Effect of Gamma and X-ray Irradiation on Polymers Commonly Used in Healthcare Products.

Synthetic organic polymers commonly are used in the construction of healthcare product and medical device components. Medical devices often are sterilized to ensure that they are free from viable microorganisms. A common technique to achieve this is using ionizing radiation, usually gamma. A trend exists in industrial sterilization to supplement gamma with alternative accelerator technologies (e.g., X-ray). In the current work, studies were performed to characterize polymer modifications caused by gamma and X-ray sterilization processes and to assess the comparative equivalency. The studies were developed to evaluate two key process parameters: dose and dose rate. Three commonly used polymers were selected: high-density polyethylene, low-density polyethylene, and polypropylene. Four grades of each family were chosen. The dose assessment involved sample exposures to both gamma and X-ray irradiation at two dose levels (30 and 55 kGy). All other processing conditions, including dose rate, were controlled at standard processing levels akin to each sterilization technology. The dose rate assessment expanded on each dose level by introducing two additional dose rate parameters. Subsequent laboratory testing used techniques to characterize physico-chemical properties of the polymers to ascertain equivalency across test groups. Initial results indicated positive levels of equivalency between gamma and X-ray irradiation.

Principles of Parametric Release: Emphasis on Data Collection and Interpretation.

Parametric release, which relies on use of process data for product release, provides many benefits. However, adoption by the sterilization industry has been slow, with release typically involving biological indicator (BI) growth responses/ dosimetry readings. The current article highlights how the data provided by the process (described through examples for ethylene oxide [EO], vaporized hydrogen peroxide [VHP], and radiation) may be better used to inform parametric release implementation. The examples involving EO and VHP demonstrated the ability of the sterilization equipment to deliver validated parameters repeatedly after the load presented was validated. For instances in which load variability has not been addressed in performance qualification, BI testing or even measurement of EO concentration cannot reliably or fully inform the impact of such variance on the validated process. "Direct" monitoring of EO concentration is a current requirement in ISO 11135:2014. Nonetheless, the findings presented here show that EO and VHP concentrations can be determined by the calculated method, rendering the use of a concentration measurement probe somewhat superfluous. In alignment with European Union good manufacturing practice Annex 17, a key requirement of parametric release is to have sufficient data to demonstrate the repeatability of the validated process. Similar to gas technologies, radiation processing strives to implement parametric release but is limited by the currently available means of measuring all critical parameters, such as photon delivery.

Accumulation and Speciation of Cobalt in Paracentrotus lividus.

Since the first human release of radionuclides on Earth at the end of the Second World War, impact assessments have been implemented. Radionuclides are now ubiquitous, and the impact of local accidental release on human activities, although of low probability, is of tremendous social and economic consequences. Although radionuclide inventories (at various scales) are essential as input data for impact assessment, crucial information on physicochemical speciation is lacking. Among the metallic radionuclides of interest, cobalt-60 is one of the most important activation products generated in the nuclear industry. In this work, a marine model ecosystem has been defined because seawater and more generally marine ecosystems are final receptacles of metal pollution. A multistep approach from quantitative uptake to understanding of the accumulation mechanism has been implemented with the sea urchin Paracentrotus lividus. In a well-controlled aquarium, the day-by-day uptake of cobalt and its quantification in different compartments of the sea urchin were monitored with various conditions of exposure by combining ICP-OES analysis and γ spectrometry. Cobalt is mainly distributed following the rating intestinal tract ≫ gonads > shell spines. Cobalt speciation in seawater and inside the gonads and the intestinal tract was determined using extended X-ray absorption fine structure (EXAFS). The cobalt inside the gonads and the intestinal tract is mainly complexed by the toposome, the main protein in the sea urchin P. lividus. Complexation with purified toposome was characterized and a complexation site combining EXAFS and AIMD (ab initio molecular dynamics) was proposed implying monodentate carboxylates.

Potential Induced Radioactivity in Materials Processed with X-ray Energy Above 5 MeV.

Section 5.1.2 of ANSI/AAMI/ISO 11137-1 states that "the potential for induced radioactivity in product shall be assessed." This article describes how compliance with this requirement may be achieved using qualified test methods. Materials of consideration are conceptually discussed, and results of testing conducted on products processed with a 7.5-MeV X-ray irradiation process are provided. As X-ray becomes more widely used in healthcare sterilization, having standard assessment protocols for activation coupled with a shared database of material test results will benefit manufacturers seeking to utilize this innovative technology.

