Are forensic scientists too risk averse?

Fingerprint examiners maintain decision thresholds that represent the amount of evidence required for an identification or exclusion conclusion. As measured by error rate studies (Proc Natl Acad Sci USA. 2011;108(19):7733-8), these decision thresholds currently exhibit a preference for preventing erroneous identification errors at the expense of preventing erroneous exclusion errors. The goal of this study is to measure the decision thresholds for both fingerprint examiners and members of the general public, to determine whether examiners are more risk averse than potential jury members. To externally measure these decision thresholds, subjects manipulated decision criteria in a web-based visualization that reflects the trade-offs between erroneous identification decisions and erroneous exclusion decisions. Data from fingerprint examiners and the general public were compared to determine whether both groups have similar values as expressed by the placement of the decision criteria. The results of this study show that fingerprint examiners are more risk averse than members of the general public, although they align with error rate studies of fingerprint examiners. Demographic data demonstrate those factors that may contribute to differences in decision criterion placement, both between the two groups and between individuals within a group. The experimental methods provide a rich framework for measuring, interpreting, and responding to the values of society as applied to forensic decision-making.

The Utility of Expanded Conclusion Scales During Latent Print Examinations.

During fingerprint comparisons, a latent print examiner visually compares two impressions to determine whether or not they originated from the same source. They consider the amount of perceived detail in agreement or disagreement and accumulate evidence toward same source and different sources propositions. This evidence is then mapped to one of three conclusions: Identification, Inconclusive, or Exclusion. A limitation of this 3-conclusion scale is it can lose information when translating the conclusion from the internal strength-of-evidence value to one of only three possible conclusions. An alternative scale with two additional values, support for different sources and support for common sources, has been proposed by the Friction Ridge Subcommittee of OSAC. The expanded scale could lead to more investigative leads but could produce complex trade-offs in both correct and erroneous identifications. The aim of the present study was to determine the consequences of a shift to expanded conclusion scales in latent print comparisons. Latent print examiners each completed 60 comparisons using one of the two scales, and the resulting data were modeled using signal detection theory to measure whether the expanded scale changed the threshold for an "Identification" conclusion. When using the expanded scale, examiners became more risk-averse when making "Identification" decisions and tended to transition both the weaker Identification and stronger Inconclusive responses to the "Support for Common Source" statement. The results demonstrate the utility of an expanded conclusion scale and also provide guidance for the adoption of these or similar scales.

Predicting Ischemic Risk Using Blood Oxygen Level-Dependent MRI in Children with Moyamoya.

BACKGROUND AND PURPOSE: Moyamoya is a progressive steno-occlusive arteriopathy. MR imaging assessment of cerebrovascular reactivity can be performed by measuring the blood oxygen level-dependent cerebrovascular reactivity response to vasoactive stimuli. Our objective was to determine whether negative blood oxygen level-dependent cerebrovascular reactivity status is predictive of ischemic events in childhood moyamoya. MATERIALS AND METHODS: We conducted a retrospective study of a consecutive cohort of children with moyamoya who underwent assessment of blood oxygen level-dependent cerebrovascular reactivity. The charts of patients with written informed consent were reviewed for the occurrence of arterial ischemic stroke, transient ischemic attack, or silent infarcts. We used logistic regression to calculate the OR and 95% CI for ischemic events based on steal status. Hazard ratios for ischemic events based on age at blood oxygen level-dependent cerebrovascular reactivity imaging, sex, and moyamoya etiology were calculated using Cox hazards models. RESULTS: Thirty-seven children (21 female; median age, 10.7 years; interquartile range, 7.5-14.7 years) were followed for a median of 28.8 months (interquartile range, 13.7-84.1 months). Eleven (30%) had ischemic events, 82% of which were TIA without infarcts. Steal was present in 15 of 16 (93.8%) hemispheres in which ischemic events occurred versus 25 of 58 (43.1%) ischemic-free hemispheres (OR = 19.8; 95% CI, 2.5-160; P = .005). Children with idiopathic moyamoya were at significantly greater risk of ischemic events (hazard ratio, 3.71; 95% CI, 1.1-12.8; P = .037). CONCLUSIONS: Our study demonstrates that idiopathic moyamoya and the presence of steal are independently associated with ischemic events. The use of blood oxygen level-dependent cerebrovascular reactivity could potentially assist in the selection of patients for revascularization surgery and the direction of therapy in children with moyamoya.

Quantifying the ossification of the carpus in skeletal age estimation: Radiographic standards for Australian subadults.

