A review of the analytical techniques for the detection of anabolic–androgenic steroids within biological matrices

Anabolic–androgenic steroids (AASs) and other image and performance enhancing drugs (IPEDs) are controlled by governments and sport institutions such as the World Anti-doping Agency (WADA). Although elite athletes and professional bodybuilders are the most visible AAS abusers, the introduction of the internet has increased the accessibility of AASs, with use being observed among recreational gym goers at increasing prevalence. Despite reported increase in use, routine analysis for these substances is uncommon, with many forensic laboratories opting to outsource AAS analysis. This review collates information regarding the extraction and analysis of AASs from various biological matrices with the considered purpose of providing a reference for the development of AAS methods to allow for routine detection by forensic laboratories

Postmortem tissue distribution of morphine and its metabolites in a series of heroin related deaths

The abuse of heroin (diamorphine) and heroin deaths are growing around the world. The interpretation of the toxicological results from suspected heroin deaths is notoriously difficult especially in cases where there may be limited samples. In order to help forensic practitioners with heroin interpretation we determined the concentration of morphine (M), morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G) in blood (femoral and cardiac), brain (thalamus), liver (deep right lobe), bone marrow (sternum), skeletal muscle (psoas) and vitreous humor in 44 heroin related deaths. The presence of 6‐monoacetylmorphine (6‐MAM) in any of the postmortem samples was used as confirmation of heroin use. Quantitation was carried out using a validated LC‐MS/MS method with solid phase extraction. We also determined the presence of papaverine, noscapine and codeine in the samples, substances often found in illicit heroin and that may help determine illicit heroin use. The results of this study show that vitreous is the best sample to detect 6‐MAM (100% of cases), and thus heroin use. The results of the M, M3G and M6G quantitation in this study allow a degree of interpretation when samples are limited. However in some cases it may not be possible to determine heroin/morphine use as in 4 cases in muscle (3 cases in bone marrow) no morphine, morphine‐3‐glucuronide or morphine‐6‐glucuronide was detected, even though they were detected in other case samples. As always postmortem cases of suspected morphine/heroin intoxication should be interpreted with care and with as much case knowledge as possible

Learning from remote decentralised clinical trial experiences:a qualitative analysis of interviews with trial personnel, patient representatives and other stakeholders

AIMS: The aim of the study was to identify actionable learning points from stakeholders in remote decentralised clinical trials (RDCTs) to inform their future design and conduct. METHODS: Semistructured interviews were carried out with a purposive sample of stakeholders, including senior managers, trial managers, technology experts, principal investigators, clinical investigators, research scientists, research nurses, vendors, patient representatives and project assistants. The interview data were coded using a thematic approach, identifying similarities, differences and clustering to generate descriptive themes. Further refinement of themes was guided by empirical phenomenology, grounding explanation in the meanings that interviewees gave to their experiences. RESULTS: Forty‐eight stakeholders were interviewed. Actionable learning points were generated from the thematic analysis. Patient involvement and participant engagement were seen as critical to the success of RDCTs where in‐person contact is minimal or nonexistent. Involving patients in identifying the research question, creating recruitment materials, apps and websites, and providing ongoing feedback to trial participants were regarded as facilitating recruitment and engagement. Building strong relationships early with trial partners was thought to support RDCT conduct. Multiple modes of capturing information, including patient‐reported outcomes (PROs) and routinely collected data, were felt to contribute to data completeness. However, RDCTs may transfer trial activity burden onto participants and remote‐working research staff, therefore additional support may be needed. CONCLUSION: RDCTs will continue to face challenges in implementing novel technologies. However, maximising patient and partner involvement, reducing participant and staff burden, and simplifying how participants and staff interact with the RDCT may facilitate their implementation

From Inception to ConcePTION: Genesis of a Network to Support Better Monitoring and Communication of Medication Safety During Pregnancy and Breastfeeding