RGD-functionalized magnetosomes are efficient tumor radioenhancers for X-rays and protons.

Although chemically synthesized ferro/ferrimagnetic nanoparticles have attracted great attention in cancer theranostics, they lack radio-enhancement efficacy due to low targeting and internalization ability. Herein, we investigated the potential of RGD-tagged magnetosomes, bacterial biogenic magnetic nanoparticles naturally coated with a biological membrane and genetically engineered to express an RGD peptide, as tumor radioenhancers for conventional radiotherapy and proton therapy. Although native and RGD-magnetosomes similarly enhanced radiation-induced damage to plasmid DNA, RGD-magnetoprobes were able to boost the efficacy of radiotherapy to a much larger extent than native magnetosomes both on cancer cells and in tumors. Combined to magnetosomes@RGD, proton therapy exceeded the efficacy of X-rays at equivalent doses. Also, increased secondary emissions were measured after irradiation of magnetosomes with protons versus photons. Our results indicate the therapeutic advantage of using functionalized magnetoparticles to sensitize tumors to both X-rays and protons and strengthen the case for developing biogenic magnetoparticles for multimodal nanomedicine in cancer therapy.

X-ray: An Effective Photon.

Following years of discussion and debate regarding the economics of X-ray radiation for sterilization of healthcare products, the benefits of the technology are now being realized. X-ray, like gamma radiation, is a process whereby energic photons penetrate to sterilize medical devices. Compared to gamma, photons in the bremsstrahlung spectrum from X-ray radiation allow for improved dose uniformity ratio, higher dose rates, and shorter process time, which provide additional opportunities for sterilization process enhancement. Such improvements may be realized in a number of ways: 1) economic, where more products may be processed on a carrier; 2) improved dose range fit; and/or 3) wider material compatibility. Despite noted benefits, X-ray sterilization has not yet been widely accepted and currently accounts for less than 5% of the contract sterilization market. This article brings X-ray sterilization into focus by sharing knowledge and experience gained over the past 10 years at the STERIS Däniken site, with an aim to identify opportunities for future medical device sterilization.

Actinide(IV) Deposits on Bone: Potential Role of the Osteopontin-Thorium Complex.

In case of a nuclear event, contamination (broad or limited) of the population or of specific workers might occur. In such a senario, the fate of actinide contaminants may be of first concern, in particular with regard to human target organs like the skeleton. To improve our understanding of the toxicological processes that might take place, a mechanistic approach is necessary. For instance, ∼50% of Pu(IV) is known from biokinetic data to accumulate in bone, but the underlining mechanisms are almost unknown. In this context, and to obtain a better description of the toxicological mechanisms associated with actinides(IV), we have undertaken the investigation, on a molecular scale, of the interaction of thorium(IV) with osteopontin (OPN) a hyperphosphorylated protein involved in bone turnover. Thorium is taken here as a simple model for actinide(IV) chemistry. In addition, we have selected a phosphorylated hexapeptide (His-pSer-Asp-Glu-pSer-Asp-Glu-Val) that is representative of the peptidic sequence involved in the bone interaction. For both the protein and the biomimetic peptide, we have determined the local environment of Th(IV) within the bioactinidic complex, combining isothermal titration calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, theoretical calculations with density functional theory, and extended X-ray absorption fine structure spectroscopy at the Th LIII edge. The results demonstrate a predominance of interaction of metal with the phosphate groups and confirmed the previous physiological studies that have highlighted a high affinity of Th(IV) for the bone matrix. Data are further compared with those of the uranyl case, representing the actinyl(V) and actinyl(VI) species. Last, our approach shows the importance of developing simplified systems [Th(IV)-peptide] that can serve as models for more biologically relevant systems.

How Do Radionuclides Accumulate in Marine Organisms? A Case Study of Europium with Aplysina cavernicola.