An evaluation of the development of a child's skeleton and estimation of bone age provides an insight into a child's overall maturation. This study aimed to introduce a contemporary method for assessing bone age of Australian children using formulae incorporating carpal areal measurements. The standards introduced in this study can be used to assess the developmental status of Australian children who may be affected by growth-related illnesses. Additionally, in situations where the living age of a subadult is unknown, methodologies to accurately estimate age are required, particularly in the Western world where knowledge of the age of an individual is necessary for legal reasons. The sample consisted of retrospective hand and wrist radiographs acquired from 541 children (females: 246, males: 295) aged from birth to 20 years. Using the DICOM viewer Weasis, the carpal area ratio (B.Ar/T.Ar) was calculated for each individual radiograph by measuring the carpal bone area (B.Ar) and total tissue area of the carpus (T.Ar). A changepoint regression model demonstrated that the model constructed in this study was the most accurate in the younger age groups and was able to accurately determine whether a child was under 12 years if female and 13 years if male. A rapid acceleration of growth was observed at approximately 12-13 years in our sample, which may represent the onset of the pubertal growth spurt; this resulted in a high data variance and low model prediction accuracy in female and male children older than 12 and 13 years, respectively.

Holistic processing of fingerprints by expert forensic examiners.

Holistic processing is often characterized as a process by which objects are perceived as a whole rather than a compilation of individual features. This mechanism may play an important role in the development of perceptual expertise because it allows for rapid integration across image regions. The present work explores whether holistic processing is present in latent fingerprint examiners, who compare fingerprints collected from crime scenes against a set of standards taken from a suspect. We adapted a composite task widely used in the face recognition and perceptual expertise literatures, in which participants were asked to match only a particular half of a fingerprint with a previous image while ignoring the other half. We tested both experts and novices, using both upright and inverted fingerprints. For upright fingerprints, we found weak evidence for holistic processing, but with no differences between experts and novices with respect to holistic processing. For inverted fingerprints, we found stronger evidence of holistic processing, with weak evidence for differences between experts and novices. These relatively weak holistic processing effects contrast with robust evidence for holistic processing with faces and with objects in other domains of perceptual expertise. The data constrain models of holistic processing by demonstrating that latent fingerprint experts and novices may not substantively differ in terms of the amount of holistic processing and that inverted stimuli actually produced more evidence for holistic processing than upright stimuli. Important differences between the present fingerprint stimuli and those in the literature include the lack of verbal labels for experts and the absence of strong vertical asymmetries, both of which might contribute to stronger holistic processing signatures in other stimulus domains.

Oxytocin Neurones: Intrinsic Mechanisms Governing the Regularity of Spiking Activity.

Oxytocin neurones of the rat supraoptic nucleus are osmoresponsive and, with all other things being equal, they fire at a mean rate that is proportional to the plasma sodium concentration. However, individual spike times are governed by highly stochastic events, namely the random occurrences of excitatory synaptic inputs, the probability of which is increased by increasing extracellular osmotic pressure. Accordingly, interspike intervals (ISIs) are very irregular. In the present study, we show, by statistical analyses of firing patterns in oxytocin neurones, that the mean firing rate as measured in bins of a few seconds is more regular than expected from the variability of ISIs. This is consistent with an intrinsic activity-dependent negative-feedback mechanism. To test this, we compared observed neuronal firing patterns with firing patterns generated by a leaky integrate-and-fire model neurone, modified to exhibit activity-dependent mechanisms known to be present in oxytocin neurones. The presence of a prolonged afterhyperpolarisation (AHP) was critical for the ability to mimic the observed regularisation of mean firing rate, although we also had to add a depolarising afterpotential (DAP; sometimes called an afterdepolarisation) to the model to match the observed ISI distributions. We tested this model by comparing its behaviour with the behaviour of oxytocin neurones exposed to apamin, a blocker of the medium AHP. Good fits indicate that the medium AHP actively contributes to the firing patterns of oxytocin neurones during non-bursting activity, and that oxytocin neurones generally express a DAP, even though this is usually masked by superposition of a larger AHP.

The potential for epigenetic analysis of paediatric CNS tumours to improve diagnosis, treatment and prognosis.

