1,720,971 research outputs found

    APPLICAZIONE DEI LIMITI DI LEGGE PER IL TASSO ALCOLEMICO: INTERPRETAZIONE ANALITICO-FORENSE LEGAL LIMITS FOR THE ALCOHOL RATE: ANALYTICAL-FORENSIC INTERPRETATION

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    Summary/Riassunto The aim of this work is to clarify some aspects that should allow an interpretation of the analytical data unique, shared and accepted by the community as obtained through statisticalmathematical tools (chemometric) essential in the expression and interpretation of any measurements. There is objectively a difficulty of communication between scientists and jurists when applying regulations involving the use of statistical and mathematical tools: literature is filled by several lawsuits resulting from this difficulty; it being understood the right of defense that a party has, however, you need to put a fundamental point on certain aspects (numeric, and therefore objective) that should not be matter for discussion anymore. Regarding the breathalyzer, it is already accepted the conversion constant between the concentration of ethanol in exhaled air and blood concentration: for such constant, regardless of how it can be scientifically shareable its interpretation, during a judicial procedure no objection is admissible. But, about the verification of exceeding the legal limits, are still needed to establish an indisputable method, which must take into account all the law prescriptions: both the established limits, both the measurement uncertainties associated with the breathalyzer. This paper aims to highlight how, once the analytical result expressed in the correct form (significant digits, uncertainty, etc.), you can beyond any reasonable doubt compare the limit values to express an objective and unequivocal judgment of compliance to the norm. Lo scopo della presente riflessione è chiarire alcuni aspetti che dovrebbero permettere un'interpretazione del dato analitico unica, condivisa e da tutti accettata in quanto ottenuta attraverso strumenti statistico-matematici (chemiometrici) essenziali nell'espressione ed interpretazione di qualsiasi misurazione tecnica. Esiste obiettivamente una difficoltà di comunicazione tra Scienziati e Giuristi quando si applicano normative che comportano l’uso di strumenti statistici e matematici: numerose cause derivanti da tale difficoltà riempiono la letteratura giudiziaria; fermo restando il diritto di difesa che una controparte ha, è necessario però porre un punto fermo su certi aspetti (numerici, e quindi oggettivi) che non dovrebbero più essere motivo di discussione. Nel caso dell’etilometro, si è già posto un punto fermo nell’utilizzo della costante di conversione tra concentrazione di etanolo nell’aria espirata e concentrazione nel sangue: per tale costante, indipendentemente da quanto possa essere scientificamente condivisibile una sua interpretazione, in sede dibattimentale non viene più ammessa alcuna contestazione. Ma per quanto riguarda la verifica del superamento dei limiti di legge c’è ancora bisogno di stabilire un metodo incontestabile, che deve tenere conto di tutte le indicazioni della legge: sia i limiti stabiliti, sia le incertezze di misura associate alle misure effettuate su persone soggette a controlli mediante etilometro. Nel presente lavoro si vuole mettere in luce come, una volta espresso il risultato analitico nella forma corretta (cifre significative, incertezza, etc.), si può oltre ogni ragionevole dubbio confrontarlo con i valori-limite per esprimere un oggettivo ed inequivocabile giudizio di conformità o meno alla norma

    Quantification of 108 illicit drugs and metabolites in bile matrix by LC–MS/MS for the toxicological testing of sudden death cases

