Optical properties of planar chiral meta-materials

The polarization state of visible light is found to be altered upon reflection from artificial two-dimensional chiral media. Arrays of metallic planar chiral structures were fabricated by electron beam lithography and ion beam milling. The characteristic dimensions on the chiral elements correspond to wavelengths in the near-IR. Our chiral media are found to induce strong polarization effects, with the handedness of individual elements having a direct effect on the sense and magnitude of rotation of the diffracted light

Elucidating cylindrospermopsin toxicity via synthetic analogues: An in vitro approach

© 2019 Elsevier Ltd Cylindrospermopsin (CYN) is an alkaloid biosynthesized by selected cyanobacteria, the cyto- and genotoxic properties of which have been studied extensively by in vitro and in vivo experimental models. Various studies have separately established the role of uracil, guanidine and hydroxyl groups in CYN-induced toxicity. In the present study, we have prepared five synthetic analogues that all possess a uracil group but had variations in the other functionality found in CYN. We compared the in vitro toxicity of these analogues in common carp hepatocytes by assessing oxidative stress markers, DNA fragmentation and apoptosis. All the analogues tested induced generation of reactive oxygen species, lipid peroxidation (LPO) and DNA fragmentation. However, the greatest increase in LPO and increase in caspase-3 activity, an apoptosis marker, was demonstrated by an analogue containing guanidine, hydroxyl and uracil functionalities similar to those found in CYN but lacking the complex tricyclic structure of CYN. We also report a crystal structure of an analogue lacking the hydroxyl group found in CYN which does not show intramolecular H-bonding interactions between the guanidine and the uracil functionalities. The observations made in this work supports the hypothesis that CYN toxicity is a result of an interplay between both of the uracil, hydroxyl and guanidine functional groups.This research was partially funded by the Ministry of Education and Science of Ukraine (program for support young fellows MV-1) and by the BEACON (ERDF) program and the EPSRC. Thanks are given to the EPSRC for a fellowship (DE, EP/J01821X/1), the BEACON (ERDF) program for support (PJM, DE) and to the National Mass Spectrometry Facility at Swansea.Published versio

Chiral gratings-a new class of polarization sensitive metamaterials

Summary form only given. Metallic bilayered structures with chirality and inductive coupling are predicted to show huge optical polarization rotatory power resembling that of liquid crystals. The semi-chiral planar gratings described here belong to a distinctively different class of 2D structures known as planar chiral structures

Insufficient Impact: Limited Implementation of Federal Regulatory Changes to Methadone and Buprenorphine Access in Arizona During COVID-19

Introduction: This study examined the impact of federal regulatory changes on methadone and buprenorphine treatment during COVID-19 in Arizona. Methods: A cohort study of methadone and buprenorphine providers from September 14, 2021 to April 15, 2022 measured the proportion of 6 treatment accommodations implemented at 3 time periods: before COVID-19, during Arizona's COVID-19 shutdown, and at the time of the survey completion. Accommodations included (1) telehealth, (2) telehealth buprenorphine induction, (3) increased multiday dosing, (4) license reciprocity, (5) home medications delivery, and (6) off-site dispensing. A multilevel model assessed the association of treatment setting, rurality, and treatment with accommodation implementation time. Results: Over half (62.2%) of the 74-provider sample practiced in healthcare settings not primarily focused on addiction treatment, 19% practiced in methadone clinics, and 19% practiced in treatment clinics not offering methadone. Almost half (43%) were unaware of the regulatory changes allowing treatment accommodation. Telehealth was most frequently reported, increasing from 30% before COVID-19 to 80% at the time of the survey. Multiday dosing was the only accommodation substantially retracted after COVID-19 shutdown: from 41% to 23% at the time of the survey. Providers with higher patient limits were 2.5–3.2 times as likely to implement telehealth services, 4.4 times as likely to implement buprenorphine induction through telehealth, and 15.2–20.9 times as likely to implement license reciprocity as providers with lower patient limits. Providers of methadone implemented 12% more accommodations and maintained a higher average proportion of implemented accommodations during the COVID-19 shutdown period but were more likely to reduce the proportion of implemented accommodations (a 17-percentage point gap by the time of the survey). Conclusions: Federal regulatory changes are not sufficient to produce a substantive or sustained impact on provider accommodations, especially in methadone medical treatment settings. Practice change interventions specific to treatment settings should be implemented and studied for their impact

Preliminary evidence of reductive stress in human cytotoxic T-cells following exercise

