452 results on '"Franco Taroni"'
Search Results
202. Probabilistic age classification with Bayesian networks: A study on the ossification status of the medial clavicular epiphysis
- Author
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Franco Taroni, Vilma Pinchi, and Emanuele Sironi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Computer science ,Bayesian probability ,Context (language use) ,Sample (statistics) ,Scientific literature ,Machine learning ,computer.software_genre ,01 natural sciences ,Pathology and Forensic Medicine ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Osteogenesis ,Age Determination by Skeleton ,medicine ,Humans ,030216 legal & forensic medicine ,Child ,Models, Statistical ,business.industry ,010401 analytical chemistry ,Probabilistic logic ,Bayesian network ,Bayes Theorem ,Clavicle ,0104 chemical sciences ,Test (assessment) ,Surgery ,Identification (information) ,Child, Preschool ,Forensic Anthropology ,Female ,Artificial intelligence ,business ,Law ,computer ,Epiphyses - Abstract
In the past few decades, the rise of criminal, civil and asylum cases involving young people lacking valid identification documents has generated an increase in the demand of age estimation. The chronological age or the probability that an individual is older or younger than a given age threshold are generally estimated by means of some statistical methods based on observations performed on specific physical attributes. Among these statistical methods, those developed in the Bayesian framework allow users to provide coherent and transparent assignments which fulfill forensic and medico-legal purposes. The application of the Bayesian approach is facilitated by using probabilistic graphical tools, such as Bayesian networks. The aim of this work is to test the performances of the Bayesian network for age estimation recently presented in scientific literature in classifying individuals as older or younger than 18 years of age. For these exploratory analyses, a sample related to the ossification status of the medial clavicular epiphysis available in scientific literature was used. Results obtained in the classification are promising: in the criminal context, the Bayesian network achieved, on the average, a rate of correct classifications of approximatively 97%, whilst in the civil context, the rate is, on the average, close to the 88%. These results encourage the continuation of the development and the testing of the method in order to support its practical application in casework.
- Published
- 2015
203. Contributors
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Nicholas Ah Mew, Wado Akamatsu, Hasan Orhan Akman, Koji Aoyama, W. David Arnold, Rafael Artuch, Robert M. Bachoo, Sergio E. Baranzini, Michael Beck, Merrill D. Benson, Vladimir M. Berginer, Gerard T. Berry, Kevin M. Biglan, Thomas D. Bird, D. Montgomery Bissell, Michael H. Bloch, Aldobrando Broccolini, Robert H. Brown, Allison Caban-Holt, Brenda Canine, C. Thomas Caskey, Patrick F. Chinnery, David T. Chuang, Jacinta L. Chuang, Bernard A. Cohen, Anne M. Comi, Rody P. Cox, John C. Crabbe, Marie Y. Davis, Darryl C. De Vivo, Robert J. Desnick, Stefano Di Donato, Salvatore DiMauro, Michael M. Dowling, David A. Dyment, Florian S. Eichler, Ramyiadarsini Elangovan, Bernice Elger, Sara Elrefai, Orna Elroy-Stein, Bakri H. Elsheikh, Andrew G. Engel, Patricia Evans, Stanley Fahn, Scott C. Fears, John K. Fink, Theodore Friedmann, Martin J. Gallagher, Àngels García-Cazorla, Jill S. Goldman, Sailaja Golla, Sidney M. Gospe, William D. Graf, Robert C. Griggs, Andrea L. Gropman, Yian Gu, Teresa M. Gunn, David H. Gutmann, Richard Haas, Randi J. Hagerman, Matti J. Haltia, Emma B. Hare, Tamar Harel, Stephen L. Hauser, Elizabeth Head, James E. Hilbert, Eric P. Hoffman, Othon Iliopoulos, Hiroyuki Ishiura, Monica P. Islam, Clifford R. Jack, William G. Johnson, Fabrice Jotterand, Heinz Jungbluth, John P. Kane, Clara van Karnebeek, Saima N. Kayani, Pravin Khemani, Fenella J. Kirkham, A. Yasmine Kirkorian, John T. Kissel, Christine Klein, Kleopas A. Kleopa, Satoshi Kono, Michael C. Kruer, Walter A. Kukull, Jessica B. Lennington, David A. Lewis, Wen-Chen Liang, Katja Lohmann, Paul J. Lombroso, Reymundo Lozano, James R. Lupski, Paola Luzi, Qian Ma, Robert L. Macdonald, Gustavo H.B. Maegawa, Elizabeth A. Maher, Mary J. Malloy, Ami K. Mankodi, Douglas A. Marchek, Isaac Marin-Valencia, Frederick J. Marshall, James A. Mastrianni, Reuben Matalon, Richard Mayeux, Jennifer L. McCurdy, Andrew J. McGarry, John H. Menkes, Giovanni Meola, Ana Metelo, Kimberlee Michals Matalon, Bruce L. Miller, Massimiliano Mirabella, Justin Miron, Jun Mitsui, Hiroaki Miyajima, Shuki Mizutani, Sara E. Mole, Lisa M. Monteggia, Hugo W. Moser, Mary Ann Morris, Richard T. Moxley, Jennifer M. Mueller, Francesco Muntoni, Melissa E. Murray, Toshio Nakaki, Charles B. Nemeroff, Ichizo Nishino, William L. Nyhan, Hideyuki Okano, Jorge R. Oksenberg, Adam P. Ostendorf, Massimo Pandolfo, Maria Belen Pappa, Carmen Paradas, Juan M. Pascual, Gregory M. Pastores, Shailendra B. Patel, Marc C. Patterson, Davut Pehlivan, Scott D. Philibin, Cynthia Picard, Judes Poirier, Louis J. Ptáček, Geetha L. Radhakrishnan, Jeffrey W. Ralph, Sreeram V. Ramagopalan, Gerald V. Raymond, William Renthal, Victor I. Reus, E. Steve Roach, Roger N. Rosenberg, David S. Rosenblatt, Gerald Salen, Konrad Sandhoff, Lawrence D. Scahill, Steven S. Scherer, Raphael Schiffmann, Detlev Schindler, Frederick Schmitt, Susanne A. Schneider, Eric A. Schon, Edward H. Schuchman, Nicole Schupf, Margretta Reed Seashore, Dennis J. Selkoe, Caroline Sewry, Michael Shevell, Shunichiro Shinagawa, Jemeen Sreedharan, Myriam Srour, Kazuma Sugie, Kristen L. Szabla, Steven T. Szabo, Gábor Szuhay, Franco Taroni, Rabi Tawil, Mireia Tondo, Shoji Tsuji, Bjarne Udd, Wendy R. Uhlmann, Flora M. Vaccarino, Prashanthi Vemuri, Charles P. Venditti, David W. Volk, Dong Wang, David Watkins, David A. Wenger, Charles A. Williams, Kathleen S. Wilson, Golder N. Wilson, Barry Wolf, R. Max Wynn, and Shihui Yu
- Published
- 2015
204. Ataxias and Cerebellar Degenerations
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Caterina Mariotti and Franco Taroni
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congenital, hereditary, and neonatal diseases and abnormalities ,Cerebellum ,Spinocerebellar tract ,business.industry ,Degeneration (medical) ,Impaired coordination ,medicine.disease ,nervous system diseases ,medicine.anatomical_structure ,nervous system ,medicine ,Spinocerebellar ataxia ,business ,Neuroscience - Abstract
Ataxias are heterogeneous disorders characterized by impaired coordination in voluntary movements. They are more frequently caused by degeneration of cerebellar structures and spinocerebellar tracts.
- Published
- 2015
205. Disorders of Lipid Metabolism
- Author
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Stefano Di Donato and Franco Taroni
- Subjects
medicine.medical_specialty ,Newborn screening ,Myoglobinuria ,Encephalopathy ,Cardiomyopathy ,Lipid metabolism ,Biology ,medicine.disease ,Bioinformatics ,Endocrinology ,Peripheral neuropathy ,Internal medicine ,medicine ,medicine.symptom ,Myopathy ,Rhabdomyolysis - Abstract
Inherited defects in mitochondrial fatty-acid β-oxidation comprise a group of at least 18 autosomal recessive disorders characterized by distinct enzyme or transporter deficiencies that represent most of the biochemical steps in the pathway. They manifest with a spectrum of clinical phenotypes, including progressive lipid storage myopathy, rhabdomyolysis with paroxysmal myoglobinuria, peripheral neuropathy, progressive cardiomyopathy, hypoglycemic hypoketotic encephalopathy, seizures, and mental retardation. They are potentially rapidly fatal and a source of major morbidity. Early recognition and prompt institution of therapy and appropriate preventive measures may be life-saving and may significantly decrease long-term morbidity, including CNS sequelae. The diagnosis is based on finding accumulation of specific biochemical markers such as acylcarnitines in blood and urinary dicarboxylic acids and acylglycines. Confirmatory testing requires enzymatic studies and DNA analysis. Newborn screening by mass spectrometry analysis has significantly enhanced the early recognition of these disorders, allowing identification of many affected patients before the onset of symptoms.