In the ocean, complex interactions between natural and anthropogenic radionuclides, seawater, and diverse marine biota provide a unique window through which to examine ecosystem and trophic transfer mechanisms in cases of accidental dissemination. The nature of interaction between radionuclides, the marine environment, and marine species is therefore essential for better understanding transfer mechanisms from the hydrosphere to the biosphere. Although data pertaining to the rate of global transfer are often available, little is known regarding the mechanism of environmental transport and uptake of heavy radionuclides by marine species. Among marine species, sponges are immobile active filter feeders and have been identified as hyperaccumulators of several heavy metals. We have selected the Mediterranean sponge Aplysina cavernicola as a model species for this study. Actinide elements are not the only source of radioactive release in cases of civilian nuclear events; however, their physicochemical transfer mechanisms to marine species remain largely unknown. We have targeted europium(III) as a representative of the trivalent actinides such as americium or curium. To unravel biological uptake mechanisms of europium in A. cavernicola, we have combined radiometric (γ) measurements with spectroscopic (time-resolved laser-induced fluorescence spectroscopy, TRLIFS, and X-ray absorption near-edge structure, XANES) and imaging (transmission electron microscopy, TEM, and scanning transmission X-ray microscopy, STXM) techniques. We have observed that the colloids of NaEu(CO3)2·nH2O formed in seawater are taken up by A. cavernicola with no evidence that lethal dose has been reached in our working conditions. Spectroscopic results suggest that there is no change of speciation during uptake. Finally, TEM and STXM images recorded at different locations across a sponge cross section, together with differential cell separation, indicate the presence of europium particles (around 200 nm) mainly located in the skeleton and toward the outer surface of the sponge.

Distribution and baseline values of trace elements in the sediment of Var River catchment, Southeast France.

This study reports on the determination of trace element (TE)-Li, As, Co, Cs, Cu, Pb, U, and Zn-and major element (ME)-Si, Al, Fe, Mg, Ca, Mn, Na, and K-concentrations in 18 riverbed sediments and a sediment core from the Var River catchment using inductively coupled plasma mass spectrometry (ICP-MS). The results were compared with those of a reference sediment core, and the contribution of clay and organic carbon contents in the distribution of TE and ME in the sediment samples was investigated. The mean concentrations of the ME were comparable in both core and riverbed samples and were within the natural averages. In the case of TE, the concentrations were lower in riverbed sediment samples than those found in the sediment core. High mean concentration of As was observed (7.6 µg g(-1)) in both core and riverbed sediments, relatively higher than the worldwide reported values. The obtained data indicated that the natural high level of arsenic might be originated from the parent rocks, especially metamorphic rocks surrounding granites and from Permian sediments. Statistical approach, viz., Pearson correlation matrix, was applied to better understand the correlation among TE in both riverbed and sediment core samples. No significant metallic contamination was detected in the low Var valley despite of the localization of several industrial facilities. Therefore, results confirm that the concentrations of the TE obtained in the riverbed sediments could be considered as a baseline guide for future pollution monitoring program.

Assessing the chronic effect of the bioavailable fractions of radionuclides and heavy metals on stream microbial communities: A case study at the Rophin mining site.

This study aimed to assess the potential impact of long-term chronic exposure (69 years) to naturally-occurring radionuclides (RNs) and heavy metals on microbial communities in sediment from a stream flowing through a watershed impacted by an ancient mining site (Rophin, France). Four sediment samples were collected along a radioactivity gradient (for 238U368 to 1710 Bq.Kg-1) characterized for the presence of the bioavailable fractions of radionuclides (226Ra, 210Po), and trace metal elements (Th, U, As, Pb, Cu, Zn, Fe). Results revealed that the available fraction of contaminants was significant although it varied considerably from one element to another (0 % for As and Th, 5-59 % for U). Nonetheless, microbial communities appeared significantly affected by such chronic exposure to (radio)toxicities. Several microbial functions carried by bacteria and related with carbon and nitrogen cycling have been impaired. The high values of fungal diversity and richness observed with increasing downstream contamination (H' = 4.4 and Chao1 = 863) suggest that the community had likely shifted toward a more adapted/tolerant one as evidenced, for example, by the presence of the species Thelephora sp. and Tomentella sp. The bacterial composition was also affected by the contaminants with enrichment in Myxococcales, Acidovorax or Nostocales at the most contaminated points. Changes in microbial composition and functional structure were directly related to radionuclide and heavy metal contaminations, but also to organic matter which also significantly affected, directly or indirectly, bacterial and fungal compositions. Although it was not possible to distinguish the specific effects of RNs from heavy metals on microbial communities, it is essential to continue studies considering the available fraction of elements, which is the only one able to interact with microorganisms.

Environmental Chemistry of Radionuclides : Open Questions and Perspectives.

