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Surface-enhanced Raman scattering (SERS) remains a significant area of research since it's discovery 50 years ago. The surface-based technique has been used in a wide variety of fields, most prominently in chemical detection, cellular imaging and medical diagnostics, offering high sensitivity and specificity when probing and quantifying a chosen analyte or monitoring nanoparticle uptake and accumulation. However, despite its promise, SERS is mostly confined to academic laboratories and is not recognised as a gold standard analytical technique. This is due to the variations that are observed in SERS measurements, mainly caused by poorly characterised SERS substrates, lack of universal calibration methods and uncorrelated results. To convince the wider scientific community that SERS should be a routinely used analytical technique, the field is now focusing on methods that will increase the reproducibility of the SERS signals and how to validate the results with more well-established techniques. This review explores the difficulties experienced by SERS users, the methods adopted to reduce variation and suggestions of best practices and strategies that should be adopted if one is to achieve absolute quantification. [ABSTRACT FROM AUTHOR]

Primary ciliary dyskinesia (PCD) is a rare genetic condition characterized by destructive respiratory disease and laterality abnormalities due to randomized left–right body asymmetry. In men, PCD is also often associated with infertility due to immotile sperm owing to a malfunction of the sperm flagella. Pathogenic mutations have been found in more than 50 genes. Nonetheless, not all patients with PCD experience infertility. Therefore, to better understand the impact of PCD-associated mutations on male fertility, it is necessary to clarify the role of these genes in spermatogenesis. The CCDC103 p.His154Pro mutation has a high prevalence in PCD. Here, we present the identification and functional analysis of a biallelic mutation in CCDC103 identified in a familial case of PCD associated with male infertility. The biallelic CCDC103 mutations, NM_213607:c.161_162del(p.His55Serfs ∗9) and NM_213607:c.461A>C (p.His154Pro), were identified by whole-exome sequencing. Sanger sequencing validation was performed on all available family members, and the mutation was recessively separated with an infertility phenotype. The c.161_162del mutation breaks the reading frame of the protein and, therefore, is predicted to produce a nonfunctional protein. The tertiary structure of CCDC103-mutated protein indicated a significant conformational change that likely affected protein function. Transmission electron microscopy of spermatozoa showed that both the mid and principal regions of the flagellum lacked dynein arms, which was confirmed via immunofluorescence staining. Using the method of laser-assisted immotile sperm selection combined with intracytoplasmic sperm injection, the patient’s wife has a successful clinical pregnancy. These results extend the phenotype spectrum of the CCDC103 mutation in PCD. [ABSTRACT FROM AUTHOR]

Is Raman spectroscopy applicable for analytical purposes? Although Raman spectroscopy is a commonly used technique for analyzing sample characteristics and has numerous benefits, it still has several significant limitations that hinder the current tendency to produce the same results regardless of location, equipment, or operator. Overcoming these drawbacks may help to further the development of personalized medicine, diagnosis and treatment, the development of work protocols, and the pursuit of consistent and repeatable performance across all fields. Interlaboratory studies are currently the best way to do this. In this study, we reviewed the interlaboratory studies on Raman spectroscopy conducted to highlight the importance of moving to quantitative analysis in controlled environments. The advantages of Raman spectroscopy, including its high molecular specificity, short spectrum acquisition time, and excellent component identification capabilities, were clearly stated in all experiments. The Raman spectroscopy lab is taking small steps toward analytical applications by figuring out how to accurately predict concentrations in the relevant range of concentrations, developing and verifying the technology, and producing homogenous samples for those investigations. [ABSTRACT FROM AUTHOR]

CD123, the alpha chain of the IL-3 receptor, is an attractive target for acute myeloid leukemia (AML) treatment. However, cytotoxic antibodies or T cell engagers targeting CD123 had insufficient efficacy or safety in clinical trials. We show that expression of CD64, the high-affinity receptor for human IgG, on AML blasts confers resistance to anti-CD123 antibody-dependent cell cytotoxicity (ADCC) in vitro. We engineer a trifunctional natural killer cell engager (NKCE) that targets CD123 on AML blasts and NKp46 and CD16a on NK cells (CD123-NKCE). CD123-NKCE has potent antitumor activity against primary AML blasts regardless of CD64 expression and induces NK cell activation and cytokine secretion only in the presence of AML cells. Its antitumor activity in a mouse CD123+ tumor model exceeds that of the benchmark ADCC-enhanced antibody. In nonhuman primates, it had prolonged pharmacodynamic effects, depleting CD123+ cells for more than 10 days with no signs of toxicity and very low inflammatory cytokine induction over a large dose range. These results support clinical development of CD123-NKCE. Leukemia cells resistant to CD123-targeted therapies are susceptible to a trifunctional NK cell engager. [ABSTRACT FROM AUTHOR]

Purpose: Transcriptomic-based approaches are being developed to meet the needs for large-scale radiation dose and injury assessment and provide population triage following a radiological or nuclear event. This review provides background and definition of the need for new biodosimetry approaches, and summarizes the major advances in this field. It discusses some of the major model systems used in gene signature development, and highlights some of the remaining challenges, including individual variation in gene expression, potential confounding factors, and accounting for the complexity of realistic exposure scenarios. Conclusions: Transcriptomic approaches show great promise for both dose reconstruction and for prediction of individual radiological injury. However, further work will be needed to ensure that gene expression signatures will be robust and appropriate for their intended use in radiological or nuclear emergencies. [ABSTRACT FROM AUTHOR]