This study investigated immunophenotypic differences in intracellular thiol redox state of peripheral blood mononuclear cells (PBMCs) isolated from trained (TR, n=9, mean {plus minus} SD: age 28 {plus minus} 5 years; BMI 23.2 {plus minus} 2.6 kg·m2; VO2max 56.9 {plus minus} 6.1 ml·kg-1·min-1) and recreationally active (RA, n=11, mean {plus minus} SD: age 27 {plus minus} 6 years; BMI 24.2 {plus minus} 3.7 kg·m2; VO2max 45.1 {plus minus} 6.4 ml·kg-1·min-1) participants before and after a maximal aerobic exercise tolerance test. Blood samples were taken before (PRE), during (sample acquired at 70% HRmax), immediately (POST+0) and 15 minutes post-exercise (POST+15). PBMCs were isolated and reduced thiol analysis (fluorescein-5 maleimide (F5M)) by immunophenotype (CD3+, CD4+ and CD8+) was performed using flow cytometry. A significant increase in cellular F5M fluorescence was observed in CD3+ T-cells at POST+0, with changes driven to a greater extent by CD8+ T-cells (fold change in both groups CD4: +2.3, CD8: +2.8; p<0.05). Further analysis revealed a population of highly reduced CD8+ T-cells (CD8+T-reduced+) that significantly increased from PRE to POST+0 in RA participants only (RA: +272 cell/µL, p<0.05). To further understand these results, CD8+T-reduced+ and CD8+T-reduced- cells were analysed for immunophenotype in response to the same exercise protocol (n=6, mean {plus minus} SD: age 24 {plus minus} 5 years; BMI 25.7 {plus minus} 4.1 kg·m-2; VO2max 41.33 {plus minus} 7.63 ml·kg-1·min-1). CD8+T-reduced+ had significantly less lymphoid homing potential (CCR7) POST+0 compared to PRE. This study is the first to demonstrate that lymphocyte populations become more reductive in response to acute exercise

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

Climate change promotes parasitism in a coral symbiosis.

Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change

In Situ Monitoring of Intracellular Glucose and Glutamine in CHO Cell Culture

The development of processes to produce biopharmaceuticals industrially is still largely empirical and relies on optimizing both medium formulation and cell line in a product-specific manner. Current small-scale (well plate-based) process development methods cannot provide sufficient sample volume for analysis, to obtain information on nutrient utilization which can be problematic when processes are scaled to industrial fermenters. We envision a platform where essential metabolites can be monitored non-invasively and in real time in an ultra-low volume assay in order to provide additional information on cellular metabolism in high throughput screens. Towards this end, we have developed a model system of Chinese Hamster Ovary cells stably expressing protein-based biosensors for glucose and glutamine. Herein, we demonstrate that these can accurately reflect changing intracellular metabolite concentrations in vivo during batch and fed-batch culture of CHO cells. The ability to monitor intracellular depletion of essential nutrients in high throughput will allow rapid development of improved bioprocesses

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Recognition of depression, anxiety, and alcohol abuse in a Chinese rural sample: a cross-sectional study

Background Under-utilization of mental health services is a global health issue. Recognition of mental disorders, as the first step to seeking help from professional sources, has been well studied in developed countries, yet little is known about the situation in rural areas of developing countries like China. The purpose of the study is to understand the recognition of depression, anxiety, and alcohol abuse and its predictive factors in a Chinese rural sample Methods Face-to-face interviews were conducted on a representative rural adult sample in a cross-sectional study in China (N = 2052). Respondents were presented with three vignettes depicting depression, anxiety and alcohol abuse and asked to label the disorder and its cause to assess their recognition of the three mental disorders. They also completed the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Scale (GAD-7), and the Alcohol Use Disorders Identification Test (AUDIT) to assess their current mental health status. Results The alcohol abuse vignette was more frequently attributed as a mental problem than the depression vignette and anxiety vignette. The correct labeling rate was 16.1 % in the depression vignette, 15.5 % in the anxiety vignette, and 58.2 % in the alcohol vignette. Higher education is the common and also strongest factor positively predicting the recognition of all three vignettes. Beyond that, being female is an independent predictor of correct recognition of alcohol abuse, while recognition of depression and anxiety were positively predicted by younger age. Conclusions Lower recognition of depression and anxiety as compared to alcohol abuse confirms the importance and need to increase the public’s awareness and knowledge about common mental disorders. Recognition of common mental disorders could be improved through general public campaign and education, while paying attention to the unique predictive factors for each specific disorder and implement targeted intervention