Since the discovery of nuclear fission, atomic energy has become for mankind a source of energy, but it has also become a source of consternation. This Perspective presents and discusses the methodological evolution of the work performed in the radiochemistry laboratory that is part of the Institut de Chimie de Nice (France). Most studies in radioecology and environmental radiochemistry have intended to assess the impact and inventory of very low levels of radionuclides in specific environmental compartments. But chemical mechanisms at the molecular level remain a mystery because it is technically impossible (due to large dilution factors) to assess speciation in those systems. Ultra-trace levels of contamination and heterogeneity often preclude the use of spectroscopic techniques and the determination of direct speciation data, thus forming the bottleneck of speciation studies. The work performed in the Nice radiochemistry laboratory underlines this effort to input speciation data (using spectroscopic techniques like X ray Absorption Spectroscopy) in environmental and radioecological metrics.

What is a "Good Life": Protocol for a qualitative study to explore the viewpoint of older persons.

INTRODUCTION: Over the last fifteen years, Living Labs have been on the rise in Europe to bridge the gap between service providers, and the needs of end-users, and to speed up innovation, particularly in the field of healthcare and ageing. Ageing tends to be considered by institutions as a set of risks to be managed for older persons, illustrated in particular via the concepts of "ageing well" or "successful ageing". In this context, this project aims to define the meaning and the conditions for a good life from the point of view of older persons themselves, thereby improving institutions' recognition and support of older persons' ways of living well, rather than imposing a general definition of "successful ageing" based on functional capacity. METHODS AND ANALYSIS: This qualitative study is designed as an action research underpinned by a Living-Lab approach to co-creation. The aims are to: define the conditions for a good life as accurately as possible with older persons (Step 1); share these findings with different healthcare and service providers to adjust existing services or create new ones (Step 2); and disseminate them more broadly within the regions under study and across the scientific community (Step 3). During Step 1, the features of a "good life" will be analysed in a socio-anthropological study based on semi-directed interviews and observations made in the homes of 70 elderly people living in a wide range of accommodation types and regions. In accordance with French legislation, and as confirmed by our formal Ethics Committee, this study does not require approval. The dissemination stage is integrated into the design of this action research, and notably will provide for the appropriation of research findings by the partners of this study, by setting up creativity sessions (Step 2) and by sharing the general findings through panel discussions bringing together regional and national stakeholders (Step 3).

Predicting severity and prognosis in Parkinson's disease from brain microstructure and connectivity.

OBJECTIVES: Investigating biomarkers to demonstrate progression of Parkinson's disease (PD) is of high priority. We investigated the association of brain structural properties with progression of clinical outcomes and their ability to differentiate clinical subtypes of PD. METHODS: A comprehensive set of clinical features was evaluated at baseline and 4.5-year follow-up for 144 de-novo PD patients from the Parkinson's Progression Markers Initiative. We created a global composite outcome (GCO) by combining z-scores of non-motor and motor symptoms, motor signs, overall activities of daily living and global cognition, as a single numeric indicator of prognosis. We classified patients into three subtypes based on multi-domain clinical criteria: 'mild motor-predominant', 'intermediate' and 'diffuse-malignant'. We analyzed diffusion-weighted scans at the early drug-naïve stage and extracted fractional anisotropy and mean diffusivity (MD) of basal ganglia and cortical sub-regions. Then, we employed graph theory to calculate network properties and used network-based statistic to investigate our primary hypothesis. RESULTS: Baseline MD of globus pallidus was associated with worsening of motor severity, cognition, and GCO after 4.5 years of follow-up. Connectivity disruption at baseline was correlated with decline in cognition, and increase in GCO. Baseline MD of nucleus accumbens, globus pallidus and basal-ganglia were linked to clinical subtypes at 4.5-year of follow-up. Disruption in sub-cortical networks associated with being subtyped as 'diffuse-malignant' versus 'mild motor-predominant' after 4.5 years. CONCLUSIONS: Diffusion imaging analysis at the early de-novo stage of PD was able to differentiate clinical sub-types of PD after 4.5 years and was highly associated with future clinical outcomes of PD.

210Po sequential extraction applied to wetland soils at uranium mining sites.