Radiotherapy is now recognized as a pillar in the fight against cancer. Two different types are currently used in clinical practice: (1) external beam radiotherapy, using high-energy X-rays or electron beams, both in the MeV-range, and (2) intraoperative radiotherapy, using low-energy X-rays (up to 50 keV) and MeV-range electron beams. Versatile detectors able to measure the radiation dose independently from the radiation nature and energy are therefore extremely appealing to medical physicists. In this work, a dosimeter based on a high-quality single-crystal synthetic diamond sample was designed, fabricated and characterized under low-energy X-rays, as well as under high-energy pulsed X-rays and electron beams, demonstrating excellent linearity with radiation dose and dose-rate. Detector sensitivity was measured to be 0.299 ± 0.002 µC/Gy under 6 MeV X-ray photons, and 0.298 ± 0.004 µC/Gy under 6 MeV electrons, highlighting that the response of the diamond dosimeter is independent of the radiation nature. Moreover, in the case of low-energy X-rays, an extremely low limit of detection (23 nGy/s) was evaluated, pointing out the suitability of the device to radiation protection dosimetry. [ABSTRACT FROM AUTHOR]

Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect of each exposure and interaction mode between these tissues would enable label free assessment of the effect of radiotherapeutic treatment in practice. In this study Fourier transform Infrared microspectroscopic imaging was employed to analyse an in-vitro model of radiotherapeutic treatment for prostate cancer, in which a normal cell line (PNT1A) was exposed to low-dose X-ray radiation from the scattered treatment beam, and also to irradiated cell culture medium (ICCM) from a cancer cell line exposed to a treatment relevant dose (2 Gy). Various exposure modes were studied and reference was made to previously acquired data on cellular survival and DNA double strand break damage. Spectral analysis with manifold methods, linear spectral fitting, non-linear classification and non-linear regression approaches were found to accurately segregate spectra on irradiation type and provide a comprehensive set of spectral markers which differentiate on irradiation mode and cell fate. The study demonstrates that high dose irradiation, low-dose scatter irradiation and radiation-induced bystander exposure (RIBE) signalling each produce differential effects on the cell which are observable through spectroscopic analysis. [ABSTRACT FROM AUTHOR]

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms. [ABSTRACT FROM AUTHOR]

Recent use of very small photon beams (down to 4 mm) in stereotactic radiotherapy requires new detectors to accurately determine the delivered dose. Diamond detectors have been presented in the literature as an attractive candidate for this application, due to their small detection volume and the diamond atomic number (Z=6) which is close to water effective atomic number (Zeff∼7.42). However, diamond exhibits a density 3.51 times greater than that of water and recent studies using Monte Carlo simulations have demonstrated the drawback of a high-density detector on small beam output factors. The current study focuses on geometrical parameters of diamond detector, namely, the diamond dimensions and the electrode geometry, in order to solve the dosimetric issues still observed in small photon beams with diamond detectors. To give better insights to these open questions, we have used both computational method and experimental analysis. This study highlighted that reducing diamond dimensions is crucial for small beam output factor measurements and to limit the influence of its high density. Furthermore, electrodes covering the whole diamond surface were essential for a dose rate independence of the diamond detector. The optimal dosimeter derived from this work presented small diamond dimensions of approximately 1-1-0.15mm3, with diamond-like-carbon electrodes covering the whole diamond surface. A dose rate independence of this diamond detector (better than 0.5% over a wide range of dose rates available on a stereotactic dedicated facility) was obtained due to the electrode geometry. Concerning the output factor measurements, a good agreement (better than 1.1%) was observed between this carbon material detector and two types of passive dosimeters (LiF microcubes and EBT2 radiochromic films) for all beam sizes except the smallest field of 0.6-0.6 cm2 with a deviation of 2.6%. This new study showed the high performance of this diamond detector in small photon beams, in comparison with various commercially available passive and active dosimeters. [ABSTRACT FROM AUTHOR]

We present optically tunable operations of deoxyribonucleic acid (DNA) biopolymer devices, where a single high-resistance state, write-once read-many-times memory state, write-read-erase memory state, and single low-resistance state can be achieved by controlling UV irradiation time. The device is a simple sandwich structure with a spin-coated DNA biopolymer layer sandwiched by two electrodes. Upon irradiation, the electrical properties of the device are adjusted owing to a phototriggered synthesis of silver nanoparticles in DNA biopolymer, giving rise to multiple switching scenarios. This technique, distinct from the strategy of doping of pre-formed nanoparticles, enables a post-film fabrication process for achieving optically controlled memory device operations, which provides a more versatile platform to fabricate organic memory and optoelectronic devices. [ABSTRACT FROM AUTHOR]

Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life exposure scenarios. For the dicentric chromosome assay (DCA), blood tubes were located at anthropomorphic phantoms positioned in different geometries and were irradiated with a 1.36 TBq 192Ir-source. For each exposure condition, dose estimates were provided by at least one laboratory and for four conditions by 17 participating RENEB laboratories. Three radio-photoluminescence glass dosimeters were placed at each tube to assess reference doses. The DCA results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for reference doses as well as for DCA doses estimates. The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation. [ABSTRACT FROM AUTHOR]

In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance. Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min−1, and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose. This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z- and U-tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model. Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way. [ABSTRACT FROM AUTHOR]

For triage purposes following a nuclear accident or a terrorist event, gene expression biomarkers in blood have been demonstrated to be good bioindicators of ionizing radiation (IR) exposure and can be used to assess the dose received by exposed individuals. Many IR-sensitive genes are regulated by the DNA damage response pathway, and modulators of this pathway could potentially affect their expression level and therefore alter accurate dose estimations. In the present study, we addressed the potential influence of temperature, sample transport conditions and the blood cell fraction analyzed on the transcriptional response of the following radiation-responsive genes: FDXR, CCNG1, MDM2, PHPT1, APOBEC3H, DDB2, SESN1, P21, PUMA, and GADD45. Whole blood from healthy donors was exposed to a 2 Gy X-ray dose with a dose rate of 0.5 Gy/min (output 13 mA, 250 kV peak, 0.2 mA) and incubated for 24 h at either 37, 22, or 4 °C. For mimicking the effect of transport conditions at different temperatures, samples incubated at 37 °C for 24 h were kept at 37, 22 or 4 °C for another 24 h. Comparisons of biomarker responses to IR between white blood cells (WBCs), peripheral blood mononuclear cells (PBMCs) and whole blood were carried out after a 2 Gy X-ray exposure and incubation at 37 °C for 24 hours. Hypothermic conditions (22 or 4 °C) following irradiation drastically inhibited transcriptional responses to IR exposure. However, sample shipment at different temperatures did not affect gene expression level except for SESN1. The transcriptional response to IR of specific genes depended on the cell fraction used, apart from FDXR, CCNG1, and SESN1. In conclusion, temperature during the incubation period and cell fraction but not the storing conditions during transport can influence the transcriptional response of specific genes. However, FDXR and CCNG1 showed a consistent response under all the different conditions tested demonstrating their reliability as individual biological dosimetry biomarkers. [ABSTRACT FROM AUTHOR]

This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal exposures are characterized by a spatially inhomogeneous irradiation of the body, which is potentially prolonged over large periods and variable over time, is particularly problematic for biological and electron paramagnetic resonance (EPR) dosimetry methods when compared with external exposures. The paper gives initially specific information about internal dosimetry methods, the most common cytogenetic techniques used in biological dosimetry and EPR dosimetry applied to tooth enamel. Based on real-case scenarios, dose estimates obtained from bioassay data as well as with biological and/or EPR dosimetry are compared and critically discussed. In most of the scenarios presented, concomitant external exposures were responsible for the greater portion of the received dose. As no assay is available which can discriminate between radiation of different types and different LETs on the basis of the type of damage induced, it is not possible to infer from these studies specific conclusions valid for incorporated radionuclides alone. The biological dosimetry assays and EPR techniques proved to be most applicable in cases when the radionuclides are almost homogeneously distributed in the body. No compelling evidence was obtained in other cases of extremely inhomogeneous distribution. Retrospective dosimetry needs to be optimized and further developed in order to be able to deal with real exposure cases, where a mixture of both external and internal exposures will be encountered most of the times. [ABSTRACT FROM AUTHOR]

FVC z score: normal EM vs IDA/CA/MTD: P =.012; ODA vs IDA/CA/MTD: P =.009; ODA/IDA vs IDA/CA/MTD: P =.046. FEV SB 1 sb /FVC z score: normal EM vs IDA/CA/MTD: P =.001; ODA/IDA vs IDA/CA/MTD: P =.020; ODA vs IDA/CA/MTD: P =.047. IDA/CA/MTD vs ODA/IDA: P =.036; CCDC39 and CCDC40 vs DNAH5: P <.0001; CCDC39 and CCDC40 vs DNAH11: P <.0001; PsA infection vs other infection: P =.0002; PsA infection vs uninfected: P <.0001; other infections vs uninfected: P = not significant. [Extracted from the article]

Ciliopathy insights: Primary ciliary dyskinesia (PCD) results from genetic mutations and structural defects that impair the motility of cilia, the cellular protrusions that sweep mucus along the surface of the airway. Here, Liu and colleagues developed a quantitative imaging workflow to improve the diagnosis of PCD. Using super-resolution microscopy on nasal airway cells isolated from patients with PCD, the authors detected mislocalized PCD-related proteins, cellular structural defects, and impairments in ciliary beating. These imaging and analysis methods could help complement standard methods of diagnosis, such as genetic testing, and could provide insight into pathology caused by variants of uncertain significance. Airway clearance of pathogens and particulates relies on motile cilia. Impaired cilia motility can lead to reduction in lung function, lung transplant, or death in some cases. More than 50 proteins regulating cilia motility are linked to primary ciliary dyskinesia (PCD), a heterogeneous, mainly recessive genetic lung disease. Accurate PCD molecular diagnosis is essential for identifying therapeutic targets and for initiating therapies that can stabilize lung function, thereby reducing socioeconomic impact of the disease. To date, PCD diagnosis has mainly relied on nonquantitative methods that have limited sensitivity or require a priori knowledge of the genes involved. Here, we developed a quantitative super-resolution microscopy workflow: (i) to increase sensitivity and throughput, (ii) to detect structural defects in PCD patients' cells, and (iii) to quantify motility defects caused by yet to be found PCD genes. Toward these goals, we built a localization map of PCD proteins by three-dimensional structured illumination microscopy and implemented quantitative image analysis and machine learning to detect protein mislocalization, we analyzed axonemal structure by stochastic optical reconstruction microscopy, and we developed a high-throughput method for detecting motile cilia uncoordination by rotational polarity. Together, our data show that super-resolution methods are powerful tools for improving diagnosis of motile ciliopathies. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to construct a calibration curve for high-dose exposure using cell fusion-induced premature chromosome condensation (PCC). Some of the associated practicalities and methodological details were also investigated. Materials and methods: Peripheral blood from two donors was used. PCC mediated by fusing mitotic CHO cells with interphase lymphocytes was carried out. Lymphocytes were irradiated with 60Co (0–20 Gy) and held at 37 °C for 24 h post exposure. Results: The protocol for PCC induction was effective at all doses and the number of rings increased with increasing dose. No significant difference was found between the donors (p =.896) and data were pooled. Ring aberration frequencies followed a Poisson distribution and the dose-response relationship favored a linear fitting: Y = 0.0007(±0.0004)+0.0186(±0.001)×D. Blind tests showed that the estimated doses were all within the 95% confidence limits of the delivered doses. This study has shown that it is valid to score only 100 cells per sample in a triage mode for doses above 5 Gy and that it is valid to score only hollow rings to reduce the scoring time. Conclusion: Scoring rings in cell fusion-induced PCC assay can be a feasible and fast approach for the analysis of high-dose exposures. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of primary ciliary dyskinesia (PCD) relies on a combination of tests. High-speed video microscopy analysis (HSVA) is widely used to contribute to the diagnosis. It can be analyzed on the day of diagnostic consultation, but the qualitative analyses are subjective. Diagnostic accuracy and reliability of assessing ciliary function have not been robustly evaluated. We aimed to establish the accuracy of HSVA to diagnose PCD compared with a combination of tests, and to assess the interobserver reliability of HSVA analysis.Methods: We randomly selected and anonymized archived videos from 120 patients seen at three UK PCD centers. Three experienced scientists independently reviewed six videos per patient, using a standardized proforma, blinded to diagnostic and clinical data. We compared study outcomes with two references: (1) a combination of diagnostic tests in accordance with the European Respiratory Society PCD diagnostic guidelines and (2) original clinical outcome determined by all available diagnostic tests.Results: HSVA had excellent sensitivity and specificity to diagnose PCD: (1) 100% and 96%, respectively, compared with ERS guidelines, and (2) 96% and 91% compared with diagnostic outcomes. There was high interobserver agreement for "PCD-positive" outcomes (κ = 0.7).Conclusions: Specialist scientists accurately diagnosed PCD using HSVA, with high interobserver agreement. HSVA can be reliably used to counsel patients and commence treatment on the day of testing while awaiting confirmatory investigations. [ABSTRACT FROM AUTHOR]

Purpose: The fluorescent in situ hybridization (FISH) technique, which easily detects reciprocal translocations, is currently used to estimate doses in retrospective biological dosimetry, after suspected accidental overexposure to ionizing radiation (IR). This study of 42 cases aimed to verify the appropriateness of this assay for radiation dose reconstruction, compared to the dicentric assay, and to evaluate other limitations. Material and methods: We labeled chromosomes 2, 4, and 12 by 3-color FISH painting to detect translocations on lymphocytes of patients with suspected past IR overexposure. Result: Translocation dose estimation showed doses significantly different from 0 Gy in 25 of the 42 cases. The lowest positive dose measured was 0.3 Gy. Several months after IR exposure, the doses measured by translocation and dicentric assays are quite similar. For a year, dose estimation by translocation assay becomes more relevant as dicentric frequency starts to decrease, coming close to 0 for more than a year after the exposure. The persistence of translocations enabled us to corroborate an overexposure 44 years earlier. Interpretation of the observed translocation yield requires the knowledge of the patient's other radiation exposures. A dose assessment by this biomarker is relevant only if the radiation exposure is confirmed. Conclusions: This technique is appropriate for corroborating a former IR exposure of individuals. When the radiation dose is greater than 1 Gy, the translocations in complex exchanges must be considered. Another relevant point is the use of an appropriate background yield of translocations. The dose assessment, however, also depends on exposure to various genotoxic agents besides IR. If no evidence about the existence of radiation exposure is available, dose assessment is not useful. For this reason, report only the translocation frequency and its comparison with the background yield by age class is preferable. [ABSTRACT FROM AUTHOR]

The article presents correction related to article published in periodical "International Journal of Radiation Biology" where it mentions that few more authors including Valeria Hadjidekova and Ljubomira Hadjiiska had to be acknowledged for their contribution to the research article.

