Polarization-resolved extinction and scattering cross-section of individual gold nanoparticles measured by wide-field microscopy on a large ensemble

We report a simple, rapid, and quantitative wide-field technique to measure the optical extinction $\sigma_{\rm ext}$ and scattering $\sigma_{\rm sca}$ cross-section of single nanoparticles using wide-field microscopy enabling simultaneous acquisition of hundreds of nanoparticles for statistical analysis. As a proof of principle, we measured nominally spherical gold nanoparticles of 40\,nm and 100\,nm diameter and found mean values and standard deviations of $\sigma_{\rm ext}$ and $\sigma_{\rm sca}$ consistent with previous literature. Switching from unpolarized to linearly polarized excitation, we measured $\sigma_{\rm ext}$ as a function of the polarization direction, and used it to characterize the asphericity of the nanoparticles. The method can be implemented cost-effectively on any conventional wide-field microscope and is applicable to any nanoparticles

Optical extinction and coherent multiphoton micro-spectroscopy of single nanoparticles

Nanoparticles of many varieties are increasingly studied for use in the physical, chemical, and biological sciences. Metallic nanoparticles exhibit morphology-dependent localised surface plasmon resonances (LSPR), which couple to propagating light, and manifest as a resonant particle polarisability at the LSPR frequency. These resonances can be harnessed for a variety of applications. Many of these applications require characterisation of NP properties, such as their optical response, summarised by the ab- sorption and scattering cross sections. Quantitative measurement of individual NPs is technically difficult, and ensemble measurement techniques, such as absorption spectroscopy, are frequently employed. However, individual NP properties can vary significantly, within the ensemble. In this work, we present a novel, and easy to implement, wide-field extinction microscopy technique, capable of analysing hundreds of nanoparticles simultaneously. Using this technique, we are able to characterise individual gold nanoparticles down to 5 nm diameter, and collate the data to produce ensemble statistics. Furthermore, we developed a program for the rapid analysis of the acquired image, enabling implementation by others in a cost-effective and efficient manner. Using the wide-field extinction technique, we have studied several sizes of gold, platinum, silver, and diamond nanoparticles. We used gold nanoparticles to pro- vide a proof of concept, and found good agreement with the literature. We also present an experimental investigation towards an in-vitro plasmon ruler. Coupled metallic NPs exhibit a LSPR, which is dependent on interparticle distance. The four-wave mixing technique we employ is phase-sensitive, allowing measurement of the shift of the res- onance frequency of gold NPs. To provide proof-of-principle of the plasmon ruler, we correlatively studied gold nanoparticle dimers, with transmission electron microscopy, and four-wave mixing microscopy. In this way, we obtained a direct measure of the interparticle distance, and could relate it to the measured phase shift in four-wave mixing

Identification of challenges to the availability and accessibility of opioids in twelve European countries:conclusions from two ATOME six-country workshops

Background: Access to many controlled medicines is inadequate in a number of European countries. This leads to deficits in the treatment of moderate to severe pain as well as in opioid agonist therapy. Objective: The study objective was to elaborate the reasons for this inadequacy. The work plan of the Access to Opioid Medication in Europe (ATOME) project included two six-country workshops. These workshops comprised a national situational analysis, drafting tailor-made recommendations for improvement and developing action plans for their implementation. Methods: In total, 84 representatives of the national Ministries of Health, national controlled substances authorities, experts representing regulatory and law enforcement authorities, leading health care professionals, and patient representatives from 13 European countries participated in either one of the workshops. The delegates used breakout sessions to identify key common challenges. Content analysis was used for the evaluation of protocols and field notes. Results: A number of challenges to opioid accessibility in the countries was identified in the domains of knowledge and educational, regulatory, legislative, as well as public awareness and training barriers that limit opioid prescription. In addition, short validity of prescriptions and bureaucratic practices resulting in overregulation impeded availablity of some essential medicines. Stigmatization and criminalisation of people who use drugs remained the major impediment to increasing opioid agonist program coverage. Conclusions: The challenges identified during outcomes of the workshops were used as the basis for subsequent dissemination and implementation activities in the ATOME project, and in some countries the workshop proceedings already served as a stepping-stone for the first changes in regulations and legislation

The optical nanosizer – quantitative size and shape analysis of individual nanoparticles by high-throughput widefield extinction microscopy

Nanoparticles are widely utilised for a range of applications, from catalysis to medicine, requiring accurate knowledge of their size and shape. Current techniques for particle characterisation are either not very accurate or time consuming and expensive. Here we demonstrate a rapid and quantitative method for particle analysis based on measuring the polarisation-resolved optical extinction cross-section of hundreds of individual nanoparticles using wide-field microscopy, and determining the particle size and shape from the optical properties. We show measurements on three samples consisting of nominally spherical gold nanoparticles of 20 nm and 30 nm diameter, and gold nanorods of 30 nm length and 10 nm diameter. Nanoparticle sizes and shapes in three dimensions are deduced from the measured optical cross-sections at different wavelengths and light polarisation, by solving the inverse problem, using an ellipsoid model of the particle polarisability in the dipole limit. The sensitivity of the method depends on the experimental noise and the choice of wavelengths. We show an uncertainty down to about 1 nm in mean diameter, and 10% in aspect ratio when using two or three color channels, for a noise of about 50 nm^2 in the measured cross-section. The results are in good agreement with transmission electron microscopy, both 2D projection and tomography, of the same sample batches. Owing to its combination of experimental simplicity, ease of access to statistics over many particles, accuracy, and geometrical particle characterisation in 3D, this 'optical nanosizer' method has the potential to become the technique of choice for quality control in next-generation particle manufacturing