Tumours of central nervous system (CNS) origin are the second most prevalent group of cancers in children, yet account for the majority of childhood cancer-related deaths. Such tumours show diverse location, cell type of origin, disease course and long-term outcome, both across and within tumour types, making treatment problematic and contributing to the relatively modest progress in reducing mortality over recent decades. As technological advances begin to reveal the genetic landscape of all cancers, it is becoming increasingly clear that genetic disruption represents only one 'layer' of molecular disruption associated with disease aetiology. Obtaining a full understanding of tumour behaviour requires an understanding of the cellular and molecular pathways disrupted during tumourigenesis, particularly in relation to gene expression. The utility of such an approach has allowed stratification of cancers such as medulloblastoma into subgroups based on molecular features, with potential to refine risk prediction. Given that epigenetic disruption is a universal feature of all human cancers, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore the clinical trajectory, of tumours. An integrated approach to build a molecular 'signature' of individual tumours that incorporates traditional morphological and demographic information, genetic and transcriptome analysis, in addition to epigenomics (DNA methylation and non-coding RNA analysis), offers tremendous promise to (i) inform treatment approach, (ii) facilitate accurate early identification (preferably at diagnosis) of variable risk groups (both good and poor prognosis groups), and (iii) track disease progression in childhood CNS tumours.

Information coding in vasopressin neurons--the role of asynchronous bistable burst firing.

The task of the vasopressin system is homeostasis, a type of process which is fundamental to the brain's regulation of the body, exists in many different systems, and is vital to health and survival. Many illnesses are related to the dysfunction of homeostatic systems, including high blood pressure, obesity and diabetes. Beyond the vasopressin system's own importance, in regulating osmotic pressure, it presents an accessible model where we can learn how the features of homeostatic systems generally relate to their function, and potentially develop treatments. The vasopressin system is an important model system in neuroscience because it presents an accessible system in which to investigate the function and importance of, for example, dendritic release and burst firing, both of which are found in many systems of the brain. We have only recently begun to understand the contribution of dendritic release to neuronal function and information processing. Burst firing has most commonly been associated with rhythm generation; in this system it clearly plays a different role, still to be understood fully.

Dural infantile hemangioma masquerading as a skull vault lesion.

We describe a case of intracranial dural IH initially diagnosed as a primary skull vault lesion hemangioma due to associated focal hyperostosis. Histopathologic examination of the dural component confirmed IH. The case is discussed in the context of IH within the neural axis.

Upper limb motor function in young adults with spina bifida and hydrocephalus.

OBJECTIVE: The objective of the study was to measure upper limb motor function in young adults with spina bifida meningomyelocele (SBM) and typically developing age peers. METHOD: Participants were 26 young adults with SBM, with a Verbal or Performance IQ score of at least 70 on the Wechsler scales, and 27 age- and gender-matched controls. Four upper limb motor function tasks were performed under four different visual and cognitive challenge conditions. Motor independence was assessed by questionnaire. RESULTS: Fewer SBM than control participants obtained perfect posture and rebound scores. The SBM group performed less accurately and was more disrupted by cognitive challenge than controls on limb dysmetria tasks. The SBM group was slower than controls on the diadochokinesis task. Adaptive motor independence was related to one upper limb motor task, arm posture, and upper rather than lower spinal lesions were associated with less motor independence. CONCLUSIONS: Young adults with SBM have significant limitations in upper limb function and are more disrupted by some challenges while performing upper limb motor tasks. Within the group of young adults with SBM, upper spinal lesions compromise motor independence more than lower spinal lesions.

A new method of spike modelling and interval analysis.

Here we develop a new model of spike firing, based on the leaky integrate and fire model, modified to simulate afterpotentials. We also develop new analysis techniques, applying these to recorded and model generated data in order to make a comparative analysis and develop the model as a hypothesis for the functional components of the neuron. The model is based in this first instance on hypothalamic oxytocin neurons. We demonstrate how model parameters and cell properties relate to features observed in inter-spike intervals histograms, and the limits of these in being able to detect patterning features in spike recordings. A new technique, spike train analysis, is able to detect previously unobserved patterning, showing a dependence of spike intervals on previous firing activity. This effect is reproduced in the model by adding the small amplitude but long lasting after hyper-polarising potential (AHP). A fit measure based on log likelihood is used to compare model generated data to recorded spike intervals, taking account of interval dependence on previous activity. This measure is used with the simplex multiple parameter search algorithm to develop an automated method for fitting the model to recorded data.

Mathematical modelling in neuroendocrinology.

In neuroendocrinology, mathematical modelling is about formalising our understanding of the behaviour of the complex biological systems with which we deal. Formulating our explanations mathematically ensures their logical consistency, and makes them open to structured analysis; it is a stringent test of their intellectual coherence. In addition, however, modellers are seeking to extend our understanding in new ways, by seeking novel, simple explanations for complex behaviour. Here we discuss some styles of modelling as they have been applied to neuroendocrine systems, and discuss some of their strengths and limitations.

Absence of retroviral vector-mediated transformation of gene-modified T cells after long-term engraftment in mice.