- Published
- 2015
206. NMDA Receptor Composition Differs Among Anatomically Diverse Malformations of Cortical Development
- Author
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Adele Finardi, Massimo Cossu, Stefania Bassanini, Monica Di Luca, Franco Taroni, Giorgio LoRusso, Giorgio Battaglia, Fabrizio Gardoni, Claudio Caccia, Giovanni Lasio, and Laura Tassi
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Adult ,Doublecortin Domain Proteins ,Male ,Adolescent ,Blotting, Western ,Gene Expression ,Nerve Tissue Proteins ,Biology ,Receptors, N-Methyl-D-Aspartate ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Downregulation and upregulation ,medicine ,Humans ,Child ,Cerebral Cortex ,Brain Diseases ,Epilepsy ,Neuropeptides ,Glutamate receptor ,General Medicine ,Cortical dysplasia ,medicine.disease ,Immunohistochemistry ,Magnetic Resonance Imaging ,Protein Subunits ,Heterotopia (medicine) ,nervous system ,Neurology ,Dysplasia ,Excitatory postsynaptic potential ,NMDA receptor ,Female ,Neurology (clinical) ,Glutamatergic synapse ,Microtubule-Associated Proteins ,Neuroscience - Abstract
Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.
- Published
- 2006
207. Normal expression of myelin protein zero with frame-shift mutation correlates with mild phenotype
- Author
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Davide Pareyson, Andreas J. Steck, Beat Erne, Angelo Sghirlanzoni, Franco Taroni, and Nicole Schaeren-Wiemers
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Adult ,Biopsy ,Blotting, Western ,Biology ,medicine.disease_cause ,Frameshift mutation ,Myelin ,Sural Nerve ,Peripheral myelin protein 22 ,medicine ,Humans ,Frameshift Mutation ,Demyelinating Disorder ,Mutation ,Nerve biopsy ,medicine.diagnostic_test ,General Neuroscience ,Myelin protein zero ,Immunohistochemistry ,Molecular biology ,Pedigree ,Myelin basic protein ,Phenotype ,medicine.anatomical_structure ,Immunology ,biology.protein ,Female ,Neurology (clinical) ,Myelin P0 Protein ,Myelin Proteins ,Demyelinating Diseases - Abstract
Mutations in the gene encoding for myelin protein zero (MPZ) cause inherited demyelinating peripheral neuropathies of different severity. The molecular and cellular mechanisms by which the MPZ mutations cause neuropathy are incompletely understood. We investigated MPZ, myelin basic protein, and peripheral myelin protein 22 (PMP22) protein expression levels in a nerve biopsy of a Charcot-Marie-Tooth type 1B patient heterozygous for the Val 102 frame-shift mutation. We demonstrate by quantitative immunohistochemical as well as by Western blot analyses that MPZ expression levels were not reduced in myelin membranes, a finding that is in accordance with the mild phenotype of this patient. Our data show that heterozygous 'loss-of-function' of MPZ may not necessarily lead to reduced protein levels. In conclusion, we demonstrate that careful analysis of protein expression levels in peripheral nerve tissues provides important information with respect to the understanding of the molecular basis of these neuropathies.
- Published
- 2006
208. Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells
- Author
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Bo Lönnerdal, Michael Ristow, Alan R. Buckpitt, Robert Schoenfeld, Alice Wong, Hélène Puccio, Eleonora Napoli, Shan Zhan, Franco Taroni, Laurence Reutenauer, Dexter Morin, Gino A Cortopassi, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I
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Transcription, Genetic ,MESH: Sequence Homology, Amino Acid ,MESH: Coproporphyrinogen Oxidase ,Protoporphyrins ,MESH: Amino Acid Sequence ,Mitochondrion ,MESH: Mice, Knockout ,MESH: Zinc ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Iron-Binding Proteins ,MESH: Animals ,Heme ,Cells, Cultured ,Genetics (clinical) ,Oligonucleotide Array Sequence Analysis ,Mammals ,Mice, Knockout ,0303 health sciences ,biology ,Protoporphyrin IX ,Coproporphyrinogen Oxidase ,Cytochromes c ,Heart ,MESH: Cytochromes c ,General Medicine ,Ferrochelatase ,Mitochondria ,Zinc ,MESH: Heme ,MESH: Cells, Cultured ,MESH: Mutation ,MESH: Myocardium ,MESH: Protoporphyrins ,MESH: Ferrochelatase ,MESH: Mitochondria ,Molecular Sequence Data ,MESH: Mammals ,03 medical and health sciences ,Proto-Oncogene Proteins ,Genetics ,Animals ,Humans ,Amino Acid Sequence ,MESH: Iron-Binding Proteins ,MESH: Mice ,Molecular Biology ,030304 developmental biology ,MESH: Molecular Sequence Data ,MESH: Humans ,Sequence Homology, Amino Acid ,MESH: Transcription, Genetic ,Myocardium ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Molecular biology ,MESH: Proto-Oncogene Proteins ,MESH: Heart ,Heme C ,Heme A ,chemistry ,MESH: Oligonucleotide Array Sequence Analysis ,Mutation ,Frataxin ,biology.protein ,030217 neurology & neurosurgery - Abstract
International audience; Deficiency of the frataxin mRNA alters the transcriptome, triggering neuro- and cardiodegeneration in Friedreich's ataxia. We microarrayed murine frataxin-deficient heart tissue, liver tissue and cardiocytes and observed a transcript down-regulation to up-regulation ratio of nearly 2:1 with a mitochondrial localization of transcriptional changes. Combining all mouse and human microarray data for frataxin-deficient cells and tissues, the most consistently decreased transcripts were mitochondrial coproporphyrinogen oxidase (CPOX) of the heme pathway and mature T-cell proliferation 1, a homolog of yeast COX23, which is thought to function as a mitochondrial metallochaperone. Quantitative RT-PCR studies confirmed the significant down-regulation of Isu1, CPOX and ferrochelatase at 10 weeks in mouse hearts. We observed that mutant cells were resistant to aminolevulinate-dependent toxicity, as expected if the heme pathway was inhibited. Consistent with this, we observed increased cellular protoporphyrin IX levels, reduced mitochondrial heme a and heme c levels and reduced activity of cytochrome oxidase, suggesting a defect between protoporphyrin IX and heme a. Fe-chelatase activities were similar in mutants and controls, whereas Zn-chelatase activities were slightly elevated in mutants, supporting the idea of an altered metal-specificity of ferrochelatase. These results suggest that frataxin deficiency causes defects late in the heme pathway. As ataxic symptoms occur in other diseases of heme deficiency, the heme defect we observe in frataxin-deficient cells could be primary to the pathophysiological process.
- Published
- 2005
209. Electroencephalographic Recordings of Focal Seizures in Patients Affected by Periventricular Nodular Heterotopia: Role of the Heterotopic Nodules in the Genesis of Epileptic Discharges
- Author
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Franco Taroni, Alessio Giavazzi, Tiziana Granata, Luisa Chiapparini, Giorgio Battaglia, Silvana Franceschetti, Stefania Bassanini, Adele Finardi, and Elena Freri
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Choristoma ,Electroencephalography ,Cerebral Ventricles ,Eeg patterns ,03 medical and health sciences ,Epileptic discharge ,Epilepsy ,0302 clinical medicine ,030225 pediatrics ,medicine ,Humans ,In patient ,Prospective Studies ,Cerebral Cortex ,medicine.diagnostic_test ,Periventricular Nodular Heterotopia ,Ictal eeg ,Middle Aged ,medicine.disease ,nervous system diseases ,nervous system ,Pediatrics, Perinatology and Child Health ,Female ,Epilepsies, Partial ,Neurology (clinical) ,Psychology ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Patients affected by periventricular nodular heterotopia are frequently characterized by focal drug-resistant epilepsy. To investigate the role of periventricular nodules in the genesis of seizures, we analyzed the electroencephalographic (EEG) features of focal seizures recorded by means of video-EEG in 10 patients affected by different types of periventricular nodular heterotopia and followed for prolonged periods of time at the epilepsy center of our institute. The ictal EEG recordings with surface electrodes revealed common features in all patients: all seizures originated from the brain regions where the periventricular nodular heterotopia were located; EEG patterns recorded on the leads exploring the periventricular nodular heterotopia were very similar both at the onset and immediately after the seizure's end in all patients. Our data suggest that seizures are generated by abnormal anatomic circuitries, including the heterotopic nodules and adjacent cortical areas. The major role of heterotopic neurons in the genesis and propagation of epileptic discharges must be taken into account when planning surgery for epilepsy in patients with periventricular nodular heterotopia. ( J Child Neurol 2005;20:369—377).