In 2019, the Innovative Medicines Initiative (IMI) funded the ConcePTION project—Building an ecosystem for better monitoring and communicating safety of medicines use in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation—with the vision that there is a societal obligation to rapidly reduce uncertainty about the safety of medication use in pregnancy and breastfeeding. The present paper introduces the set of concepts used to describe the European data sources involved in the ConcePTION project and illustrates the ConcePTION Common Data Model (CDM), which serves as the keystone of the federated ConcePTION network. Based on data availability and content analysis of 21 European data sources, the ConcePTION CDM has been structured with six tables designed to capture data from routine healthcare, three tables for data from public health surveillance activities, three curated tables for derived data on population (e.g., observation time and mother-child linkage), plus four metadata tables. By its first anniversary, the ConcePTION CDM has enabled 13 data sources to run common scripts to contribute to major European projects, demonstrating its capacity to facilitate effective and transparent deployment of distributed analytics, and its potential to address questions about utilization, effectiveness, and safety of medicines in special populations, including during pregnancy and breastfeeding, and, more broadly, in the general population

Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans

T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines

Forensic toxicology applications of capillary electrophoresis (CE) coupled to electrospray ionization (ESI) time of flight (TOF) mass spectrometry

Non disponibileForensic science includes all the applications of science which can be used to support at any level the enforcement of the law. Moreover in many countries the term forensic science also includes the scientific knowledge on the basis of which news laws and rules are drafted (Tagliaro, 2006). Just limiting the attention to the analytical aspects of forensic science, an extremely wide application area is thus identified, including forensic toxicology, personal identification, identification of gunshot and postblast residues, investigation of the cause of fatal intoxications, fire and arson investigation, analysis of fibers and hairs, analysis of inks and paints, etc. Nowadays, classical analytical techniques such as gas chromatography (GC) or high performance liquid chromatography (HPLC), capillary electrophoresis (CE) has been used in the field of forensic analysis. In many new laboratories work has been started to explore the potential of CE and numerous application were published (Thormann, 2001). It is well known that Capillary Electrophoresis (CE) is the most powerful techniques for the separation of charged analytes, which, in principle, pose problems to both HPLC and GC. CE analyte separation, normally carried out in fused silica capillaries, is based on the different rates of migration of charged molecules in a buffer solution under the influence of an electrical field, which also generates an electroosmotic flow (EOF). Since longitudinal molecular diffusion and mass transfer restrictions encountered in liquid chromatography (LC) are not relevant in CE, the mass sensitivity and separation efficiency of CE is significantly better than LC. Moreover the use of mass spectrometry as detector for CE has increasingly gained acceptance, complementing or replacing conventional detection methods such as UV absorbance, electrochemical oxidation/reduction or fluorescence, which are less informative and also less universal. Over the past few years, considerable advances have been made in the development of interfaces, thus facilitating the transfer of analytes from the liquid phase of CE separation to the gas phase of MS analysis. Areas of still active research in CE include CZE, chiral separations, micellar electrokinetic capillary chromatography (MEKC), nonacqueous capillary electrophoresis (NACE), CE with chemiluminescence detection, capillary electrophoresis mass spectrometry (CE-MS), capillary electrochromatography (CEC) and \u201cCE on a chip\u201d technology. On the other hand, numerous applications using CE and CE-MS, clearly indicate that this technique CE is going to become a routine tool for the analysis of seized drugs, explosive analysis and gunshot residues, small ions of forensic interest, forensic DNA and RNA analysis, protein of forensic interest, ink analysis. A brief summary of CE and CE-MS applications to forensic drug analysis recently reported in the literature is presented below

Gruppo elettrogeno fotovoltaico portatile

Oggetto del brevetto è un generatore solare portatile pensato per fornire energia in zone non fornite da reti elettriche. Il sistema è caratterizzato leggerezza e semplicità di messa in funzione, consente di alimentare telefoni portatili, pc e piccoli elettrodomestici

Carbohydrate-deficient transferrin (CDT) as a marker of alcohol abuse:a critical review of the literature 2001-2005

The diagnosis of alcohol abuse based on objective data is a necessary requirement in both clinical and forensic environments. Among the different biomarkers of chronic alcohol abuse, carbohydrate-deficient transferrin (CDT) is world wide recognized as the most reliable indicator.However, several problems about the real meaning of CDT and the reliability of its use for the diagnosis of alcohol abuses are still open, as reported by numerous research articles and reviews. The present article presents a critical review of the literature on CDT appeared in the period from2001 to 2005 (included). The article is organized in the following sections: (1) introduction, (2) definition and structure of human serum CDT, (3) pathomechanisms of the ethanol-induced CDT increase, (4) preanalysis, (5) analysis, (6) data interpretation, (7) review papers, (8) conclusions. As many as 127 papers appeared in the international literature and retrieved by the search engines PubMed and Scopus are quoted