the spindle poles during mitosis. ASPM siRNA reduces ASPM protein at the spindle poles in cultured U2OS cells and severely perturbs a number of aspects of mitosis, including the orientation of the mitotic spindle, the main determinant of developmental asymmetrical cell division. The majority of ASPM depleted mitotic cells fail to complete cytokinesis. In MCPH patient fibroblasts we show that a pathogenic ASPM splice site mutation results in the expression of a novel variant protein lacking a tripeptide motif, a minimal alteration that correlates with a dramatic decrease in ASPM spindle pole localisation. Moreover, expression of dominant-negative ASPM C-terminal fragments cause severe spindle assembly defects and cytokinesis failure in cultured cells. Conclusions These observations indicate that ASPM participates in spindle organisation, spindle positioning and cytokinesis in all dividing cells and that the extreme C-terminus of the protein is required for ASPM localisation and function. Our data supports the hypothesis that the MCPH phenotype caused by ASPM mutation is a consequence of mitotic aberrations during neurogenesis. We propose the effects of ASPM mutation are tolerated in somatic cells but have profound consequences for the symmetrical division of NPCs, due to the unusual morphology of these cells. This antagonises the early expansion of the progenitor pool that underpins cortical neurogenesis, causing the MCPH phenotype

High-Grade B-cell Lymphoma, Not Otherwise Specified: A Multi-Institutional Retrospective Study

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ( double hit ). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase \u3e3 × upper limit of normal, and a dual-expressor immunophenotype. Age \u3e60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS

General insurance marketing: a review and future research agenda

The financial services sector is a huge and diverse industry comprising many different forms of organisations and product offerings. Yet, a review of past papers in the Journal of Financial Services Marketing (JFSM) reveals a heavy bias towards articles on banking, to the neglect of other equally important financial services categories. The purpose of this paper is to address this imbalance and to call for more research to be conducted in a wider range of financial services categories. In particular, general insurance is singled out as a category worthy of further research. Looking to the past, this paper reviews research published to-date on general insurance in the JFSM to establish a benchmark and explore theoretical contributions. Attention is then turned to the future to identify a research agenda for the general insurance sector going forward. 5 important themes are identified: trust, transparency and simplification, technology, HNW and Takaful

Management of cutaneous metastases using electrochemotherapy

Background. Cutaneous metastases may cause considerable discomfort as a consequence of ulceration, oozing, bleeding and pain. Electrochemotherapy has proven to be highly effective in the treatment of cutaneous metastases. Electrochemotherapy utilises pulses of electricity to increase the permeability of the cell membrane and thereby augment the effect of chemotherapy. For the drug bleomycin, the effect is enhanced several hundred-fold, enabling once-only treatment. The primary endpoint of this study is to evaluate the efficacy of electrochemotherapy as a palliative treatment. Methods. This phase II study is a collaboration between two centres, one in Denmark and the other in the UK. Patients with cutaneous metastases of any histology were included. Bleomycin was administered intratumourally or intravenously followed by application of electric pulses to the tumour site. Results. Fifty-two patients were included. Complete and partial response rate was 68% and 18%, respectively, for cutaneous metastases <3 cm and 8% and 23%, respectively, for cutaneous metastases >3 cm. Treatment was well-tolerated by patients, including the elderly, and no serious adverse events were observed. Conclusions. ECT is an efficient and safe treatment and clinicians should not hesitate to use it even in the elderly

Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape

Citation: Leys, B. A., Commerford, J. L., & McLauchlan, K. K. (2017). Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape. Plos One, 12(4), 15. doi:10.1371/journal.pone.0176445Fire is a key Earth system process, with 80% of annual fire activity taking place in grassland areas. However, past fire regimes in grassland systems have been difficult to quantify due to challenges in interpreting the charcoal signal in depositional environments. To improve reconstructions of grassland fire regimes, it is essential to assess two key traits: (1) charcoal count, and (2) charcoal shape. In this study, we quantified the number of charcoal pieces in 51 sediment samples of ponds in the Great Plains and tested its relevance as a proxy for the fire regime by examining 13 potential factors influencing charcoal count, including various fire regime components (e.g. the fire frequency, the area burned, and the fire season), vegetation cover and pollen assemblages, and climate variables. We also quantified the width to length (W: L) ratio of charcoal particles, to assess its utility as a proxy of fuel types in grassland environments by direct comparison with vegetation cover and pollen assemblages. Our first conclusion is that charcoal particles produced by grassland fires are smaller than those produced by forest fires. Thus, a mesh size of 120 mu m as used in forested environments is too large for grassland ecosystems. We recommend counting all charcoal particles over 60 mu m in grasslands and mixed grass-forest environments to increase the number of samples with useful data. Second, a W: L ratio of 0.5 or smaller appears to be an indicator for fuel types, when vegetation surrounding the site is before composed of at least 40% grassland vegetation. Third, the area burned within 1060m of the depositional environments explained both the count and the area of charcoal particles. Therefore, changes in charcoal count or charcoal area through time indicate a change in area burned. The fire regimes of grassland systems, including both human and climatic influences on fire behavior, can be characterized by long-term charcoal records

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy