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An interlaboratory evaluation of a chemical profiling method for a nerve agent precursor was performed by eight chemical analytical laboratories with a wide global distribution. A set of chemical attribution signatures (i.e. impurities) present in methylphosphonic dichloride (DC) were analysed by gas chromatography-mass spectrometry (GC/MS). The GC/MS analyses were performed with the individual instrumentation and analytical methods used by the laboratories in proficiency tests organized by the Organisation for the Prohibition of Chemical Weapons (OPCW). Two batches of DC, produced by two different production routes, were dispatched together with one reference sample. By the use of a targeted MS-library, sixteen chemical attribution signatures were analysed in the DC samples. Retention indices, mass spectra and relative peak areas of the GC/MS data were evaluated. When the within batch-data of the eight laboratories were compared, similarity values of 0.720-0.995 were obtained. In addition, the two different batches had clearly unique chemical attribution profiles, as indicated by a large between batch-distance similarity values of 0.509-0.576. Retention indices showed less than +/- 14 retention index unit variation for the 16 chemical attribution signatures. This study showed the potential of getting consistent chemical profiling data over multiple laboratories by the use of retention indices for alignment of GC/MS-data. The results indicate that the GC/MS instrumentation and methods used at most OPCW designated laboratories are valid tools for the acquisition of chemical profiling data of importance for the attribution analysis to study suspected production or use of chemical warfare agents.

Although chemical warfare agents (CWAs) are prohibited under international law, there have been numerous crimes that violates the 1997 Chemical Weapons Convention (CWC) during the last decade, especially in the civil war in Syria where sarin, mustard gas and chlorine have all been used. CWAs have also been used in political assassinations and attempts thereof. In such situations, it is important to identify the deployed CWA and to find information on how it was produced, as this information is potentially of considerable value for any ensuing judicial process. The development and use of advanced analytical methods and multivariate data analysis methods are required to produce this kind of robust forensic evidence and intelligence. This thesis describes conducted research that aims at retrospectively tracing the synthesis methods applied in the production of CWAs. In three studies, methods for the determination of the employed synthetic route have been assessed. The relative distribution of the impurities gave a unique profile – in effect a “chemical fingerprint” - that was used for retrospective determination of the production method of a specific CWA. The study in paper I was done on the nerve agent Russian VX, S-[2-(diethylamino)ethyl] O-isobutyl metylphosphonothioate, while paper II and III focused on sulfur mustard, bis(2-chloroethyl)sulfide. This thesis discusses the study set up, the choice of analytical methods, methods for data processing and the manner in which classification methods have been employed. The studies shows that the classification models could clearly separate the six production routes used in paper I and the five routes used in paper II. In paper III, a novel non-targeted approach in combination with high-resolution mass spectrometry allowed detection of additional low-concentration compounds in the sulfur mustard samples. This method produced data with sufficient information for classifying samples according to the production method of th, 2022-11-02: ISBN (PDF) has been corrected in the E-version.Funding agencies: FOI

Bakgrund: Alla diabetiker erbjuds screening av ögonbottnen för diabetesretinopati så att den ska kunna upptäckas och behandlas i tid. Enligt Region Skånes riktlinje för screening av diabetesretinopati kan en traditionell funduskamera eller en wide field ka-mera som täcker 80 procent av näthinnan användas, något som hittills enbart Optos kan. Syftet med studien var att undersöka hälso- och sjukvårdspersonalens uppfattningar om Optos i samband med screening av diabetesretinopati. Metod: Femton ögonmottagningar visade sig använda Optos. Av dessa deltog tio i tvär-snittsenkätstudien. En webbenkät utformades bestående av öppna och multiple-choice frågor. Fritextsvaren analyserades med innehållsanalys som resulterade i ett antal kategorier och respektive svarsfrekvenser. Resultat: Optos uppfattades som en användar- och patientvänlig metod vilken kan öka tillgängligheten. Skärpan i Optomap uppfattades vara god, men något sämre än i fun-dusbilderna. Några uppfattade Optos som en bra metod för screening av diabetesretino-pati. Andra ansåg att användning av Optos skulle innebära en patientrisk. Då den sämre centrala skärpan skulle kunna leda till underdiagnosticering alternativt att Optomaps stora täckningsgrad skulle kunna vara anledning till en överdiagnosticering. Ett stort externt bortfall begränsar studieresultatets generaliserbarhet. Slutsats: Uppfattningar huruvida Optos anses vara lämpligt att användas i samband med screening av diabetesretinopati går isär och lämpliga användningsområden behöver definieras närmare., Background: Screening for retinopathy is offered to all diabetics to allow detection and treatment on time. According to a regional guideline for screening of diabetic retino-pathy traditional fundus camera may be used or a wide field camera picturing 80 % of the retina, something nowadays only Optos can do. Aim of this study was to investigate health personnel’s attitude towards Optos in the context of diabetic retinopathy screening. Methods: Fifteen eye clinics using Optos were identified and ten of those took part in this survey. Self-administered questionnaires with multiple-choice and open questions were used. Free text answers were analysed using context analysis with determination of frequencies for the evolving categories. Results: Optos was perceived as being user and patient friendly, as well as being able to increase accessibility. Optomap had good but digital fundus pictures better perceived acuity. According to some was Optos a good method for screening of diabetic retino-pathy and inappropriate according to others apprehending a patient risk. Expecting underdiagnosis due to less central acuity alternatively overdiagnosis due to Optomap covering 80 % of the retina. High drop-out rate eventuates limited validity. Conclusions: Diverging attitudes emerged whether Optos is suitable for screening of diabetic retinopathy. Its appropriate use needs to be defined in further detail.