Mueller matrices were measured for natural (or reference) samples of human nails and samples irradiated by a 2 Gy ionizing radiation dose. The elements of the total Mueller matrix as a function of scattering angle were measured in backscattering mode at a wavelength of 632.8 nm. Several types of depolarizing Mueller matrix decompositions, namely, Ossikovsky, Williams, and Chipman, were calculated as a function of scattering angle for each nail sample. A comparative analysis of the sensitivity of the Mueller matrix decompositions in relation to the problem of emergency dose assessment in nails was performed. [ABSTRACT FROM AUTHOR]

Purpose: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G0-lymphocyte PCC for harmonization, standardization and optimization of the PCC assay. Materials and methods: Comparative analysis among different partners for dose assessment included shipment of PCC-slides and captured images to construct dose-response curves for up to 6 Gy γ-rays. Accident simulation exercises were performed to assess the suitability of the PCC assay by detecting speed of analysis and minimum number of cells required for categorization of potentially exposed individuals. Results: Calibration data based on Giemsa-stained fragments in excess of 46 PCC were obtained by different partners using galleries of PCC images for each dose-point. Mean values derived from all scores yielded a linear dose-response with approximately 4 excess-fragments/cell/Gy. To unify scoring criteria, exercises were carried out using coded PCC-slides and/or coded irradiated blood samples. Analysis of samples received 24 h post-exposure was successfully performed using Giemsa staining (1 excess-fragment/cell/Gy) or centromere/telomere FISH-staining for dicentrics. Conclusions: Dose assessments by RENEB partners using appropriate calibration curves were mostly in good agreement. The PCC assay is quick and reliable for whole- or partial-body triage biodosimetry by scoring excess-fragments or dicentrics in G0-lymphocytes. Particularly, analysis of Giemsa-stained excess PCC-fragments is simple, inexpensive and its automation could increase throughput and scoring objectivity of the PCC assay. [ABSTRACT FROM AUTHOR]

Purpose:Two quality controlled inter-laboratory exercises were organized within the EU project ‘Realizing the European Network of Biodosimetry (RENEB)’ to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. Materials and methods:The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants. Results:The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. Conclusions:In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners. [ABSTRACT FROM PUBLISHER]

Purpose: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. Results: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. Conclusions: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects. [ABSTRACT FROM AUTHOR]

Purpose:To identify and assess, among the participants in the RENEB (Realizing the European Network of Biodosimetry) project, the emergency preparedness, response capabilities and resources that can be deployed in the event of a radiological or nuclear accident/incident affecting a large number of individuals. These capabilities include available biodosimetry techniques, infrastructure, human resources (existing trained staff), financial and organizational resources (including the role of national contact points and their articulation with other stakeholders in emergency response) as well as robust quality control/assurance systems. Materials and methods:A survey was prepared and sent to the RENEB partners in order to acquire information about the existing, operational techniques and infrastructure in the laboratories of the different RENEB countries and to assess the capacity of response in the event of radiological or nuclear accident involving mass casualties. The survey focused on several main areas: laboratory’s general information, country and staff involved in biological and physical dosimetry; retrospective assays used, the number of assays available per laboratory and other information related to biodosimetry and emergency preparedness. Following technical intercomparisons amongst RENEB members, an update of the survey was performed one year later concerning the staff and the available assays. Conclusions:The analysis of RENEB questionnaires allowed a detailed assessment of existing capacity of the RENEB network to respond to nuclear and radiological emergencies. This highlighted the key importance of international cooperation in order to guarantee an effective and timely response in the event of radiological or nuclear accidents involving a considerable number of casualties. The deployment of the scientific and technical capabilities existing within the RENEB network members seems mandatory, to help other countries with less or no capacity for biological or physical dosimetry, or countries overwhelmed in case of a radiological or nuclear accident involving a large number of individuals. [ABSTRACT FROM PUBLISHER]

Purpose: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. Materials and methods: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. Results: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. Conclusions: Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization. [ABSTRACT FROM AUTHOR]

Purpose: In the EC-funded project RENEB (Realizing the European Network in Biodosimetry), physical methods applied to fortuitous dosimetric materials are used to complement biological dosimetry, to increase dose assessment capacity for large-scale radiation/nuclear accidents. This paper describes the work performed to implement Optically Stimulated Luminescence (OSL) and Electron Paramagnetic Resonance (EPR) dosimetry techniques. Materials and methods: OSL is applied to electronic components and EPR to touch-screen glass from mobile phones. To implement these new approaches, several blind tests and inter-laboratory comparisons (ILC) were organized for each assay. Results: OSL systems have shown good performances. EPR systems also show good performance in controlled conditions, but ILC have also demonstrated that post-irradiation exposure to sunlight increases the complexity of the EPR signal analysis. Conclusions: Physically-based dosimetry techniques present high capacity, new possibilities for accident dosimetry, especially in the case of large-scale events. Some of the techniques applied can be considered as operational (e.g. OSL on Surface Mounting Devices [SMD]) and provide a large increase of measurement capacity for existing networks. Other techniques and devices currently undergoing validation or development in Europe could lead to considerable increases in the capacity of the RENEB accident dosimetry network. [ABSTRACT FROM AUTHOR]

Purpose: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network. Materials and methods: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples. A short survey was also performed to collect the information needed for the data analysis and evaluate the diversity of practices. Results: For most of partners the deviation of delivered dose from the targeted dose remains below 10%. Deviations larger than 10% were observed for five facilities out of 21. Origins of the largest discrepancies were identified. Correction actions were evaluated as satisfactory. The re-evaluation of some ILC results for the fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC) assays has been performed leading to an improvement of the overall performances. Conclusions: This work has shown the importance of dosimetry in radiobiology studies and the needs of harmonization, standardization in irradiation and dosimetry practices and educational training for biologists using ionizing radiation. [ABSTRACT FROM AUTHOR]