- Published
- 2005
210. Inadequacies of posterior probabilities for the assessment of scientific evidence
- Author
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Alex Biedermann and Franco Taroni
- Subjects
Standardization ,Management science ,Computer science ,business.industry ,Posterior probability ,Bayesian network ,Sample (statistics) ,Proposition ,Context (language use) ,Scientific evidence ,Philosophy ,Handwriting ,Artificial intelligence ,Statistics, Probability and Uncertainty ,business ,Law - Abstract
In a recent publication, Koller et al. (Probability Conclusions in Expert Opinions on Handwriting. Substantiation and Standardization of Probability Statements in Expert Opinions. Munchen: Luchterhand, 2004) elaborate recommendations as to how forensic scientists should evaluate their findings in the specific field of comparative handwriting examination. The proposed procedure is intended to standardise the calculation of posterior probabilities of propositions which are of interest to members of the court, e.g. the proposition of a certain individual being the author of a questioned handwritten sample. Koller et al. (2004) also claim that such an approach may analogously be applied in other forensic disciplines. The present paper discusses some of the compromising effects that these recommendations may have on a coherent evaluation of scientific evidence. Drawbacks of posterior probabilities for describing the probative force of evidence are contrasted with insights offered by other evaluative frameworks. Inadequate implications of posterior probabilities are illustrated and discussed in the context of examples that focus on selected aspects of combining evidence. Graphical probability models, i.e. Bayesian networks, are used with the aim of clarifying the rationale underlying the arguments presented.
- Published
- 2005
211. The evaluation of evidence in the forensic investigation of fire incidents (Part I): an approach using Bayesian networks
- Author
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Alex Biedermann, C. Semadeni, Anthony C. Davison, Olivier Delémont, and Franco Taroni
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Flammable liquid ,chemistry.chemical_compound ,Surgical approach ,chemistry ,Computer science ,Key (cryptography) ,Bayesian network ,Graphical model ,Element (criminal law) ,Law ,Data science ,Pathology and Forensic Medicine ,Variety (cybernetics) - Abstract
The forensic investigation of the origin and cause of a fire incident is a particularly demanding area of expertise. As the available evidence is often incomplete or vague, uncertainty is a key element. The present study is an attempt to approach this through the use of Bayesian networks, which have been found useful in assisting human reasoning in a variety of disciplines in which uncertainty plays a central role. The present paper describes the construction of a Bayesian network (BN) and its use for drawing inferences about propositions of interest, based upon a single, possibly non replicable item of evidence: detected residual quantities of a flammable liquid in fire debris.
- Published
- 2005
212. Decision Analysis in Forensic Science
- Author
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Franco Taroni, Silvia Bozza, and Colin Aitken
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Operations research ,forensic science ,Decision Making ,kinship determination ,Decision Support Techniques ,Pathology and Forensic Medicine ,Scientific evidence ,Business decision mapping ,Genetics ,Humans ,interpretation ,Probability ,decision analysis ,Likelihood Functions ,evaluation ,Models, Statistical ,Decision engineering ,Management science ,Forensic Sciences ,Evidential reasoning approach ,Bayes theorem ,scientific evidence ,utility ,Bayes Theorem ,Test (assessment) ,Identification (information) ,Psychology ,Decision-making models ,Decision analysis - Abstract
Forensic scientists are routinely faced with the problems of making decisions under circumstances of uncertainty (i.e., to perform or not perform a test). A decision making model in forensic science is proposed, illustrated with an example from the field of forensic genetics. The approach incorporates available evidence and associated uncertainties with the assessment of utilities (or desirability of the consequences). The paper examines a general example for which identification will be made of the decision maker, the possible actions, the uncertain states of nature, the possible source of evidence and the kind of utility assessments required. It is argued that a formal approach can help to clarify the decision process and give a coherent means of combining elements to reach a decision.
- Published
- 2005
213. A simple logical approach to questioned envelopes examination
- Author
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Franco Taroni and Williams Mazzella
- Subjects
Information retrieval ,business.industry ,Logical approach ,Artificial intelligence ,Suspect ,business ,Pathology and Forensic Medicine ,Simple (philosophy) ,Envelope (motion) ,Mathematics - Abstract
This case report outlines research undertaken as the result of a document examination case in which two envelopes were involved. The combination of the circumstances of the case and the results of the examination allows a simple application of a logical approach to pre-assess the probability that an envelope (or a package) potentially recovered at a suspect's home comes from the same batch (same source) as questioned envelopes. This highlights that it is useful to examine envelopes.
- Published
- 2005
214. Topical Review: Schizencephaly: Clinical Spectrum, Epilepsy, and Pathogenesis
- Author
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Elena Freri, Tiziana Granata, Giorgio Battaglia, Franco Taroni, Veronica Setola, and Claudio Caccia
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Pathology ,medicine.diagnostic_test ,030105 genetics & heredity ,medicine.disease ,Pathogenesis ,03 medical and health sciences ,Epilepsy ,Schizencephaly ,Cerebral malformations ,Pediatrics, Perinatology and Child Health ,medicine ,Neurology (clinical) ,Presentation (obstetrics) ,Psychology ,Functional magnetic resonance imaging - Abstract
After almost 60 years since the original description, we have reviewed the results of the more recent studies on schizencephaly in an attempt to delineate its imaging and clinical spectra of presentation and to point out the still unsettled controversies on its pathogenesis. The clinical picture is mainly based on the presence of motor deficits and mental retardation, but the severity of the clinical picture is extremely variable, mainly related to the size and location of the clefts and to the presence of associated cerebral malformations. By contrast, the outcome of epilepsy, which is present in about half of the cases and drug resistant in a third, is not strictly related to the severity of the malformation. Some clinical and functional magnetic resonance imaging studies have suggested that, beside the features of the anatomic damage, the functional reorganization of a malformed and unaffected cortex is most likely crucial in determining the clinical outcome. Review of the genetic studies and the more recent personal data suggests that the role of the EMX2 gene in schizencephaly, if any, is restricted to a minority of cases, leaving the etiopathogenesis of this brain malformation still a matter of study and debate. ( J Child Neurol 2005;20:313—318).
- Published
- 2004
215. Analysis of Dyes in Illicit Pills (Amphetamine and Derivatives)
- Author
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Franco Taroni, Till Goldmann, and Pierre Margot
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Chromatography ,European community ,Illicit Drugs ,Chemistry ,Amphetamines ,Electrophoresis, Capillary ,Bayes Theorem ,Pathology and Forensic Medicine ,Capillary electrophoresis ,Chromatography detector ,Hallucinogens ,Genetics ,Analytical strategy ,Bayesian framework ,Chromatography, Thin Layer ,Coloring Agents - Abstract
The determination of dyes present in illicit pills is shown to be useful and easy-to-get information in strategic and tactical drug intelligence. An analytical strategy including solid-phase extraction (SPE) thin-layer chromatography (TLC) and capillary zone electrophoresis equipped with a diode array detector (CZE-DAD) was developed to identify and quantify 14 hydrosoluble, acidic, synthetic food dyes allowed in the European Community. Indeed, these may be the most susceptible dyes to be found in illicit pills through their availability and easiness of use. The results show (1) that this analytical method is well adapted to small samples such as illicit pills, (2) that most dyes actually found belong to hydrosoluble, acidic, synthetic food dyes allowed in the European Community, and (3) that this evidence turns out to be important in drug intelligence and may be assessed into a Bayesian framework.
- Published
- 2004
216. A general approach to Bayesian networks for the interpretation of evidence
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Paolo Garbolino, Alex Biedermann, Colin Aitken, and Franco Taroni
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Forensic Science ,media_common.quotation_subject ,Machine learning ,computer.software_genre ,Field (computer science) ,Pathology and Forensic Medicine ,Scientific evidence ,Presentation ,Bayesian networks ,Scientific Evidence ,Humans ,Sociology ,media_common ,Structure (mathematical logic) ,Interpretation (logic) ,business.industry ,Forensic Sciences ,Bayesian network ,Bayes Theorem ,Models, Theoretical ,restrict ,Artificial intelligence ,business ,Law ,computer - Abstract
Bayesian networks (BNs) are mathematically and statistically rigorous techniques for handling uncertainty. The field of forensic science has recently attributed increased attention to the many advantages of this graphical method for assisting the evaluation of scientific evidence. However, the majority of contributions that relate to this topic restrict themselves to the presentation of already “constructed” BNs, and often, only a few explanations are given as to how one obtains a specific BN structure for a given problem. Based on several examples, the present paper will therefore attempt to explain in more detail some guiding considerations that might be helpful for the elicitation of appropriate structures for BNs.