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    Sudden death could occur after assumption of illicit drugs for recreational purposes in adults or after intoxication in children, and toxicological testing would help identify the cause of the death. Analytical methods sensitive and specific for the quantification of a great number of drugs and metabolites in at least 2 matrices should be used. Bile, collected postmortem, may be considered a specimen alternative to blood and urine to perform toxicological testing because of its extended detection window. The present study proposed a LC–MS/MS method to quantify 108 drugs and metabolites in bile. Compounds belonging to the drugs of abuse classes of amphetamines, benzodiazepines, cocaine derivatives, barbiturates, opioids, z-drugs, and psychedelics were analyzed. The sample preparation is simple and does not require solid-phase extraction. The proposed method showed an appropriate selectivity, specificity, accuracy, and precision of the calibrators and quality controls tested (precision < 15%; accuracy < 100 ± 15%). The sensitivity allowed to identify low amounts of drugs (e.g., morphine limit of detection = 0.2 μg/L; limit of quantification = 1.1 μg/L). There is no significant matrix effect, except for buprenorphine and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol. Carry-over was not present. Analytes were stable at least for 1 month at − 20 °C. Analyzing 13 postmortem specimens, methadone (50%), and cocaine (37.5%) resulted to be the most prevalent consumed substances; the concentrations quantified in bile resulted to be higher than the ones in blood suggesting bile as a potential new matrix for identifying illicit drugs and their metabolites

    Simultaneous multi-targeted forensic toxicological screening in biological matrices by MRM-IDA-EPI mode

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    The toxicologist ascertains drug assumptions in case of paediatric intoxications and death for overdose. The analytical approach consists of initially screening and consequently confirming drug positivity. We developed a toxicological screening method and validated its use comparing the results with a LC-MS/MS analysis. The method identifies 751 drugs and metabolites (704 in positive and 47 in negative mode). Chromatographic separation was achieved eluting mobile phase A (10 mM ammonium formate) and B (0.05% formic acid in methanol) in gradient on Kinetex Phenyl-Hexyl (50 × 4.6 mm, 2.6 μm) with 0.7 mL/min flow rate for 11 min. Multiple Reaction Monitoring (MRM) was adopted as survey scan and, after an Information-Dependent Analysis (IDA) (threshold of 30,000 for positive and 1000 cps for negative mode), the Enhanced Product Ion (scan range: 50-700 amu) was triggered. The MS/MS spectrum generated was compared with one of the libraries for identification. Data processing was optimised through creation of rules. Sample preparation, mainly consisting of deproteinization and enzymatic hydrolysis, was set up for different matrices (blood, urine, vitreous humor, synovial fluid, cadaveric tissues and larvae). Cut-off for most analytes resulted in the lowest concentration tested. When the results from the screening and LC-MS/MS analysis were compared, an optimal percentage of agreement (100%) was assessed for all matrices. Method applicability was evaluated on real paediatric intoxications and forensic cases. In conclusion, we proposed a multi-targeted, fast, sensitive and specific MRM-IDA-EPI screening having an extensive use in different toxicological fields

    A new proof of evidence of cysteamine quantification for therapeutic drug monitoring in patients with cystinosis

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    BACKGROUND: To date, measurement of intracellular cystine is used for the therapeutic monitoring of patients affected by cystinosis in treatment with cysteamine. Since this method is time and sample consuming, development of a faster method to quantify cysteamine would be extremely useful in order to help clinicians to adjust dosages of cysteamine and to define better the pharmacokinetic profile of this drug. The aim of the study was to develop a liquid chromatography tandem mass spectrometry method for the quantification of cysteamine in plasma samples and to test its applicability on plasma samples derived from patients with nephropathic infantile cystinosis in treatment with cysteamine. RESULTS: The percentage of accuracy of the developed method varied between 97.80 and 106.00% and CV% between 0.90 and 6.93%. There was no carry over. The calibration curves were built from 2.5 to 50 µM. The limit of detection and the lower limit of quantification occurred at 0.25 and 1.25 µM respectively. Cysteamine was stable up to 2 months at -20 °C. Concentrations of cysteamine and intracellular cystine of 4 patients were in line with data previously reported. CONCLUSION: The proposed method showed an appropriate selectivity, specificity, linearity, sensibility, accuracy, precision and good applicability to samples

    Applicability of a Chemiluminescence Immunoassay to Screen Postmortem Bile Specimens and Its Agreement with Confirmation Analysis