Purpose: Within the EU RENEB project, seven laboratories have taken part in training and harmonisation activities to strengthen triage gamma-H2AX-based radiation exposure assessment. This has culminated in a second triage biodosimetry exercise. Materials and methods: Whole blood and separated lymphocyte samples were homogenously irradiated with 60Co gamma rays at 0.5, 2.5 (blind samples), 0 and 2 Gy (reference samples). Following post-exposure incubations of 4 and 24 h, 16 samples were shipped on ice packs to each partner. The samples were stained and scored for gamma-H2AX foci, using manual and/or automated fluorescence microscope scoring strategies. Dose estimates were obtained and used to assign triage categories to the samples. Results: Average dose estimates across all the laboratories correlated well with true doses. The most accurate assignment of triage category was achieved by manual scoring of the 4-h blood and lymphocyte samples. Only three samples out of a total of 46 were miscategorized in a way that could have adversely effected the clinical management of a radiation casualty. Conclusions: This inter-comparison exercise has demonstrated that following a recent acute radiation exposure, the gamma-H2AX assay could be a useful triage tool that can be successfully applied across a network of laboratories. [ABSTRACT FROM AUTHOR]

Purpose:RENEB, ‘Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,’ is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods:The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation-induced thermoluminescent signals in glass screens taken from mobile phones. Results:In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions:Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios. [ABSTRACT FROM PUBLISHER]

Purpose:The European Network of Biological and Physical Retrospective Dosimetry ‘RENEB’ has contributed to European radiation emergency preparedness. To give homogeneous dose estimation results, RENEB partners must harmonize their processes. Materials and methods:A first inter-comparison focused on biological and physical dosimetry was used to detect the outliers in terms of dose estimation. Subsequently, trainings were organized to improve both tools dose estimation. A second inter-comparison was performed to validate training efficiency. Simultaneously, based on ISO standards, a QA&QM manual on all dosimetry assays was produced which states a common basis and harmonized procedures for each assay. The evaluation of the agreement of RENEB partners to follow the QA&QM manual was performed through a questionnaire. The integration of new members into the network was carried out in the same way, whatever the assays. Results:The training courses on biological and physical dosimetry were judged to be successful because most of the RENEB members’ dose estimates improved in the second inter-comparison. The QA&QM manual describes the consensus for the minimum requirements and the performance criteria for both dosimetry assays. The questionnaire revealed that the whole network capacity currently can manage between 15 and 3800 samples once. Conclusion:The methodology used to harmonize all dosimetry practice within the network RENEB was highly successful. The network is operational to manage a mass casualty radiation accident for immediate dose assessment. [ABSTRACT FROM PUBLISHER]

Purpose:In the framework of the ‘Realizing the European Network of Biodosimetry’ (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. Materials and methods:Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. Results:The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (≤ 0.94 Gy). For higher dose points (≥ 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. Conclusion:The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories. [ABSTRACT FROM PUBLISHER]

Purpose:To establish a training data set of digital images and to investigate the scoring criteria and dose assessment of the dicentric assay within the European network of biodosimetry (RENEB), a web based scoring inter-comparison was undertaken by 17 RENEB partners. Materials and methods:Two sets of 50 high resolution images were uploaded onto the RENEB website. One set included metaphases after a moderate exposure (1.3 Gy) and the other set consisted of metaphases after a high dose exposure (3.5 Gy). The laboratories used their own calibration curves for estimating doses based on observed aberration frequencies. Results:The dose estimations and 95% confidence limits were compared to the actual doses and the corresponding z-values were satisfactory for the majority; only the dose estimations from two laboratories were too low or too high. The coefficients of variation were 17.6% for the moderate and 11.2% for the high dose. Metaphases with controversial results could be identified for training purposes. Conclusions:Overall, the web based scoring of the two galleries by the 17 laboratories produced very good results. Application of web based scoring for the dicentric assay may therefore be a relevant strategy for an operational biodosimetry assistance network. [ABSTRACT FROM PUBLISHER]

Classical strength criteria, like the von Mises criterion, are used to postulate the failure of ductile materials like steel or brass. It is known that for the application of foams in modern lightweight structures extended criteria are required, since foams are sensitive to hydrostatic stress. This observation on the macroscale can be explained by the deformation mechanisms of one single foam cell. Under hydrostatic stress, the deformation of the cell causes a non-uniform stress state of the cell walls. To understand the mechanism on the microlevel, a finite element model on the basis of a tetrakaidecahedron as unit cell was implemented. Utilising a strain energy-based homogenisation concept, the effective properties of the foam can be obtained. To adapt the geometric properties of the model to the real microstructure of the foam, results of a computer tomography image analysis were used by considering several imperfections in the cell geometry. For the analysis of the stress state on the microlevel, different load cases were applied to the unit cell. By means of these simulations, the geometrically nonlinear stress-strain curves on the macrolevel were deduced. Furthermore, the analysis of the finite element model provides an insight into the deformation mechanism on the microscale and allows the prediction of failure as well. Finally, the predicted failure points are represented in the Burzyński plane and compared with experimental results. The current paper focuses on the hard foam ROHACELL $${^{\circledR}}$$ IG-series (industrial grade), which is a closed-cell PMI foam produced by Evonik Industries AG, Germany. [ABSTRACT FROM AUTHOR]