- Published
- 2004
217. Tunisian population data on 10 Y-chromosomal loci
- Author
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Patrice Mangin, Franco Taroni, N. Dimo-Simonin, M. Ben Dhiab, Vincent Castella, M. Zemni, and C. Brandt-Casadevall
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Male ,Genetics ,education.field_of_study ,Chromosomes, Human, Y ,Tunisia ,Haplotype ,Population ,Population genetics ,Tunisian population ,Biology ,Y chromosome ,DNA Fingerprinting ,Pathology and Forensic Medicine ,Genetics, Population ,Gene Frequency ,Haplotypes ,Str loci ,Humans ,Microsatellite ,Allele ,education ,Law - Abstract
Alleles and haplotypes frequencies for 10 Y-chromosome STR loci (DYS19, DYS385 I/II, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS438 and DYS439), included in the Y-Plex™6 and Y-Plex™5 kits were determined for a Tunisian population sample of 100 male individuals.
- Published
- 2003
218. Decreased expression of genes involved in sulfur amino acid metabolism in frataxin-deficient cells
- Author
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Franco Taroni, Eleonora Napoli, Guolin Tan, and Gino A Cortopassi
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Cell ,Apoptosis ,Oxidative phosphorylation ,Mitochondrion ,Aconitase ,Trinucleotide Repeats ,Iron-Binding Proteins ,Gene expression ,Genetics ,medicine ,Humans ,Molecular Biology ,Genetics (clinical) ,Neurons ,chemistry.chemical_classification ,biology ,General Medicine ,Fibroblasts ,Molecular biology ,Cystathionine beta synthase ,Amino acid ,Amino Acids, Sulfur ,medicine.anatomical_structure ,chemistry ,Friedreich Ataxia ,Frataxin ,biology.protein - Abstract
Inherited deficiency of the mitochondrial protein frataxin causes neural and cardiac cell degeneration, and Friedreich's ataxia. Five hypotheses for frataxin's mitochondrial function have been generated, largely from work in non-human cells: iron transporter, iron-sulfur cluster assembler, iron-storage protein, antioxidant and stimulator of oxidative phosphorylation. We analyzed gene expression in three human cell types using microarrays, and identified just 48 transcripts whose expression was significantly frataxin-dependent in at least two cell types. Significant decreases in seven transcripts occurred in the sulfur amino acid (SAA) biosynthetic pathway and the iron-sulfur cluster (ISC) biosynthetic pathway to which it is connected. By contrast, we did not observe a single frataxin-dependent transcript that fits with the other four current hypotheses. Quantitative reverse-transcriptase PCR analysis of ISC-S and rhodanese transcripts confirmed that the expression of these genes involved in ISC metabolism was lower in mutants. Amino acid analysis confirmed the defect in SAA metabolism: homocystine, cysteine, cystathionine and serine were significantly decreased in frataxin-deficient cell extracts and mitochondria. An ISC defect was further confirmed by observing decreases in succinate dehydrogenase and aconitase activities, whose activities require ISCs. The ISC-U scaffold protein was specifically decreased in frataxin-deficient cells, suggesting a role for frataxin in its expression or maintenance, and sodium sulfide partially rescued the oxidant-sensitivity of the FRDA cells. Also, multiple transcripts involved in the Fas/TNF/INF apoptosis pathway were up-regulated in frataxin-deficient cells, consistent with a multi-step mechanism of Friedreich's ataxia pathophysiology, and suggesting alternative possibilities for therapeutic intervention.
- Published
- 2003
219. A methodology for illicit heroin seizures comparison in a drug intelligence perspective using large databases
- Author
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Frédéric Anglada, Pierre Margot, Franco Taroni, Laurence Dujourdy, and Pierre Esseiva
- Subjects
Illicit heroin ,Databases, Factual ,Correlation coefficient ,Illicit Drugs ,Computer science ,Forensic Medicine ,Correlation value ,Pathology and Forensic Medicine ,Heroin ,Correlation ,Method comparison ,Statistics ,Discrete cosine transform ,False positive paradox ,Humans ,Profiling (information science) ,Crime ,Law - Abstract
To characterise links between different illicit drugs chemical profiles, various distance or correlation measurements are available. Different comparison methods have been tested and a method based on a correlation coefficient using a square cosine function was chosen to compare heroin chemical profiles. Its functioning and graphical representation are described. An assessment of the number of false positives is calculated and lead to a negligible number. Moreover, it emerges from the studies that possible variations in impurity peak areas subject to possible degradations do not influence the C correlation value nor question the already established links. This solid, reliable and simple method appears therefore suitable for heroin samples comparison, links profiling and routine use.
- Published
- 2003
220. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 76
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Alessandra Erbetta, Franco Taroni, Giuseppe Lauria, Claudia Ciano, Angelo Sghirlanzoni, Luisa Chiapparini, Scaioli, Michela Morbin, Davide Pareyson, Isabella Moroni, and M Milani
- Subjects
education.field_of_study ,medicine.medical_specialty ,Pathology ,business.industry ,General Neuroscience ,Nonsense mutation ,Asymptomatic ,Median nerve ,Internal medicine ,medicine ,Connexin 32 ,Missense mutation ,Neurology (clinical) ,Evoked potential ,medicine.symptom ,education ,Ulnar nerve ,business ,Subclinical infection - Abstract
The X-linked form of Charcot-Marie-Tooth disease (CMTX) is associated with mutations in the Connexin 32 gene (Cx32) and is the second most common CMT subtype after CMT1A, in which the 17p11.2 duplication is the underlying molecular defect. CMTX is characterized by no male-to-male transmission, intermediate motor conduction velocities (MCV), and more severe disease in males. In our series of CMT patients, we found 9 different Cx32 mutations in 11 families. Overall there were 26 patients, 13 males and 13 females, aged 11–76 yrs. Age at onset ranged considerably (1–60 yrs), but symptoms began earlier in males (mean 15.4 yrs, 77% within age 20) than in females (mean 25 yrs). All patients were autonomous, but disease severity was greater in males, while 4 female carriers were asymptomatic. Pain and tremor were frequent complaints. Two patients had Babinski sign and one had rest tremor. Nerve conduction studies were performed in 23 patients (13 males, 10 females). Upper limb motor conduction velocities (MCV) ranged between 25 and 57 m/s, and were slower in males (25–48 m/s) than in females (34–57 m/s). MCV were in the upper range of CMT1 (25–38 m/s) in 10/13 males but only in 3/10 females. In some cases, nerve conduction slowing was non-uniform within single nerves, and one female patient had a previous diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy. There was considerable asymmetry of involvement between different nerves. The median nerve was often more severely affected than the ulnar nerve, and not only in females, as previously reported, but also in males. Therefore, it appears unlikely that this asymmetry is accounted for by a Lyonization phenomenon. Subclinical abnormalities of central nervous system as revealed by multimodal evoked potential studies were found in 8/10 patients. Expression of Cx32 in the brain is the likely explanation of this finding that confirms previous non-systematic observations. We found seven missense and two nonsense mutations (one novel mutation). Two families presented distinct mutations at the same codon (Arg164), while the Arg22Stop and Arg220Stop mutations were each found in two unrelated cases. Partially supported by a grant from the Italian Ministry of Health to F.T and D.P. (Progetto Ricerca Finalizzata ICS 030.3/RF00.174).
