PENDULUM--a guideline-based approach to the interpretation of STR mixtures

Several years ago, a theory to interpret mixed DNA profiles was proposed that included a consideration of peak area using the method of least squares. This method of mixture interpretation has not been widely adopted because of the complexity of the associated calculations. Most reporting officers (RO) employ an experience and judgement based approach to the interpretation of mixed DNA profiles. Here we present an approach that has formalised the thinking behind this experience and judgement. This has been written into a computer program package called PENDULUM. The program uses a least squares method to estimate the pre-amplification mixture proportion for two potential contributors. It then calculates the heterozygous balance for all of the potential sets of genotypes. A list of "possible" genotypes is generated using a set of heuristic rules. External to the programme the candidate genotypes may then be used to formulate likelihood ratios (LR) that are based on alternative casework propositions. The system does not represent a black box approach; rather it has been integrated into the method currently used by the reporting officers at the Forensic Science Service (FSS). The time saved in automating routine calculations associated with mixtures analysis is significant. In addition, the computer program assists in unifying reporting processes, thereby improving the consistency of reporting.     

Validation of a 21-locus autosomal SNP multiplex for forensic identification purposes

A single nucleotide polymorphism (SNP) multiplex has been developed to analyse highly degraded and low copy number (LCN) DNA template, i.e. <100 pg, for scenarios including mass disaster identification. The multiplex consists of 20 autosomal non-coding loci plus Amelogenin for sex determination, amplified in a single tube PCR reaction and visualised on the Applied Biosystems 3100 capillary electrophoresis (CE) system. Allele-specific primers tailed with shared universal tag sequences were designed to speed multiplex design and balance the amplification efficiencies of all loci through the use of a single reverse and two differentially labelled allele denoting forward universal primers. As the multiplex is intended for use with samples too degraded for conventional profiling, a computer program was specifically developed to aid interpretation. Critical factors taken into account by the software include empirically determined extremes of heterozygous imbalance (Hb) and the drop-out threshold (Ht) defined as the maximum peak height of a surviving heterozygous allele, where its partner may have dropped out. The discrimination power of the system is estimated at 1 in 4.5 million, using a White Caucasian population database. Comparisons using artificially degraded samples profiled with both the SNP multiplex and AMPFISTR SGM plus (Applied Biosystems) demonstrated a greater likelihood of obtaining a profile using SNPs for certain sample types. Saliva stains degraded for 147 days generated an 81% complete SNP profile whilst short tandem repeats (STRs) were only 18% complete; similarly blood degraded for 243 days produced full SNP profiles but only 9% with STRs. Reproducibility studies showed concordance between SNP profiles for different sample types, such as blood, saliva, semen and hairs, for the same individual, both within and between different DNA extracts.     

A genetic basis for anomalous band patterns encountered during DNA STR profiling

Since 1995 the Forensic Science Service (FSS) has carried out DNA profiling of reference samples for the UK National DNA Database and in forensic casework using two multiplex STR profiling systems. During this period, profiles with anomalous banding patterns, although comparatively rare, have been encountered regularly. The FSS has collected instances of triallelic patterns and aberrant diallelic patterns. A systematic examination of these patterns has provided insight into their underlying genetic cause. The triallelic patterns could be classified into two types based on the relative intensities of their component alleles. In the Type 1 pattern the alleles were of uneven intensity, whereas in the Type 2 pattern, all three alleles were of even intensity. Evidence is presented that the more frequent Type 1 pattern is the result of somatic mutation at a heterozygous locus, and the Type 2 pattern is the result of a localized chromosomal rearrangement at a heterozygous locus. Directly from the Type 1 pattern, it was possible to deduce the size difference between the progenitor and mutated allele. All mutational changes were found to be multiples of four nucleotides, suggesting the loss or addition of one or more tetrameric repeat units. Aberrant diallelic patterns were identified by analysts due to an unexpectedly large difference in intensity between alleles at a heterozygous locus. While some of these diallelic patterns are likely caused by the same genetic phenomena described above occurring at a homozygous locus, others are demonstrated to be caused by a mutation in the primer binding sequence, leading to a reduction in amplification efficiency of one allele. It is concluded that based on a visual inspection of a profile, it is possible to infer a likely genetic basis directly from the triallelic pattern. By contrast, the aberrant diallelic patterns can be due to any one of a number of possible genetic effects.     