Dicentric chromosome analysis (DCA) is the gold standard for individual radiation dose estimation. Two limiting factors of DCA are the time-consuming lymphocyte stimulation and proliferation using the lectin PHA-M and the upper dose limit of individual dose assessment of ~4 Gy. By measuring the mitotic index (MI), the authors investigated systematically whether the stimulation of lymphocytes can be improved after administration of alternative (and combined) mitogens. The authors compared the lymphocyte stimulation effectiveness of the traditionally used PHA-M (from Phaseolus vulgaris) with seven cited mitogens by determination of MIs: five lectins namely CNA (concanavalin A), PW (pokeweed), LMA (Maackia amurensis), LTV (T. vulgaris), PHA-L (P. vulgaris) as well as LPS (lipopolysaccharide, Escherichia coli) and SLO (streptolysine O, Streptococcus pyogenes) were applied. The conventional protocol using PHA-M for lymphocyte stimulation proved to be superior over lower/higher PHA-M concentrations as well as seven other mitogens administered either alone or combined with SLO or LPS. [ABSTRACT FROM AUTHOR]

Neutropenic complications remain an important dose-limiting toxicity of cancer chemotherapy-associated with considerable morbidity, mortality, and cost. Risk of the initial neutropenic event is greatest during the first cycle. The purpose of this study was to better understand timing of neutropenic events in relation to delivered chemotherapy dose intensity and utilization of supportive care during cancer treatment. A prospective cohort study of adult patients with solid tumors or lymphoma initiating chemotherapy was conducted at 115 randomly selected US practice sites between 2002 and 2006. Chemotherapy-associated toxicities were captured in up to four treatment cycles including severe neutropenia, febrile neutropenia, and infection. Documented interventions included colony-stimulating factor ( CSF), antibiotics use, and reductions in chemotherapy relative dose intensity ( RDI). A total of 3638 patients with breast (39.7%), lung (23.7%), colorectal (13.6%), ovarian (8.3%) cancers, or lymphoma (14.7%) were eligible for this analysis. The majority of neutropenic and infection events occurred in the first cycle. A significant inverse relationship was observed between reductions in neutropenic and infectious events and increased utilization of measures to reduce these complications in subsequent cycles. More than 60% of patients with stage IV solid tumors underwent reductions in RDI. Patients with lymphoma and stage I-III solid tumors had less dose reductions while receiving more prophylactic CSFs. Approximately, 15% of patients received prophylactic antibiotics. While the risk of neutropenic complications remains greatest during the initial cycle of chemotherapy, subsequently instituted clinical measures in efforts to reduce the risk of these events vary with cancer type and stage. [ABSTRACT FROM AUTHOR]

The PDF file provided contains web links to all articles in this volume. [ABSTRACT FROM AUTHOR]

Background The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma. Methods Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics. Results 97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, with CBAVD being the reason for referral in 76%. In 166/ 179 patients with available detailed clinical features, final diagnoses were: four late-onset marked pulmonary disease, 83 isolated CBAVD, 67 other CFTR-related phenotypes, including 44 CBAVD with pulmonary and/or pancreatic symptoms and 12 asymptomatic cases. Respiratory symptoms were observed in 30% of the patients, but the overall phenotype was mild. No correlation was observed between sweat chloride concentrations and disease severity. Five couples at risk of CF offspring were identified and four benefited from prenatal or preimplantation genetic diagnoses (PND or PGD). Eight children were born, including four who were compound heterozygous for p.Arg117His and one with a severe CF mutation. Conclusions Patients with CBAVD carrying p.Arg117His and a severe CF mutation should benefit from a clinical evaluation and follow-up. Depending on the CBAVD patients' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD. [ABSTRACT FROM AUTHOR]

Background Little is known about the causes of death in human immunodeficiency virus (HIV)-infected women in the era of combination antiretroviral therapy (ART). [ABSTRACT FROM PUBLISHER]

Background: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. Methods: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (pR117H), on either intron 8 T5 or T7 background, and F508del (pF508del) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. Results: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, pF508del was 1.06%, pR117H;T7 0.27% and pR117H;T5<0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. Conclusions: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes. [ABSTRACT FROM AUTHOR]