There is considerable concern regarding the transforming potential of retroviral vectors currently used for gene therapy, with evidence that retroviral integration can lead to leukemia in recipients of gene-modified stem cells. However, it is not clear whether retroviral-mediated transduction of T cells can lead to malignancy. We transduced mouse T cells with a Moloney murine retroviral gene construct and transferred them into congenic mice, which were preconditioned to enhance the engraftment of transferred T cells. Recipients were then observed long-term for evidence of cancer. Transferred T cells persisted in mice throughout life at levels up to 17% with gene copy numbers up to 5.89 x 10(5) per million splenocytes. Mice receiving gene-modified T cells developed tumors at a similar rate as control mice that did not receive T cells, and tumors in both groups of mice were of a similar range of histologies. Hematological malignancies comprised approximately 60% of cancers, and the remaining cancers consisted largely of carcinomas. Importantly, the incidence of lymphomas was similar in both groups of mice, and no lymphomas were found to be of donor T-cell origin. This study indicates that the use of retroviral vectors to transduce T cells does not lead to malignant transformation.

Health-related quality of life in a cohort of adult patients with mild hemophilia A.

OBJECTIVES: To compare the health-related quality of life among adult males affected with mild hemophilia A due to the same mutation (Val2016ala) to that of unaffected age and sex matched controls from the same general population. METHODS: The Short-Form 36 (SF-36) and Health Assessment Questionnaire (HAQ) were used to measure health-related quality of life and physical function. Other measures included bleeding history, a measure of joint damage, body mass index, age, and viral infection status. Cross-sectional data were collected through research clinics and a retrospective chart audit over a two-year period. RESULTS AND CONCLUSIONS: The study included 47 affected males and 33 controls. The affected males had a higher level of co-morbidity, prior bleeding, and existing joint damage than controls. With the exception of the social function and health transition scales, mean scores for each of the SF-36 domains were worse among affected males. Mean differences were more than a clinically important five points in five of eight domains, with the general health scale showing more than a 10-point difference. Despite the degree of difference noted, only two of the differences were statistically significant (general health and role emotional scales) because of the small sample size and considerable individual variation in SF-36 scale scores. Multiple regression analyses suggested existing joint damage and presence of heart disease as the strongest associates of lower physical health-related quality of life. Joint damage in turn was partly related to prior hemarthroses. Compared to the Canadian population, affected males had lower scores in six out of eight SF-36 domains as well as the physical component summary score. There were no significant differences found in the HAQ scores between the two groups. So-called mild hemophilia A was associated with a negative effect on physical health-related quality of life, contributed to by joint damage as a result of prior bleeding.

Fourier transform infrared imaging as a method for detection of HLA class I expression in melanoma without the use of antibody.

Human leukocyte antigen (HLA) class I expression in melanoma is usually assessed using immunohistochemical staining. Here we report on the use of Fourier transform infrared (FTIR) hyperspectral imaging, a method widely used in two-dimensional analysis of chemical components, to study HLA class I expression in tissue. Two-dimensional cluster colour images derived from unsupervised hierarchical cluster analysis of FTIR hyperspectral data on melanoma sections were compared with consecutive sections that were immunohistochemically stained for class I expression. HLA-class-I-positive and -negative areas were differentiated by FTIR cluster images in all eight melanoma sections investigated without the need for antibody attachment. FTIR imaging enables the distinction of HLA-class-I-positive from class-I-negative areas in melanoma. This method is accurate, rapid and cost-effective.

PPARG locus haplotype variation and exacerbations in asthma.

The peroxisome proliferator-activated receptor gamma (PPARgamma) regulates inflammation and may play a role in asthma. Using mouthwash-derived DNA and clinical interviews and measurements, we investigated the association of previously characterized single-nucleotide polymorphisms in the PPARG gene (Pro12Ala, C1431T, and C-681G) with asthma exacerbations in patients aged 3-22 years (n=569). The common homozygous haplotype combination of the Pro12 and C1431 alleles was associated with increased risk for asthma exacerbations (ProC, odds ratio (OR) 1.87, 95% confidence interval 1.25-2.79; P=0.002). The ProC genotype was associated with increased school absences (OR 1.82, 95% confidence interval 1.21-2.76; P=0.004) and hospital admissions (OR 2.32, 95% confidence interval 1.18-4.58; P=0.015) over the preceding 6 months. The population-attributable risk of this genotype was 33%. Common genetic variation at the PPARG locus may play an important role in modulating the long-term control of asthma in children and young adults.

Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol.

BACKGROUND: The homozygous presence of the arginine-16 variant of the beta(2) adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting beta(2) agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting beta(2) agonists. METHODS: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. RESULTS: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. CONCLUSIONS: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.