Beyond traditional paternity and identification cases. Selecting the most probable pedigree

The paper extends on the traditional methodology used to quantify DNA evidence in paternity or identification cases. By extending we imply that there are more than two alternatives to choose between. In a standard paternity case the two competing explanations H(1): "John Doe is the father of the child and H(2): "A random man is the father of the child, are typically considered. A paternity index of 100000 implies that the data is 100000 more likely assuming hypothesis H(1) rather than H(2). If H(2) is replaced by "A brother of John Doe is the father", the LR may change dramatically. The main topic of this paper is to determine the most probable pedigree given a certain set of data including DNA profiles. In the previous example this corresponds to determining the most likely relation between John Doe and the child. Based on DNA obtained from victims of a fire, bodies found in an ancient grave or from individuals seeking to confirm their anticipated family relations, we would like to determine the most probable pedigree. The approach we present provides the possibility to combine non-DNA evidence, say age of individuals, and DNA profiles. The program familias, obtainable as shareware from http://www.nr.no/familias, delivers the probabilities for the various family constellations. More precisely, the information (if any) prior to DNA is combined with the DNA-profiles in a Bayesian manner to deliver the posterior probabilities. We exemplify using the well published Romanov data where the accepted solution emerges among 4536 possibilities considered. Various other applications based on forensic case work are discussed. In addition we have simulated data to resemble an incest case. Since the true family relation is known in this case, we may evaluate the method.     

An analysis of the usefulness of specific stages in the pathologic investigation of sudden infant death

Retrospective analysis of autopsy findings in 60 infants who had been found unexpectedly dead in their cribs or beds in South Australia from 1994 to 1998 was undertaken to determine the diagnostic usefulness of individual stages in the postmortem investigation. Positive findings occurred in 2 of 43 scene examinations (3%), 2 of 60 external examinations (3%), 2 of 11 radiologic examinations (18%), 8 of 60 internal examinations (13%), 7 of 60 histologic examinations (12%), and 3 of 58 microbiologic examinations (5%). No positive findings were detected on toxicologic screening. Not every case underwent each diagnostic step. This gave alternative diagnoses to sudden infant death syndrome (SIDS) in 15 cases (25%). This study demonstrates an increase in the percentage of cases of unexpected infant death due to causes other than SIDS; it also shows the diagnostic yield of individual stages in the postmortem evaluation of such cases. Negative findings were important in giving validity to the diagnosis in the 45 cases that were ultimately designated as SIDS.     

The effects of sarin-like and soman-like organophosphorus agents on MAPK and JNK in rat brains

One sarin-like and one soman-like organophosphorus agent [bis(isopropyl methyl)phosphonate, BIMP and bis(pinacolyl methyl)phosphonate, BPMP] were injected intravenously (iv) in rats. An increase in the tyrosine phosphorylation of several proteins in the cytosol fraction of the brain was observed. Activation of c-Jun N-terminal kinase (JNK) and slight activation of mitogen-activated protein kinase (MAPK) in the cytosol were also observed. The activation of these enzymes may be related to the high toxicity of these nerve agents.     

Y chromosomal short tandem repeat (STR) loci in a representative group of males living in South Württemberg: a database for application in forensic medicine

In this study, we resolved the allelic distribution of three Y chromosomal short tandem repeats (STRs), DYS19 (n=218), DYS390 (n=257) and DYS393 (n=215), in a population study of 257 unrelated men living in the area of South Wüerttemberg/Hohenzollern. In DYS19 and in DYS393, five different alleles were discovered, and in DYS390, six different alleles. Forty-nine different haplotypes were found in 202 unrelated male individuals. By investigating each of the three STR systems separately, the most powerful results were found in DYS390, with a PE (power of exclusion) of 0.74, followed by DYS19 (PE: 0.65) and DYS393 (PE: 0.47). Using a combination of two systems (n=202), the PEs ranged from 0.79 (DYS19 and DYS393) to 0.89 (DYS19 and DYS390). The combination of all three STR systems revealed a PE of 0.93.     

Portuguese population and paternity investigation studies with a multiplex PCR--the AmpFlSTR Profiler Plus

A Portuguese Caucasian population of 146 unrelated individuals was studied. DNA samples were amplified by multiplex PCR for D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820 using the AmpFlSTR Profiler Plus PCR Amplification Kit (Perkin-Elmer). All loci met Hardy-Weinberg expectations. Forensic statistical parameters were according to those obtained by other authors. Statistical differences were observed concerning three loci when comparing the Portuguese Caucasian population and an Italian Caucasian population, although these differences mainly concern the less frequent alleles. Eighty-three paternity investigation cases were analysed. Exclusions in between three and nine loci were observed in all the 23 exclusion cases obtained. Most of the non-exclusion cases had probability of paternity > 99.9%. Two cases with an isolated genetic incompatibility between the alleged father and the child were detected, which may indicate probable mutation cases. These results demonstrate that the AmpFlSTR Profiler Plus is a suitable multiplex for paternity investigation in the Portuguese population.     