- Published
- 2003
221. Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 86
- Author
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Davide Pareyson, M Milani, Franco Taroni, M. Cesani, C Caccia, and Silvia Baratta
- Subjects
Genetics ,Mutation ,General Neuroscience ,Single-strand conformation polymorphism ,Biology ,medicine.disease_cause ,Molecular biology ,Exon ,chemistry.chemical_compound ,chemistry ,Polymorphism (computer science) ,Gene duplication ,medicine ,Neurology (clinical) ,Gene ,DNA ,Heteroduplex - Abstract
At least 15 genetic loci and ten genes have been associated with the demyelinating form of Charcot-Marie-Tooth hereditary neuropathy and related disorders. As pathogenic mutations have been identified in more and more genes, the labor and expense of screening for such mutations has increased substantially. Using conventional methods such as direct sequencing, single-strand conformation polymorphism (SSCP), or heteroduplex analysis, molecular diagnosis of CMT remains laborious due to the large number of exons to be screened. Some genes (MPZ, PMP22, EGR2, GJB1) are small and have to be analyzed in a relatively large number of patients while other rarer genes, such as periaxin (PRX, 19q13), are too large (7 exons encoding transcripts of 4.8–5.5 kilobases) to be easily included in a molecular diagnostic panel. Furthermore, the sensitivity of the more economical techniques (SSCP and heteroduplex analysis) is far from being optimal ( ). Denaturing High-Performance Liquid Chromatography (DHPLC) is a newly developed method to scan DNA for mutations, which is capable of automated high-throughput analysis that does not require modified PCR primers, specific reagent arrays or detection labels, or any sample pretreatment other than PCR. We have undertaken the mutational analysis of some genes associated with CMT1 and related neuropathies by using DHPLC. Optimal conditions have been determined for DHPLC analysis of MPZ, PMP22, GJB1 and PRX genes in an initial group of 30 patients with severe demyelinating neuropathy, negative for the common 17p11 duplication. The very high sensitivity of the method was demonstrated by analyzing a control group of patients with known mutations in the MPZ, PMP22 and GJB1 genes. The work is still in progress. Thus far, DHPLC has resolved all the mutations previously detected by sequencing and allowed the identification of a number of polymorphic variants in the PRX gene and a novel disease mutation in MPZ gene exon 4 in a patient with an intermediate (axonal-demyelinating) form of CMT. Interestingly, this mutation had consistently appeared as homozygous at previous direct sequencing analysis. DHPLC clearly showed the heterozygous state of the mutation, thus demonstrating the power of this technique also in identifying sequencing artifact or mutation mosaicism, if any. Partially supported by a grant Ricerca Finalizzata Ministero della Sanita to FT.
- Published
- 2003
222. Different consequences of EGR2 mutants on the transactivation of human cx32 promoter
- Author
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Emilia Bellone, Marco Musso, P Balestra, Franco Taroni, and Paola Mandich
- Subjects
Transcriptional Activation ,Recombinant Fusion Proteins ,Mutant ,DNA Footprinting ,Biology ,Connexins ,lcsh:RC321-571 ,Myelin ,Transactivation ,Charcot-Marie-Tooth Disease ,Genes, Regulator ,Transcriptional regulation ,medicine ,Humans ,Protein Isoforms ,Peripheral Nerves ,Promoter Regions, Genetic ,education ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Gene ,Transcription factor ,Early Growth Response Protein 2 ,Myelin Sheath ,education.field_of_study ,Binding Sites ,Base Sequence ,Zinc Fingers ,Promoter ,DNA ,Molecular biology ,DNA-Binding Proteins ,Phenotype ,medicine.anatomical_structure ,Neurology ,Mutation ,Connexin 32 ,Demyelinating Diseases ,HeLa Cells ,Transcription Factors - Abstract
The early growth response 2 (EGR2) transcription factor plays a crucial role in peripheral nerve myelination. Mutations of this gene are associated with a wide variety of demyelinating neuropathies differing from each other in the severity of nerve injury. Although the expression of EGR2 mutants inhibits the transactivation of myelin gene promoters, the exact molecular mechanism by which these mutations cause the alteration of the myelination process is still unknown. Recently, it was reported that EGR2 is directly involved in the transcriptional regulation of Connexin 32, a myelin gene frequently mutated in peripheral neuropathies. Here we describe the differential effect of two EGR2 mutants; while mutant D355V partially induces Cx32 promoter, mutant R381H does not. Furthermore, we show that a sequence located at -216, recognized by the wild-type and the mutant D355V recombinant proteins, is relevant for promoter transactivation.
- Published
- 2003
223. Tunisian population allele frequencies for 15 PCR-based loci
- Author
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Franco Taroni, Patrice Mangin, M. Zemni, M. Ben Dhiab, C Gehrig, C. Brandt-Casadevall, and N. Dimo-Simonin
- Subjects
Genetics ,education.field_of_study ,Arabic ,Population ,Tunisian population ,Population genetics ,General Medicine ,Biology ,language.human_language ,Genotype frequency ,Genotype ,language ,education ,Allele frequency - Abstract
Genotype and allele frequencies distribution for 15 PCR-based loci (D3S1358, THO1, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, VWA, D8S1179, TPOX and FGA) were determined for a Tunisian population sample. The examined population consists of a mixture of Arabic and Berber individuals coming from the three different regions of the country: North, Centre and South.
- Published
- 2003
224. Evaluation of links in heroin seizures
- Author
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O. Gueniat, Franco Taroni, Pierre Margot, Laurence Dujourdy, Giulia Barbati, Pierre Esseiva, Frédéric Anglada, L., Dujourdy, Barbati, Giulia, F., Taroni, O., Guéniat, P., Esseiva, F., Anglada, and P., Margot
- Subjects
adverse effects, Humans, Likelihood Functions, Model ,Narcotics ,Computer science ,Statistics as Topic ,Drug profiling ,Measure (mathematics) ,methods ,Pathology and Forensic Medicine ,Heroin ,adverse effects, Reproducibility of Results, Seizure ,chemically induced, Statistics as Topic ,Bayes' theorem ,Models ,Seizures ,Statistics ,Statistical, Narcotic ,medicine ,Discrete cosine transform ,Humans ,statistics /&/ numerical data, Heroin ,Likelihood Functions ,Models, Statistical ,business.industry ,Forensic Medicine ,adverse effects, Humans, Likelihood Functions, Models ,Statistical, Narcotics ,adverse effects, Reproducibility of Results, Seizures ,Reproducibility of Results ,Pattern recognition ,Statistical ,statistics /&/ numerical data ,adverse effects ,chemically induced ,Artificial intelligence ,business ,Law ,Simulation methods ,medicine.drug - Abstract
The evaluation of a link between two heroin seizures using a descriptive method is presented. It is based on the measure of the angles between two chromatograms assimilated to vectors, and interpreted using a continuous approach based on the likelihood ratio of Bayes' theorem. A complete evaluation model thus avoids the drawbacks of decision thresholds used until now to establish a link. Validation is obtained through tests and simulation methods.
- Published
- 2003
225. Evaluation of a simplified method of the conduction system analysis in 110 forensic cases
- Author
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Franco Taroni, Beat Horisberger, Katarzyna Michaud, Nathalie Romain, and Patrice Mangin
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Autopsy ,Sudden death ,Pathology and Forensic Medicine ,Death, Sudden ,Heart Conduction System ,medicine ,Humans ,Child ,Pathological ,Cause of death ,business.industry ,Medical jurisprudence ,Infant ,Forensic Medicine ,Middle Aged ,Sudden infant death syndrome ,Fibrosis ,Atrioventricular node ,Surgery ,medicine.anatomical_structure ,Adipose Tissue ,Female ,Radiology ,Electrical conduction system of the heart ,business ,Law ,Sudden Infant Death - Abstract
A simplified method of the His bundle analysis is evaluated by the study of 110 forensic cases. The atrioventricular node or its part were observed in 96 cases (87.3%), penetrating bundle in 92 cases (83.6%), branching and left bundles branch in 109 cases (99.1%) and right bundle branch in 73 cases (66.4%). The changes such as fibrosis and fatty infiltration show statistically significant differences (P
- Published
- 2002
226. Evaluation of scientific evidence using Bayesian networks
- Author
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Franco Taroni and Paolo Garbolino
- Subjects
Adult ,Male ,Likelihood Functions ,business.industry ,Probabilistic logic ,Bayesian network ,Inference ,Bayes Theorem ,Forensic Medicine ,Logic model ,Pathology and Forensic Medicine ,Scientific evidence ,Bayesian statistics ,Bayes' theorem ,Humans ,Female ,Sociology ,Artificial intelligence ,business ,Law ,Simple (philosophy) - Abstract
Bayesian networks provide a valuable aid for representing epistemic relationships in a body of uncertain evidence. The paper proposes some simple Bayesian networks for standard analysis of patterns of inference concerning scientific evidence, with a discussion of the rationale behind the nets, the corresponding probabilistic formulas, and the required probability assessments.
- Published
- 2002
227. Evaluation and presentation of forensic DNA evidence in European laboratories
- Author
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D.J. Werrett, J.A. Lambert, L. Fereday, and Franco Taroni
- Subjects
Likelihood Functions ,Dna evidence ,media_common.quotation_subject ,Bayes Theorem ,DNA ,Forensic Medicine ,Pathology and Forensic Medicine ,Europe ,Forensic dna ,Presentation ,Humans ,Ethnology ,Sociology ,Humanities ,media_common - Abstract
La premiere partie de cet article decrit le theoreme de Bayes et son application pratique aux indices scientifiques. Deuxiemement, les conclusions proposees par les laboratoires ADN europeens sont presentees, analysees et commentees. Finalement, les auteurs repetent leur proposition d'adopter un systeme de rapport de vraissemblance justifie par l'utilite de l'approche dans le contexte pratique des cas d'ADN. Il faut noter que cette approche souligne les questions principales que les experts doivent repondre au tribunal : avec quel degre l'indice soutient-il l'hypothese de l'accusation? Et avec quel degre l'indice soutient-il l'hypothese de la defense?.