Former uranium mining activities have led to the presence of naturally occurring nuclides embedded in soil. Such activities have also modified the secular equilibrium between radionuclides in 238U decay series. The objective of this paper is to quantify the long-term effect of former uranium mining activities on the behavior of the final radionuclide in the 238U-series, i.e. polonium-210 (210Po), present in soils. Soil samples are extracted from two uranium sites in France, specifically a quarried site and a natural site. The polonium distribution is studied within the various soil fractions, namely: water soluble, exchangeable, bound to carbonates, bound to iron/manganese oxides, bound to organic matter, and residual. 210Po is mainly found in the residual fraction of both study sites (87-90%), followed by the carbonates fraction (5-9%). The 210Po activity in the other fractions is very small in comparison with total activity.

Anatomical and functional organization of the human substantia nigra and its connections.

We investigated the anatomical and functional organization of the human substantia nigra (SN) using diffusion and functional MRI data from the Human Connectome Project. We identified a tripartite connectivity-based parcellation of SN with a limbic, cognitive, motor arrangement. The medial SN connects with limbic striatal and cortical regions and encodes value (greater response to monetary wins than losses during fMRI), while the ventral SN connects with associative regions of cortex and striatum and encodes salience (equal response to wins and losses). The lateral SN connects with somatomotor regions of striatum and cortex and also encodes salience. Behavioral measures from delay discounting and flanker tasks supported a role for the value-coding medial SN network in decisional impulsivity, while the salience-coding ventral SN network was associated with motor impulsivity. In sum, there is anatomical and functional heterogeneity of human SN, which underpins value versus salience coding, and impulsive choice versus impulsive action.

Speciation of americium in seawater and accumulation in the marine sponge Aplysina cavernicola.

The fate of radionuclides in the environment is a cause of great concern for modern society, seen especially in 2011 after the Fukushima accident. Among the environmental compartments, seawater covers most of the earth's surface and may be directly or indirectly impacted. The interaction between radionuclides and the marine compartment is therefore essential for better understanding the transfer mechanisms from the hydrosphere to the biosphere. This information allows for the evaluation of the impact on humans via our interaction with the biotope that has been largely undocumented up to now. In this report, we attempt to make a link between the speciation of heavy elements in natural seawater and their uptake by a model marine organism. More specifically, because the interaction of actinides with marine invertebrates has been poorly studied, the accumulation in a representative member of the Mediterranean coralligenous habitat, the sponge Aplysina cavernicola, was investigated and its uptake curve exposed to a radiotracer (241)Am was estimated using a high-purity Ge gamma spectrometer. But in order to go beyond the phenomenological accumulation rate, the speciation of americium(III) in seawater must be assessed. The speciation of (241)Am (and natural europium as its chemically stable surrogate) in seawater was determined using a combination of different techniques: Time-Resolved Laser-Induced Fluorescence (TRLIF), Extended X-ray Absorption Fine Structure (EXAFS) at the LIII edge, Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy and Scanning Electron Microscopy (SEM) and the resulting data were compared with the speciation modeling. In seawater, the americium(III) complex (as well as the corresponding europium complex, although with conformational differences) was identified as a ternary sodium biscarbonato complex, whose formula can be tentatively written as NaAm(CO3)2·nH2O. It is therefore this chemical form of americium that is accumulated by the sponge A. cavernicola.

Network structure of brain atrophy in de novo Parkinson's disease.

We mapped the distribution of atrophy in Parkinson's disease (PD) using magnetic resonance imaging (MRI) and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation-based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

Which activities threaten independent living of elderly when becoming problematic: inspiration for meaningful service robot functionality.

PURPOSE: In light of the increasing elderly population and the growing demand for home care, the potential of robot support is given increasing attention. In this paper, an inventory of activities was made that threaten independent living of elderly when becoming problematic. Results will guide the further development of an existing service robot, the Care-O-bot®. METHOD: A systematic literature search of PubMed was performed, focused on the risk factors for institutionalization. Additionally, focus group sessions were conducted in the Netherlands, United Kingdom and France. In these focus group sessions, problematic activities threatening the independence of elderly people were discussed. Three separate target groups were included in the focus group sessions: (1) elderly persons (n = 41), (2) formal caregivers (n = 40) and (3) informal caregivers (n = 32). RESULTS: Activities within the International Classification of Functioning domains mobility, self-care, and interpersonal interaction and relationships were found to be the most problematic. CONCLUSIONS: A distinct set of daily activities was identified that may threaten independent living, but no single activity could be selected as the main activity causing a loss of independence as it is often a combination of problematic activities that is person-specific. Supporting the problematic activities need not involve a robotic solution.