Fatal intoxication due to dothiepin

An ingestion of an unknown quantity of Harmomed (dothiepin and diazepam) capsules in a suicide is described. The authors report a new and fast method of analysing and determining the dothiepin concentration in postmortem specimens. Quantitation of dothiepin, and its metabolite desmethyldothiepin was performed by ethyl acetate extraction from alkalinized body fluids before GC-MS analysis. The analyses were performed without any complex sample clean-up steps and with little sample material. Postmortem concentrations of dothiepin, desmethyldothiepin, diazepam and desmethyldiazepam in body fluids are given. The proposed method is a rapid procedure for analysis in cases of deliberate poisoning with the antidepressant drug dothiepin.     

A simulation model of tobacco youth access policies

Empirical studies have found that policies aimed at reducing youth access to tobacco have been successful at increasing retail compliance, but their effects on actual tobacco use are mixed. This article presents a model of youth access policies that helps explain the apparently conflicting results in the extant literature, provides a framework for future empirical studies, and suggests implications for public policy. Our model highlights the interaction of components in a well-designed policy, including sufficient compliance checks, penalties, and community involvement. It also illustrates why it will be difficult to eliminate all of youth supply. Nonretail sources, such as borrowing or stealing from parents and siblings and purchasing from older peers through black markets, are an important component of youth supply and become more important as retail access is reduced. The analysis is limited to policies that affect the retail supply of cigarettes but suggests the need for other policies that affect the demand for cigarettes, such as taxes and cessation policies, in order to further reduce youth smoking rates.     

Effect of toluene inhalation on astrocytes and neurotrophic factor in rat brain

Toluene, an abused substance in Japan, is a neurotoxic chemical that has been shown to have neurobehavioral and electrophysiological effects. In previous work, both acute and chronic effects of toluene on cells have been studied extensively. However, although glial cells are thought to play an important role in the survival of neurons in the brain, the effect of toluene on glial cell function has not yet been characterized. To elucidate this, the effect of toluene inhalation on astrocytes in rat brain was examined. Toluene exposure (1500 ppm for 4 h on 4-10 days) augmented glial fibrillary acidic protein (GFAP) immunoreactivity, particularly in the hippocampus and cerebellum. Quantitative analysis showed that toluene inhalation markedly enhanced GFAP expression in the hippocampus and cerebellum. In both regions, proliferating cell nuclear antigen (PCNA) showed no obvious changes, but glutamine synthetase (GS)-immunoreactive cells were markedly increased by toluene exposure. Thus, the elevation of GFAP expression was induced by astrocyte activation rather than by cell proliferation. If toluene exposure activates astrocytes, astrocytes may play a role in the neurophysiological changes observed in toluene intoxication. A neurotrophic factor, basic fibroblast growth factor (b-FGF) was observed immunohistochemically in the capillary vessel walls in the hippocampus and the cerebellum of toluene-intoxicated rats. Basic-FGF may have induced GFAP expression both in the hippocampus and the cerebellum. So, other neurotrophic factors may affect the difference of GFAP elevation between the hippocampus and the cerebellum. These differences may relate to neurobehavioral function of each brain part after toluene exposure.     

Lectin-histochemical detection of degenerative glycoconjugate deposits in human brain

Several lectins were used to study the localization of glycoconjugates in brain of elderly people and patients with Alzheimer type dementia (ATD) and Down's syndrome (DS). Five kinds of degenerated or deposited materials stained clearly by lectins specific to GalNAC, Gal, Fuc, and/or Man were recognized much in ATD and DS, less in elderly peoples, in addition to the binding of the lectins to neurons. (i) Round shape deposits called corpora amylacea (CA) which consisted of various sizes of round material, existed mainly on the surface of cerebral cortex and some in white matter of the brain. They were colored by Alcian blue (AB), Aldehyde fucsin (AF) and periodic acid shiff (PAS) and weakly by Hematoxylin (H), but not by Eosin (B). They showed clear reactivity with lectins specific to GalNAC, Gal, Fuc and Gal-GalNAC. (ii) Amorphous and variform amyloid deposits existed around blood vessels in the white matter were stained by thioflavin and lectins specific to GalNAC, Gal and Fuc, but not with Man specific lectins and PAS, AB, AF and HE. (iii) Another kind of amyloid deposits which showed a similar characteristic to the previous one and were recognized mainly in white matter and independent blood vessels. These deposits were stained by thioflavin but not by PAS, AB, AF and HE and showed good reactivity with lectins specific to GalNAC, Gal, Fuc, Gal-GalNAC, Gal-GIcNAc and Man. The reactivity with lectins specific to Gal, Fuc, and Man was seen in senile plaques (iv) and neurofibrillary tangles (v). Although at present we are unable to explain the origin of these deposits, it is clear from this study that the glycoconjugates form an integral part of the degeneration in the brain. The lectin staining with GS-I is useful in the forensic pathology to diagnose brain disorders at postmortem examination, since these lectin were able to detect five types of degeneration changes and/or deposits.