Rapid, one-pot procedure to synthesise 103Pd:Pd@Au nanoparticles en route for radiosensitisation and radiotherapeutic applications

The radioisotope palladium (103Pd), encapsulated in millimetre-size seed implants, is widely used in prostate cancer brachytherapy. Gold nanoparticles (Au NPs) distributed in the vicinity of 103Pd radioactive implants, strongly enhance the therapeutic dose of radioactive implants (radiosensitisation effect). A new strategy under development to replace millimetre-size implants, consist in injecting radioactive NPs in the affected tissues. The development of 103Pd@Au NPs distributed in the diseased tissue, could increase the uniformity of treatment (compared with massive seeds), while enhancing the radiotherapeutic dose to the cancer cells (through Au-mediated radiosensitisation effect). To achieve this goal, it is necessary to develop a rapid, efficient, one-pot and easy-to-automatise procedure, allowing the synthesis of coreshell Pd@Au NPs. The novel synthesis route proposed here enables the production of Pd@Au NPs in not more than 4h, in aqueous media, with minimal manipulations, and relying on biocompatible and non-toxic molecules. This rapid multi-step process consists of the preparation of ultra-small Pd NPs by chemical reduction of an aqueous solution of H2PdCl4 supplemented with ascorbic acid (AA) as reducing agent and 2, 3-meso-dimercaptosuccinic acid (DMSA) as a capping agent. Pd conversion yields close to 87% were found, indicating the efficiency of the reaction process. Then Pd NPs were used as seeds for the growth of a gold shell (Pd@Au), followed by grafting with polyethylene glycol (PEG) to ensure colloidal stability. Pd@Au-PEG (TEM: 20.2 ± 12.1 nm) formed very stable colloids in saline solution as well as in cell culture medium. The physico-chemical properties of the particles were characterised by FTIR, XPS, and UV-vis. spectroscopies. The viability of PC3 human prostate cancer cells was not affected after a 24-h incubation cycle with Pd@Au-PEG NPs to concentrations up to 4.22 mM Au. Finally, suspensions of Pd@Au-PEG NPs measured in computed tomography (CT) are found to attenuate X-rays more efficiently than commercial Au NPs CT contrast media. A proof-of-concept was performed to demonstrate the possibility synthesise radioactive 103Pd:Pd@Au-PEG NPs. This study reveals the possibility to synthesise Pd@Au NPs rapidly (including radioactive 103Pd:Pd@Au-PEG NPs), and following a methodology that respects all the strict requirements underlying the production of NPs for radiotherapeutic use (rapidity, reaction yield, colloidal stability, NPs concentration, purification)

Dynamic correspondence principle in the viscoelasticity of metallic glasses

International audienc

The Impact of Upcoming Treatments in Huntington's Disease: Resource Capacity Limitations and Access to Care Implications.

BACKGROUND The most advanced disease-modifying therapies (DMTs) in development for Huntington's disease (HD) require intrathecal (IT) administration, which may create or exacerbate bottlenecks in resource capacity. OBJECTIVE To understand the readiness of healthcare systems for intrathecally administered HD DMTs in terms of resource capacity dynamics and implications for patients' access to treatment. METHODS Forty HD centres across 12 countries were included. Qualitative and quantitative data on current capacity in HD centres and anticipated capacity needs following availability of a DMT were gathered via interviews with healthcare professionals (HCPs). Data modelling was used to estimate the current capacity gap in HD centres. RESULTS From interviews with 218 HCPs, 25% of HD centres are estimated to have the three components required for IT administration (proceduralists, nurses and facilities). On average, 114 patients per centre per year are anticipated to receive intrathecally administered DMTs in the future. At current capacity, six of the sampled centres are estimated to be able to deliver DMTs to all the anticipated patients based on current resources. The estimated waiting time for IT administration at current capacity will average 60 months (5 years) by the second year after DMT availability. CONCLUSION Additional resources are needed in HD centres for future DMTs to be accessible to all anticipated patients. Timely collaboration by the HD community will be needed to address capacity gaps. Healthcare policymakers and payers will need to address costs and navigate challenges arising from country- or region-specific healthcare delivery schemes

Handling Planned and Unplanned Missing Data in a Longitudinal Study

While analyzing data, researchers are often faced with missing values. This is especially common in longitudinal studies in which participants might skip assessments. Unwanted missing data can introduce bias in the results and should thus be handled appropriately. However, researchers can sometimes want to include missing values in their data collection design to reduce its length and cost, a method called ``planned missingness.'' This paper review the recommended practices for handling both planned and unplanned missing data, with a focus on longitudinal studies. The current guidelines suggest to either use Full Information Maximum Likelihood or Multiple Imputation. Those techniques are illustrated with R code in the context of a longitudinal study with a representative Canadian sample on the psychological impacts of the COVID-19 pandemic

A reference case for economic evaluations in osteoarthritis: An expert consensus article from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

Background: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach. Objectives: To develop a reference case specific for economic studies in OA, including the standard optimal care, with which to judge new pharmacologic and non-pharmacologic interventions. Methods: Four subgroups of an ESCEO expert working group on economic assessments (13 experts representing diverse aspects of clinical research and/or economic evaluations) were charged with producing lists of recommendations that would potentially improve the comparability of economic analyses in OA: outcome measures, comparators, costs and methodology. These proposals were discussed and refined during a face-to-face meeting in 2013. They are presented here in the format of the recommendations of the recently published Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement, so that an initiative on economic analysis methodology might be consolidated with an initiative on reporting standards. Results: Overall, three distinct reference cases are proposed, one for each hand, knee and hip OA; with diagnostic variations in the first two, giving rise to different treatment options: interphalangeal or thumb-based disease for hand OA and the presence or absence of joint malalignment for knee OA. A set of management strategies is proposed, which should be further evaluated to help establish a consensus on the "standard optimal care" in each proposed reference case. The recommendations on outcome measures, cost itemisation and methodological approaches are also provided. Conclusions: The ESCEO group proposes a set of disease-specific recommendations on the conduct and reporting of economic evaluations in OA that could help the standardisation and comparability of studies that evaluate therapeutic strategies of OA in terms of costs and effectiveness

Does hyperthermia constrain flight duration in a short-distance migrant?

While some migratory birds perform non-stop flights of over 11 000 km, many species only spend around 15% of the day in flight during migration, posing a question as to why flight times for many species are so short. Here, we test the idea that hyperthermia might constrain flight duration (FD) in a short-distance migrant using remote biologging technology to measure heart rate, hydrostatic pressure and body temperature in 19 migrating eider ducks (Somateria mollissima), a short-distance migrant. Our results reveal a stop-and-go migration strategy where migratory flights were frequent (14 flights day(−1)) and short (15.7 min), together with the fact that body temperature increases by 1°C, on average, during such flights, which equates to a rate of heat storage index (HSI) of 4°C h(−1). Furthermore, we could not find any evidence that short flights were limited by heart rate, together with the fact that the numerous stops could not be explained by the need to feed, as the frequency of dives and the time spent feeding were comparatively small during the migratory period. We thus conclude that hyperthermia appears to be the predominant determinant of the observed migration strategy, and suggest that such a physiological limitation to FD may also occur in other species. This article is part of the themed issue ‘Moving in a moving medium: new perspectives on flight’