- Published
- 2002
228. Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia
- Author
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Franco Taroni, Elisabetta Rovelli, Alessandro Campanella, Paolo Santambrogio, Sonia Levi, Anna Cozzi, Alessandro, Campanella, Elisabetta, Rovelli, Paolo, Santambrogio, Anna, Cozzi, Franco, Taroni, and Levi, SONIA MARIA ROSA
- Subjects
Iron ,Gene Expression ,Antimycin A ,Mitochondrion ,medicine.disease_cause ,Mitochondrial Proteins ,chemistry.chemical_compound ,Mice ,Genetics ,medicine ,Animals ,Humans ,Viability assay ,Molecular Biology ,Genetics (clinical) ,Cells, Cultured ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,MITOCHONDRIAL FERRITIN ,General Medicine ,Articles ,Fibroblasts ,Molecular biology ,Mitochondria ,Cytosol ,Oxidative Stress ,chemistry ,Gene Expression Regulation ,Friedreich Ataxia ,Ferritins ,Frataxin ,biology.protein ,Reactive Oxygen Species ,Oxidation-Reduction ,Oxidative stress ,HeLa Cells - Abstract
Mitochondrial ferritin (FtMt) is a nuclear-encoded iron-sequestering protein that specifically localizes in mitochondria. In mice it is highly expressed in cells characterized by high-energy consumption, while is undetectable in iron storage tissues like liver and spleen. FtMt expression in mammalian cells was shown to cause a shift of iron from cytosol to mitochondria, and in yeast it rescued the defects associated with frataxin deficiency. To study the role of FtMt in oxidative damage, we analyzed the effect of its expression in HeLa cells after incubation with H(2)O(2) and Antimycin A, and after a long-term growth in glucose-free media that enhances mitochondrial respiratory activity. FtMt reduced the level of reactive oxygen species (ROS), increased the level of adenosine 5'triphosphate and the activity of mitochondrial Fe-S enzymes, and had a positive effect on cell viability. Furthermore, FtMt expression reduces the size of cytosolic and mitochondrial labile iron pools. In cells grown in glucose-free media, FtMt level was reduced owing to faster degradation rate, however it still protected the activity of mitochondrial Fe-S enzymes without affecting the cytosolic iron status. In addition, FtMt expression in fibroblasts from Friedreich ataxia (FRDA) patients prevented the formation of ROS and partially rescued the impaired activity of mitochondrial Fe-S enzymes, caused by frataxin deficiency. These results indicate that the primary function of FtMt involves the control of ROS formation through the regulation of mitochondrial iron availability. They are consistent with the expression pattern of FtMt observed in mouse tissues, suggesting a FtMt protective role in cells characterized by defective iron homeostasis and respiration, such as in FRDA.
- Published
- 2009
229. Co-occurrence of amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease type 2A in a patient with a novel mutation in the mitofusin-2 gene
- Author
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Davide Pareyson, Franco Taroni, Chiara Marchesi, Gian Maria Fabrizi, Claudia Ciano, Cinzia Gellera, Ettore Salsano, Antonino Uncini, M Milani, and Lorenzo Nanetti
- Subjects
Pathology ,medicine.medical_specialty ,Weakness ,Hearing loss ,Comorbidity ,Audiology ,Charcot-Marie-Tooth neuropathy ,Amyotrophic Lateral Sclerosis ,CMT2A ,Mitofusin-2 ,Motor neuron disease ,GTP Phosphohydrolases ,Mitochondrial Proteins ,Fasciculation ,Dysarthria ,Atrophy ,Charcot-Marie-Tooth Disease ,medicine ,Humans ,Amyotrophic lateral sclerosis ,Genetics (clinical) ,business.industry ,Membrane Proteins ,Middle Aged ,Motor neuron ,medicine.disease ,Dysphagia ,medicine.anatomical_structure ,Neurology ,Mutation ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Female ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Mitofusin-2 gene (MFN2) mutations cause Charcot-Marie-Tooth type 2A (CMT2A), sometimes complicated by additional features such as optic atrophy, hearing loss, upper motor neuron signs and cerebral white-matter abnormalities. Here we report, for the first time, the occurrence of motor neuron disease, consistent with amyotrophic lateral sclerosis (ALS), in a 62-year-old woman affected by early-onset slowly progressive CMT2A, due to a novel MFN2 mutation. After age 60, rate of disease progression changed and she rapidly developed generalised muscle wasting, weakness, and fasciculations, together with dysarthria and dysphagia. Clinical features, EMG findings, and fast progression were consistent with ALS superimposed on CMT.
- Published
- 2011
230. Subclinical leukodystrophy and infertility in a man with a novel homozygous CLCN2 mutation
- Author
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Nereo Bresolin, Davide Pareyson, Claudia Ciano, Serena Caldarazzo, Anna Sagnelli, Simone Nava, Daniela Di Bella, Sara Bonato, Ettore Salsano, Gioacchino Tedeschi, Franco Taroni, Mario Savoiardo, Laura Farina, DI BELLA, D, Pareyson, D, Savoiardo, M, Farina, L, Ciano, C, Caldarazzo, S, Sagnelli, A, Bonato, S, Nava, S, Bresolin, N, Tedeschi, Gioacchino, Taroni, F, and Salsano, E.
- Subjects
Infertility ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,medicine.disease_cause ,Leukoencephalopathy ,Chloride Channels ,Medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Infertility, Male ,Subclinical infection ,Neuroradiology ,Genetic testing ,CLCN2 ,Genetics ,Mutation ,biology ,medicine.diagnostic_test ,business.industry ,Leukodystrophy ,Homozygote ,Leukodystrophy, Metachromatic ,medicine.disease ,CLC-2 Chloride Channels ,biology.protein ,Neurology (clinical) ,business - Abstract
Mutations in the CLCN2 gene encoding ClC-2, a chloride channel implicated in brain ion and water homeostasis, have been recently associated with a rare autosomal recessive leukoencephalopathy, characterized by specific MRI findings caused by chronic white matter edema.1 Acknowledgment: The authors thank Mario Savoiardo, an Italian pioneer in neuroradiology, who died during the revision process of this article, for his help, insightful comments, and diagnoses. The authors and his friends around the world will miss him.
- Published
- 2014
231. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2
- Author
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Ellen, Cottenie, Andrzej, Kochanski, Albena, Jordanova, Boglarka, Bansagi, Magdalena, Zimon, Alejandro, Horga, Zane, Jaunmuktane, Paola, Saveri, Vedrana Milic, Rasic, Jonathan, Baets, Marina, Bartsakoulia, Rafal, Ploski, Pawel, Teterycz, Milos, Nikolic, Ros, Quinlivan, Matilde, Laura, Mary G, Sweeney, Franco, Taroni, Michael P, Lunn, Isabella, Moroni, Michael, Gonzalez, Michael G, Hanna, Conceicao, Bettencourt, Elodie, Chabrol, Andre, Franke, Katja, von Au, Markus, Schilhabel, Dagmara, Kabzińska, Irena, Hausmanowa-Petrusewicz, Sebastian, Brandner, Siew Choo, Lim, Haiwei, Song, Byung-Ok, Choi, Rita, Horvath, Ki-Wha, Chung, Stephan, Zuchner, Davide, Pareyson, Matthew, Harms, Mary M, Reilly, and Henry, Houlden
- Subjects
Adult ,Models, Molecular ,Base Sequence ,Molecular Sequence Data ,Mutation, Missense ,Chromosome Mapping ,Sequence Analysis, DNA ,Pedigree ,Phenotype ,Haplotypes ,Sural Nerve ,Charcot-Marie-Tooth Disease ,Report ,Protein Interaction Mapping ,Humans ,Exome ,Female - Abstract
Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5′ region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels.