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    Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis. Bile specimens were obtained from 25 forensic cases of suspected death from overdose and intoxication. Sample preparation for bile screening consists simply in centrifugation and dilution. Confirmation analysis allows simultaneous identification of 108 drugs and was validated on bile. Kappa analysis assessed a perfect agreement (0.81–1) between the assays for benzodiazepines, methadone, opiates, cocaine, oxycodone, cannabinoids, buprenorphine and pregabalin; a substantial agreement (0.41–0.6) was reported for barbiturates. No agreement was assessed for amphetamines, due to an abundance of putrefactive amines in postmortem specimens. In conclusion, this fast and easy immunoassay could be used for initial screening of bile specimens, identifying presence of drugs, except amphetamines, with reliability

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Metabolomics biomarkers of frailty in elderly breast cancer patients

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    Metabolome analysis has emerged as a powerful technique for detecting and define specific physio-pathological phenotypes. In this investigation the diagnostic potential of metabolomics has been applied to better characterize the multiple biochemical alterations that concur in the definition of the frailty phenotype observed in elderly breast cancer patients. The study included 89 women with breast cancer (range 70-97 years) classified as Fit (n=49), Unfit (n=23), or Frail (n=17) according to comprehensive geriatric assessment. The serum metabolomic profile was performed by tandem mass spectrometry and included different classes of metabolites such as amino acids, acylcarnitines, sphingo-, and glycerol-phospolipids. ANOVA was applied to identify the metabolites differing significantly among Fit, Unfit, and Frail patients. In patients carrying the frail phenotype, the amino acid perturbations involve serine, tryptophan, hydroxyproline, histidine, its derivate 3-methyl-hystidine, cystine, and β-aminoisobutyric acid. With regard to lipid metabolism, the frailty phenotype was characterized by a decrease of a wide number of glycerol- and sphingo-phospholipid metabolites. These metabolomics biomarkers may give a further insight into the biochemical processes involved in the development of frailty in breast cancer patients. Moreover, they might be useful to refine the comprehensive geriatric assessment model. J. Cell. Physiol. 229: 898-902, 2014. © 2013 Wiley Periodicals, Inc

    Stability of a novel Lidocaine, Adrenaline and Tetracaine sterile thermosensitive gel: A ready-to-use formulation

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    BACKGROUND: Superficial wounds that require suturing are often the reason children visit the Paediatric Emergency Department. Suturing is usually accompanied by perilesional administration of lidocaine, a local anaesthetic drug that improves pain tolerance. In paediatric patients, this approach has a low compliance because lidocaine has to be injected, which in children generates fear and anxiety, a sterile anaesthetic gel could improve the child compliance. OBJECTIVE: To develop a sterile and stable sterile gel capable of remaining in place over time for topical anaesthesia. METHOD: Different formulations were analysed by HPLC, by UV and fluorimetric detection. Two different sterilisation methods were tested. MAIN OUTCOME: To maintain the original stability of the gel also after sterilisation process. RESULTS: Four different gels were prepared and analysed; the most stable gel lasts over 3 months with a degradation less than 10%. CONCLUSION: The use of Poloxamer 407 guarantees stability of the preparation, showing a reduction in oxidative reaction, and gives the gel the right texture for application to a bleeding wound

    Identification of 5F-Cumyl-PINACA, a Synthetic Cannabinoid, in the Herbal Material Used for Recreational Purposes in the Province of Trieste: Public Health Implications

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    In recent years, the phenomenon of the production and trade of synthetic cannabinoids has grown, becoming a public health issue worldwide. The recent accesses - to the ED of the hospital of Trieste - of people who complained episodes of hallucinations, sensation of poisoning, tachycardia, and air hunger following the inhalation of "Che Sballo platinum", have highlighted the need to perform further analysis on the contents of the packet sold as an air freshener, produced in Koper (Slovenia)
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