Route determination of sulfur mustard was accomplished through comprehensive nontargeted screening of chemical attribution signatures. Sulfur mustard samples prepared via 11 different synthetic routes were analyzed using gas chromatography/high-resolution mass spectrometry. A large number of compounds were detected, and multivariate data analysis of the mass spectrometric results enabled the discovery of route-specific signature profiles. The performance of two supervised machine learning algorithms for retrospective synthetic route attribution, orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF), were compared using external test sets. Complete classification accuracy was achieved for test set samples (2/2 and 9/9) by using classification models to resolve the one-step routes starting from ethylene and the thiodiglycol chlorination methods used in the two-step routes. Retrospective determination of initial thiodiglycol synthesis methods in sulfur mustard samples, following chlorination, was more difficult. Nevertheless, the large number of markers detected using the nontargeted methodology enabled correct assignment of 5/9 test set samples using OPLS-DA and 8/9 using RF. RF was also used to construct an 11-class model with a total classification accuracy of 10/11. The developed methods were further evaluated by classifying sulfur mustard spiked into soil and textile matrix samples. Due to matrix effects and the low spiking level (0.05% w/w), route determination was more challenging in these cases. Nevertheless, acceptable classification performance was achieved during external test set validation: chlorination methods were correctly classified for 12/18 and 11/15 in spiked soil and textile samples, respectively., Funding agencies: This work was funded by the Swedish Ministry of Defence and the Swedish Civil Contingencies Agency

Chemical attribution signatures (CAS) associated with different synthetic routes used for the production of Russian VX (VR) were identified. The goal of the study was to retrospectively determine the production method employed for an unknown VR sample. Six different production methods were evaluated, carefully chosen to include established synthetic routes used in the past for large scale production of the agent, routes involving general phosphorus-sulfur chemistry pathways leading to the agent, and routes whose main characteristic is their innate simplicity in execution. Two laboratories worked in parallel and synthesized a total of 37 batches of VR via the six synthetic routes following predefined synthesis protocols. The chemical composition of impurities and byproducts in each route was analyzed by GC/MS-EI and 49 potential CAS were recognized as important markers in distinguishing these routes using Principal Component Analysis (PCA). The 49 potential CAS included expected species based on knowledge of reaction conditions and pathways but also several novel compounds that were fully identified and characterized by a combined analysis that included MS-CI, MS-EI and HR-MS. The CAS profiles of the calibration set were then analyzed using partial least squares discriminant analysis (PLS-DA) and a cross validated model was constructed. The model allowed the correct classification of an external test set without any misclassifications, demonstrating the utility of this methodology for attributing VR samples to a particular production method. This work is part one of a three-part series in this Forensic VSI issue of a Sweden-United States collaborative effort towards the understanding of the CAS of VR in diverse batches and matrices. This part focuses on the CAS in synthesized batches of crude VR and in the following two parts of the series the influence of food matrices on the CAS profiles are investigated., Funding agencies: the Swedish Civil Contingencies Agency (under Contract 2014–5170) and the Department of Homeland Security, Science and Technology Directorate, Chemical Forensic Program (under Contract # HSHQPM-10-X-00014 and HSHQPM-11-X-00247), United States