- Published
- 2014
232. Evaluation of DNA profiling results
- Author
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Paolo Garbolino, Silvia Bozza, Franco Taroni, Colin Aitken, and Alex Biedermann
- Subjects
DNA profiling ,Computer science ,Bayesian network ,Computational biology ,Bioinformatics - Published
- 2014
233. Bayesian decision networks
- Author
-
Silvia Bozza, Franco Taroni, Alex Biedermann, Colin Aitken, and Paolo Garbolino
- Subjects
Computer science ,business.industry ,Bayesian probability ,Artificial intelligence ,business ,Machine learning ,computer.software_genre ,Decision networks ,computer - Published
- 2014
234. The logic of Bayesian networks and influence diagrams
- Author
-
Colin Aitken, Alex Biedermann, Silvia Bozza, Paolo Garbolino, and Franco Taroni
- Subjects
Discrete mathematics ,Theoretical computer science ,Black box ,Bayesian network ,Influence diagram ,Graphical model ,Mathematics - Published
- 2014
235. Evaluation of scientific findings in forensic science
- Author
-
Franco Taroni, Silvia Bozza, Colin Aitken, Alex Biedermann, and Paolo Garbolino
- Subjects
Forensic science ,Bayes' theorem ,Computer science ,Data science - Published
- 2014
236. Aspects of combining evidence
- Author
-
Franco Taroni, Colin Aitken, Silvia Bozza, Alex Biedermann, and Paolo Garbolino
- Subjects
Computer science ,Bayesian network ,Criminology ,Data science - Published
- 2014
237. Qualitative, sensitivity and conflict analyses
- Author
-
Franco Taroni, Alex Biedermann, Paolo Garbolino, Silvia Bozza, and Colin Aitken
- Subjects
Probability theory ,Statistics ,Econometrics ,Bayesian network ,Sensitivity (control systems) ,Sensitivity analyses ,Mathematics - Published
- 2014
238. Evaluation given activity level propositions
- Author
-
Franco Taroni, Alex Biedermann, Paolo Garbolino, Colin Aitken, and Silvia Bozza
- Subjects
Activity level ,Engineering ,business.industry ,Bayesian network ,Artificial intelligence ,business - Published
- 2014
239. Networks for continuous models
- Author
-
Alex Biedermann, Silvia Bozza, Colin Aitken, Franco Taroni, and Paolo Garbolino
- Subjects
Computer science ,business.industry ,Distributed computing ,Pattern recognition ,Artificial intelligence ,business - Published
- 2014
240. Object-oriented networks
- Author
-
Silvia Bozza, Colin Aitken, Alex Biedermann, Franco Taroni, and Paolo Garbolino
- Subjects
Object-oriented programming ,business.industry ,Computer science ,Bayesian network ,Artificial intelligence ,business ,Genealogy - Published
- 2014
241. Evaluation given crime level propositions
- Author
-
Alex Biedermann, Colin Aitken, Franco Taroni, Silvia Bozza, and Paolo Garbolino
- Subjects
Bayesian network ,Criminology ,Psychology - Published
- 2014
242. The logic of decision
- Author
-
Silvia Bozza, Alex Biedermann, Franco Taroni, Colin Aitken, and Paolo Garbolino
- Subjects
Proof calculus ,Bayesian probability ,Calculus ,Paraconsistent logic ,Non-classical logic ,Algorithm ,Cox's theorem ,Mathematics ,Logical calculus - Published
- 2014
243. Evaluation given source level propositions
- Author
-
Franco Taroni, Silvia Bozza, Colin Aitken, Alex Biedermann, and Paolo Garbolino
- Subjects
Computer science ,Bayesian network ,Data mining ,Source level ,computer.software_genre ,computer - Published
- 2014
244. Frontal cortex BOLD signal changes in premanifest Huntington disease: a possible fMRI biomarker
- Author
-
S. Piacentini, Stefano Di Donato, Maria Luisa Mandelli, Marina Grisoli, Nicola Bertolino, Lorenzo Nanetti, Mario Savoiardo, Anna Nigri, Franco Taroni, F. Ghielmetti, Caterina Mariotti, Stefania Ferraro, Francesca Epifani, and Maria Grazia Bruzzone
- Subjects
Adult ,Male ,genetic structures ,Prefrontal Cortex ,behavioral disciplines and activities ,Article ,Inhibition of return ,Correlation ,Young Adult ,Cortex (anatomy) ,medicine ,Image Processing, Computer-Assisted ,Humans ,Prefrontal cortex ,medicine.diagnostic_test ,Magnetic resonance imaging ,Frontal eye fields ,Magnetic Resonance Imaging ,Functional imaging ,Oxygen ,medicine.anatomical_structure ,Huntington Disease ,Biomarker (medicine) ,Female ,Neurology (clinical) ,Psychology ,Neuroscience - Abstract
Objective: To identify a possible functional imaging biomarker sensitive to the earliest neural changes in premanifest Huntington disease (preHD), allowing early therapeutic approaches aimed at preventing or delaying clinical onset. Methods: Sixteen preHD and 18 healthy participants were submitted to anatomical acquisitions and functional MRI (fMRI) acquisitions during the execution of the exogenous covert orienting of attention task. Due to strong a priori hypothesis, all fMRI correlation analyses were restricted to the following: (1) the frontal oculomotor cortex identified by the means of a prosaccadic task, comprising frontal eye fields and supplementary frontal eye fields; and (2) the data collected during inhibition of return, a phenomenon occurring during the executed task. In preHD, multiple regression analysis was performed between fMRI data and the probability to develop the disease in the next 5 years (p5HD). Moreover, mean blood oxygen level–dependent (BOLD) signal changes in the frontal oculomotor cortex and striatal volumes were linearly correlated with p5HD. Results: In preHD, multiple regression analysis showed that clusters of activity strongly correlated with p5HD in the right frontal oculomotor cortex. Importantly, mean BOLD signal changes of this region correlated with p5HD ( r 2 = 0.52). Among the considered striatal volumes, a modest correlation ( r 2 = 0.29) was observed in the right putamen and p5HD. Conclusion: fMRI activations in the right-frontal oculomotor cortex during inhibition of return can be considered a possible functional imaging biomarker in preHD.
- Published
- 2014
245. Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial
- Author
-
Massimo, Pandolfo, Javier, Arpa, Martin B, Delatycki, Kim Hanh, Le Quan Sang, Caterina, Mariotti, Arnold, Munnich, Irene, Sanz-Gallego, Geneieve, Tai, Mark A, Tarnopolsky, Franco, Taroni, Michael, Spino, and Fernando, Tricta
- Subjects
Adult ,Male ,Adolescent ,Dose-Response Relationship, Drug ,Pyridones ,Iron Chelating Agents ,Severity of Illness Index ,Ventricular Function, Left ,Disability Evaluation ,Electrocardiography ,Young Adult ,Treatment Outcome ,Double-Blind Method ,Friedreich Ataxia ,Humans ,Deferiprone ,Female ,Child - Abstract
We conducted a 6-month, randomized, double-blind, placebo-controlled study to assess safety, tolerability, and efficacy of deferiprone in Friedreich ataxia (FRDA).Seventy-two patients were treated with deferiprone 20, 40, or 60mg/kg/day or placebo, divided into 2 daily doses. Safety was the primary objective; secondary objectives included standardized neurological assessments (Friedreich Ataxia Rating Scale [FARS], International Cooperative Ataxia Rating Scale [ICARS], 9-Hole Peg Test [9HPT], Timed 25-Foot Walk, Low-Contrast Letter Acuity), general functional status (Activities of Daily Living), and cardiac assessments.Deferiprone was well tolerated at 20mg/kg/day, whereas more adverse events occurred in the 40mg/kg/day than in the placebo group. The 60mg/kg/day dose was discontinued due to worsening of ataxia in 2 patients. One patient on deferiprone 20mg/kg/day experienced reversible neutropenia, but none developed agranulocytosis. Deferiprone-treated patients receiving 20 or 40mg/kg/day showed a decline in the left ventricular mass index, compared to an increase in the placebo-treated patients. Patients receiving 20mg/kg/day of deferiprone had no significant change in FARS, similar to the placebo-treated patients, whereas those receiving 40mg/kg/day had worsening in FARS and ICARS scores. The lack of deterioration in the placebo arm impaired the ability to detect any potential protective effect of deferiprone. However, subgroup analyses in patients with less severe disease suggested a benefit of deferiprone 20mg/kg/day on ICARS, FARS, kinetic function, and 9HPT.This study demonstrated an acceptable safety profile of deferiprone at 20mg/kg/day for the treatment of patients with FRDA. Subgroup analyses raise the possibility that, in patients with less severe disease, deferiprone 20mg/kg/day may reduce disease progression, whereas higher doses appear to worsen ataxia.