Quantitative morphometric analysis of single gold nanoparticles by optical extinction microscopy: material permittivity and surface damping effects

Quantifying the optical extinction cross section of a plasmonic nanoparticle has recently emerged as a powerful means to characterize the nanoparticle morphologically, i.e., to determine its size and shape with a precision comparable to electron microscopy while using a simple optical microscope. In this context, a critical piece of information to solve the inverse problem, namely, calculating the particle geometry from the measured cross section, is the material permittivity. For bulk gold, many datasets have been reported in the literature, raising the question of which one is more adequate to describe specific systems at the nanoscale. Another question is how the nanoparticle interface, not present in the bulk material, affects its permittivity. In this work, we have investigated the role of the material permittivities on the morphometric characterization of defect-free ultra-uniform gold nanospheres with diameters of 10 nm and 30 nm, following a quantitative analysis of the polarization- and spectrally-resolved extinction cross section on hundreds of individual nanoparticles. The measured cross sections were fitted using an ellipsoid model. By minimizing the fit error or the variation of the fitted dimensions with color channel selection, the material permittivity dataset and the surface damping parameter g best describing the nanoparticles are found to be the single crystal dataset by Olmon et al. [Phys. Rev. B 86, 235147 (2012)] and g ≈ 1, respectively. The resulting nanoparticle geometries are in good agreement with transmission electron microscopy of the same sample batches, including both 2D projection and tomography

Building a taxonomy of integrated palliative care initiatives: Results from a focus group

Background Empirical evidence suggests that integrated palliative care (IPC) increases the quality of care for palliative patients and supports professional caregivers. Existing IPC initiatives in Europe vary in their design and are hardly comparable. InSuP-C, a European Union research project, aimed to build a taxonomy of IPC initiatives applicable across diseases, healthcare sectors and systems. Methods The taxonomy of IPC initiatives was developed in cooperation with an international and multidisciplinary focus group of 18 experts. Subsequently, a consensus meeting of 10 experts revised a preliminary taxonomy and adopted the final classification system. Results Consisting of eight categories, with two to four items each, the taxonomy covers the process and structure of IPC initiatives. If two items in at least one category apply to an initiative, a minimum level of integration is assumed to have been reached. Categories range from the type of initiative (items: Pathway, model or guideline) to patients' key contact (items: Nonpc specialist, pc specialist, general practitioner). Experts recommended the inclusion of two new categories: Level of care (items: Primary, secondary or tertiary) indicating at which stage palliative care is integrated and primary focus of intervention describing IPC givers' different roles (items: Treating function, advising/consulting or training) in the care process. Conclusions Empirical studies are required to investigate how the taxonomy is used in practice and whether it covers the reality of patients in need of palliative care. The InSuP-C project will test this taxonomy empirically in selected initiatives using IPC

ABRF Proteome Informatics Research Group (iPRG) 2016 Study: Inferring Proteoforms from Bottom-up Proteomics Data.

This report presents the results from the 2016 Association of Biomolecular Resource Facilities Proteome Informatics Research Group (iPRG) study on proteoform inference and false discovery rate (FDR) estimation from bottom-up proteomics data. For this study, 3 replicate Q Exactive Orbitrap liquid chromatography-tandom mass spectrometry datasets were generated from each of

Review of European guidelines on palliative sedation: a foundation for the updating of the European Association for Palliative Care framework

in 2009, the European Association for Palliative Care (EAPC) developed a framework on palliative sedation, acknowledging this practice as an important and ethically acceptable intervention of last resort for terminally ill patients experiencing refractory symptoms. Before and after that, other guidelines on palliative sedation have been developed in Europe with variations in terminology and concepts. As part of the Palliative Sedation project (Horizon 2020 Funding No. 825700), a revision of the EAPC framework is planned. The aim of this article is to analyze the most frequently used palliative sedation guidelines as reported by experts from eight European countries to inform the discussion of the new framework. The three most reported documents per country were identified through an online survey among 124 clinical experts in December 2019. Those meeting guideline criteria were selected. Their content was assessed against the EAPC framework on palliative sedation. The quality of their methodology was evaluated with the Appraisal Guideline Research and Evaluation (AGREE) II instrument. Nine guidelines were included. All recognize palliative sedation as a last-resort treatment for refractory symptoms, but the criterion of refractoriness remains a matter of debate. Most guidelines recognize psychological or existential distress as (part of) an indication and some make specific recommendations for such cases. All agree that the assessment should be multiprofessional, but they diverge on the expertise required by the attending physician/team. Regarding decisions on hydration and nutrition, it is proposed that these should be independent of those for palliative sedation, but there is no clear consensus on the decision-making process. Several weaknesses were highlighted, particularly in areas of rigor of development and applicability. The identified points of debate and methodological weaknesses should be considered in any update or revision of the guidelines analyzed to improve the quality of their content and the applicability of their recommendations

The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage

The CHD4 helicase is identified as a new component of the genome surveillance machinery in a proteomic screen for factors enriched on chromatin after ionizing radiation (see also related paper by Smeenk et al. in this issue)