Y-STR analysis on DNA mixture samples—Results of a collaborative project of the ENFSI DNA Working Group

The ENFSI (European Network of Forensic Science Institutes) DNA Working Group undertook a collaborative project on Y-STR typing of DNA mixture samples that were centrally prepared and thoroughly tested prior to the shipment. Four commercial Y-STR typing kits (Y-Filer, Applied Biosystems, Foster City, CA, USA; Argus Y Nonaplex, Biotype, Dresden, Germany; Powerplex Y, Promega, Madison, WI, USA; and DYSplex-3, SERAC, Bad Homburg, Germany) were used for the amplification of the mixture samples. The results of the study showed a striking inter-laboratory difference of kit performance as determined from the peak heights of the obtained Y-STR genotypes. Variation in quantity and quality of the shipped DNA can be excluded as reason for the observed differences because both samples and shipping conditions were found to be reproducible in an earlier study. The results suggest that in some cases a laboratory-specific optimization process is indicated to reach a comparable sensitivity for the analysis of minute amounts of DNA.     

Can ministries of health support primary health care? Some suggestions for structural reorganization and planning

Patrick Vaughan is Reader in health care epidemiology, Gill Walt is Lecturer in health policy and Anne Mills is Lecturer in health economics, at the Evaluation and Planning Centre for Health Care, London School of Hygiene and Tropical Medicine, Gower Street, London WC1, United Kingdom. A previous version of this paper was prepared for the Commonwealth Secretariat, London, for the Conference of Commonwealth Health Ministers held in Ottawa, Canada, in October 1983.     

Autorisierung. Eine wissenschafts- und wirtschaftssoziologische Perspektive auf geistiges Eigentum

Property obliges??and intellectual property entails responsibility about the knowledge produced. The theoretical concept of authorization enables the development of a genuinely sociological perspective of intellectual property. Based on this perspective of intellectual property, it is possible to introduce new aspects in the current and for the advanced knowledge capitalism central debate. The concept of authorization is based on the observation that??from the perspective of knowledge users??it is very difficult (if not impossible) to assess in advance the quality of knowledge and knowledge goods, like for example drugs. This uncertainty entails the consumers?? demand for authorization for an attribution of responsibility. The need of authorization is caused by the extent of insecurity and it exists independently from the aspiration of intellectual property by a company or person (for the time being, the debate struggles only with the last problem). Starting from there, the article examines the question how authorization is being established in the social field. Thereby, it is not only contentious whether or not knowledge should be commercialized or is open access. It is also contentious to which extend the power of definition should be hierarchically monopolized or egalitarianly distributed. The theoretical perspective will be illustrated with a case study on the authorization of seed??the latter being an economic resource which is of elementary importance for human life.     

Lethal Connections: The Determinants of Network Connections in the Provisional Irish Republican Army, 1970–1998

Using stochastic methods we illustrate that the Provisional Irish Republican Army's (PIRA) network is clustered along three primary dimensions: (a) brigade affiliation, (b) whether the member participated in violent activities, and (c) task/role within PIRA. While most brigades tended to foster connections within the brigade (that is, “closure”), the tendency to do so varied across the organization. Members who engaged with violent activities were far more likely to connect with each other; in later periods there is polarization into those who engage in violent activities and those who do not. Across brigades, those who engage in a particular task and role (improvised explosive device [IED] constructor, IED planter, gunman, robber/kidnapper/drug smuggler/hijacker) are more likely to connect with others who do the same task or play the same role than with other members who fulfill other roles. Standard forms of homophily (that is, the tendency to make connections with people who are similar in terms of demography or status) play a very weak role in explaining which members interact with one another. Finally, our analysis illustrates clear patterns of relational change that correspond to changes in the formal structures that PIRA's leadership promoted.