Background. The goal of the current study was to describe the distribution and characteristics of malignancy-related deaths among human immunodeficiency virus (HIV)--infected patients with use of data obtained from a national survey conducted in France in 2005 and to compare with results obtained from a similar survey conducted in 2000. Method. The underlying cause of death was documented using a standardized questionnaire fulfilled in French hospital wards and networks that were involved in the treatment of HIV-infected patients. Results. Among the 1042 deaths reported in 2005 (964 were reported in 2000), 344 were cancer related (34%), which represented a significant increase from 2000 (29% of deaths were cancer related) (P=.02); 134 of the cancer-related deaths were AIDS related and 210 were not AIDS related. Among the cancer-related causes of death, the proportion of hepatitis-related cancers (6% in 2000 vs. 11% in 2005) and non-AIDS/hepatitis-related cancers (38% in 2000 vs 50% in 2005) significantly increased from 2000 to 2005 (P=.03 and P=.01, respectively), compared with the proportion of cancer that was AIDS related and adjusting for age and sex. Among cases involving AIDS, the proportion of non-Hodgkin lymphoma--associated deaths did not change statistically significantly between 2000 and 2005 (11% and 10% of deaths, respectively). Conclusions. In this study, an increasing proportion of lethal non--AIDS-related cancers was demonstrated from 2000 to 2005; meanwhile, the proportion of lethal AIDS-related cancers remained stable among HIV-infected patients. Thus, cancer prophylaxis, early diagnosis, and improved management should be included in the routine long-term follow-up of HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background: Bronchiectasis is defined as a permanent dilation of the airways arising from chronic bronchial inflammation/infection. In 50% of cases, no etiology can be identified. Recently, the role of the epithelial sodium channel ENaC has been pointed out in the pathophysiology of cystic fibrosis, a disease due to mutations in the CFTR gene and causing bronchiectasis in the airways. Moreover, it was found that transgenic mice overexpressing ENaC β present cystic fibrosis-like lung disease symptoms. Our aim was to evaluate if a defective ENaC protein could be involved in the development of bronchiectasis. Methods: We extensively analysed ENaC β and γ genes in 55 patients with idiopathic bronchiectasis and without two mutations in the coding regions of CFTR. Thirty-eight patients presented functional abnormalities suggesting impaired sodium transport (abnormal sweat chloride concentration or nasal potential difference measurement), and 17 had no such evidence. Results: Sequencing of the exons and flanking introns of the ENaC β and γ gene identified five different amino-acid changes (p.Ser82Cys, p.Pro369Thr, p.Asn288Ser in ENaC β ; and p.Gly183Ser, p.Glu197Lys in ENaC γ) in heterozygous state in 8 patients. The p.Ser82Cys amino-acid change was found in 3 unrelated patients who were also heterozygous for a CFTR mutation or variant (1 p.F508del, 1 IVS8-5T, and 1 IVS8-5T:1716G>A (p.E528E)). The other mutations were found in patients without CFTR mutation, the p.Glu197Lys mutation in 2 patients and the other variants in single patients. Among the 8 patients bearing an ENaC mutation, 5 had functional abnormalities suggesting impaired sodium transport. Conclusion: Our results suggest that several variants in ENaC β and γ genes might be deleterious for ENaC function and lead to bronchiectasis, especially in patients who are trans-heterozygotes for ENaC β/CFTR mutations or variants. [ABSTRACT FROM AUTHOR]

One of the goals of modern dynamic radiotherapy treatments is to deliver high-dose values in the shortest irradiation time possible. In such a context, fast X-ray detectors and reliable front-end readout electronics for beam diagnostics are crucial to meet the necessary quality assurance requirements of care plans. This work describes a diamond-based detection system able to acquire and process the dose delivered by every single pulse sourced by a linear accelerator (LINAC) generating 6-MV X-ray beams. The proposed system is able to measure the intensity of X-ray pulses in a limited integration period around each pulse, thus reducing the inaccuracy induced by unnecessarily long acquisition times. Detector sensitivity under 6-MV X-photons in the 0.1–10 Gy dose range was measured to be 302.2 nC/Gy at a bias voltage of 10 V. Pulse-by-pulse measurements returned a charge-per-pulse value of 84.68 pC, in excellent agreement with the value estimated (but not directly measured) with a commercial electrometer operating in a continuous integration mode. Significantly, by intrinsically holding the acquired signal, the proposed system enables signal processing even in the millisecond period between two consecutive pulses, thus allowing for effective real-time dose-per-pulse monitoring. [ABSTRACT FROM AUTHOR]

With the ever-increasing development in science and technology, as well as social awareness, more requirements are imposed on the production and property of all materials, especially polymeric foams. In particular, rubber foams, compared to thermoplastic foams in general, have higher flexibility, resistance to abrasion, energy absorption capabilities, strength-to-weight ratio and tensile strength leading to their widespread use in several applications such as thermal insulation, energy absorption, pressure sensors, absorbents, etc. To control the rubber foams microstructure leading to excellent physical and mechanical properties, two types of parameters play important roles. The first category is related to formulation including the rubber (type and grade), as well as the type and content of accelerators, fillers, and foaming agents. The second category is associated to processing parameters such as the processing method (injection, extrusion, compression, etc.), as well as different conditions related to foaming (temperature, pressure and number of stage) and curing (temperature, time and precuring time). This review presents the different parameters involved and discusses their effect on the morphological, physical, and mechanical properties of rubber foams. Although several studies have been published on rubber foams, very few papers reviewed the subject and compared the results available. In this review, the most recent works on rubber foams have been collected to provide a general overview on different types of rubber foams from their preparation to their final application. Detailed information on formulation, curing and foaming chemistry, production methods, morphology, properties, and applications is presented and discussed. [ABSTRACT FROM AUTHOR]

Following recent developments, the RENEB network (Running the European Network of biological dosimetry and physical retrospective dosimetry) is in an excellent position to carry out large scale molecular epidemiological studies of ionizing radiation effects, with validated expertise in the dicentric, fluorescent in situ hybridization (FISH)-translocation, micronucleus, premature chromosome condensation, gamma-H2AX foci and gene expression assays. Large scale human health effects studies present complex challenges such as the practical aspects of sample logistics, assay costs, effort, effect modifiers and quality control/assurance measures. At Public Health England, the dicentric, automated micronucleus and gamma-H2AX radiation-induced foci assays have been tested for use in a large health effects study. The results of the study and the experience gained in carrying out such a large scale investigation provide valuable information that could help minimise random and systematic errors in biomarker data sets for health surveillance analyses going forward. [ABSTRACT FROM AUTHOR]