- Published
- 2014
246. DNA, statistics and the law: a cross-disciplinary approach to forensic inference
- Author
-
Franco Taroni, Alex Biedermann, and Joëlle Vuille
- Subjects
DNA transfer ,lcsh:QH426-470 ,Computer science ,forensicDNA profiling,interpretation,probability theory,commercialization,DNA transfer,low-template DNA analysis,forensic molecular biology,bacterial DNA ,Face (sociological concept) ,Context (language use) ,low-template DNA analysis ,Commercialization ,Critical mass (sociodynamics) ,03 medical and health sciences ,0302 clinical medicine ,probability theory ,Statistics ,Genetics ,forensic molecular biology ,030216 legal & forensic medicine ,Meaning (existential) ,Genetics (clinical) ,interpretation ,commercialization ,030304 developmental biology ,0303 health sciences ,forensic DNA profiling ,Interpretation (philosophy) ,Editorial Article ,16. Peace & justice ,bacterial DNA ,lcsh:Genetics ,Scholarship ,Legal process (jurisprudence) ,Law ,Molecular Medicine - Abstract
The use of results of DNA analyses in the legal process is a highly ambivalent topic. On the one hand, scientists have never been in a better position to analyse biological matter of various natures, even in limited quantities and degraded conditions. On the other hand, the increasing amounts of scientific data that can be generated through modern analytical processes do not necessarily imply that evaluative questions that arise in the legal context are given more satisfactory answers. A fundamental question that has accompanied DNA analyses since the early days of their use in the legal process thus remains: how do we handle the challenges presented to us by the use of contemporary scientific and technological developments in the field of law? Under the general theme “DNA, statistics and the law,” the collection of articles in this Frontiers Research Topic pursues the goal of investigating this question from an interdisciplinary perspective, and with an emphasis on both current and future challenges. As pointed out by Gunn et al. (2014) and Leake (2013), the forensic interest in DNA goes well beyond the standard approaches to DNA profiling that represent the current state-of-the-art in many contemporary legal systems, and this raises questions as to how new forms of data ought to be dealt with in an operational perspective (Milot et al., 2013). Although these frontiers topics clarify the extent to which there is room for exciting future research in this area, it should not distract us from the fact that even in the current state of forensic practice, there are hurdles and pressing topics that ask for efficient answers. Controversies over legal cases, such as the Perugia case (Vecchiotti and Zoppis, 2013), reveal that the field is still facing difficulties in setting the meaning of DNA profiling results appropriately into context (Champod, 2013; McKenna, 2013). One might be tempted to conclude that this is an issue that is confined to (and could thus be resolved within) the intersection between forensic science and the law. This perspective might, however, fall short of further dimensions, such as commercialization (Jackson, 2013). The publication of opinion pieces on this topic helps raise awareness on this topic and address some of this deficit. On a methodological account, the field of statistics is often invoked as a remedy to deal with evaluative questions and many discussants tend to emphasize its traditional facet concerned with data processing. The case of statistics is more general, however, because it is a branch that involves an additional characterizing feature: reasoning coherently in the face of uncertainty (known in the context as forensic inference), using probability theory. Indeed, existing literature abounds in rigorous and coherent approaches to cope with intricate evaluative questions (Biedermann, 2013; Juchli, 2013) of the kind that are also encountered in connection with forensic DNA. It is with some frustration, however, that we note that discussions surrounding evaluative questions, using probability, are still fraught with problems that have debates for a very long time. Prior probabilities are one example for this (Thompson et al., 2013). In summary, the contributions in this Research Topic convince us that the extension of technical frontiers should also be accompanied by conceptual developments and understandings. Indeed, during personal discussions with the Topic Editors, one reviewer (Sheila Willis, Eolaiocht Fhoireinseach Eireann, Forensic Science Laboratory, Ireland) raised cultural understandings as a further relevant factor: “I think the problem is much deeper. The use of matching DNA as a heuristic for a definite link between person and place is embedded in the minds of scientists as well as jurors in spite of the scholarship to the contrary. The discriminating power of DNA has had a paradoxical effect in the development of forensic science. On one hand it prompted forensic science to be valued and used in a very widespread manner but on the other hand it promoted the commodisation of forensic science with the belief that the test result is all-important and the context irrelevant. This latter view prompts the approach that the test can be produced anywhere and loses sight for the need of the very evaluation (…). It is vital that we address this. It is mixed with the commercialization issues but to focus too much on that aspect is to ignore the wider issues that also need to be addressed by: the publication of high profile cases where this approach has unfortunate consequences; increased education; critical mass of scientific opinion in favor of the approach argued for (…).” We cannot but agree and hope that the collected papers in this Research Topic will be of interest to both scientists and other participants in the legal process. We thank all contributors and distinguished reviewers for their efforts to make this original collection timely and highly useful.
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- 2014
247. X-linked Charcot-Marie-Tooth type 1: stroke-like presentation of a novel GJB1 mutation
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Anna, Sagnelli, Giuseppe, Piscosquito, Luisa, Chiapparini, Claudia, Ciano, Ettore, Salsano, Paola, Saveri, Micaela, Milani, Franco, Taroni, and Davide, Pareyson
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Adult ,Male ,Stroke ,Charcot-Marie-Tooth Disease ,Mutation ,Brain ,Humans ,Magnetic Resonance Imaging ,Connexins - Abstract
X-linked Charcot-Marie-Tooth type 1 (CMTX1) is the second most common type of CMT and is caused by mutations in the Gap-Junction Beta-1 gene (GJB1), encoding connexin 32 which is expressed in Schwann cells as well as in oligodendrocytes. More than 400 GJB1 mutations have been described to date. Many mutation-carrier males have subclinical central nervous system (CNS) involvement, a few show mild CNS clinical signs, whereas only rarely overt though transient CNS dysfunction occurs. We report a 29-year-old man with CMTX1 who, at 16 years, showed short-lived CNS symptoms with transitory white matter abnormalities on cerebral magnetic resonance imaging (MRI) as first clinical presentation of a novel GJB1 mutation (p.Gln99_His100insGln). He had three consecutive episodes of right hemiparesis, together with sensory loss in the paretic limbs and expressive aphasia, all lasting a few hours, over a 2-day period, with concurrent white matter hyperintensity on MRI. These "stroke-like" episodes occurred just after arriving at sea level, after travelling from home at 700 m of altitude. Only a few years later did symptoms of peripheral neuropathy appear. In conclusion, CMTX1 should be included in the differential diagnosis of diseases characterized by transient CNS symptoms and white matter abnormalities on MRI.
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- 2014
248. Bayesian networks for probabilistic inference and decision analysis in forensic science
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Colin Aitken, Silvia Bozza, Alex Biedermann, Franco Taroni, and Paolo Garbolino
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Bayesian decision theory ,business.industry ,Computer science ,Bayesian networks ,Forensic science ,Bayesian network ,Probabilistic inference ,Machine learning ,computer.software_genre ,Bayesian statistics ,Frequentist inference ,Fiducial inference ,Influence diagram ,Artificial intelligence ,business ,computer ,Decision analysis - Published
- 2014
249. Bayesian Networks for Probabilistic Inference and Decision Analysis in Forensic Science. 2. ed
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Franco, Taroni, Alex, Biedermann, Silvia, Bozza, Garbolino, Paolo, and Colin, Aitken
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Bayesian networks - Published
- 2014
250. Decision analysis for the genotype designation in low-template-DNA profiles
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Franco Taroni, Simone Gittelson, Silvia Bozza, and Alex Biedermann
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Bayes estimator ,Genotype ,Models, Genetic ,Bayesian decision theory ,Bayes Theorem ,Influence diagram ,Replicate ,DNA ,Decision problem ,DNA Fingerprinting ,Pathology and Forensic Medicine ,Decision Support Techniques ,Electropherogram ,Low-level-DNA threshold ,Statistics ,Genetics ,Probability distribution ,Humans ,Algorithm ,Expected loss ,Alleles ,Decision analysis ,Mathematics - Abstract
What genotype should the scientist specify for conducting a database search to try to find the source of a low-template-DNA (lt-DNA) trace? When the scientist answers this question, he or she makes a decision. Here, we approach this decision problem from a normative point of view by defining a decision-theoretic framework for answering this question for one locus. This framework combines the probability distribution describing the uncertainty over the trace's donor's possible genotypes with a loss function describing the scientist's preferences concerning false exclusions and false inclusions that may result from the database search. According to this approach, the scientist should choose the genotype designation that minimizes the expected loss. To illustrate the results produced by this approach, we apply it to two hypothetical cases: (1) the case of observing one peak for allele xi on a single electropherogram, and (2) the case of observing one peak for allele xi on one replicate, and a pair of peaks for alleles xi and xj, i ≠ j, on a second replicate. Given that the probabilities of allele drop-out are defined as functions of the observed peak heights, the threshold values marking the turning points when the scientist should switch from one designation to another are derived in terms of the observed peak heights. For each case, sensitivity analyses show the impact of the model's parameters on these threshold values. The results support the conclusion that the procedure should not focus on a single threshold value for making this decision for all alleles, all loci and in all laboratories.
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- 2014
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