Reliability of ordinal outcomes in forensic black-box studies.

Forensic science disciplines such as latent print examination, bullet and cartridge case comparisons, and shoeprint analysis, involve subjective decisions by forensic experts throughout the examination process. Most of the decisions involve ordinal categories. Examples include a three-category outcome for latent print comparisons (exclusion, inconclusive, identification) and a seven-category outcome for footwear comparisons (exclusion, indications of non-association, inconclusive, limited association of class characteristics, association of class characteristics, high degree of association, identification). As the results of the forensic examinations of evidence can heavily influence the outcomes of court proceedings, it is important to assess the reliability and accuracy of the underlying decisions. "Black box" studies are the most common approach for assessing the reliability and accuracy of subjective decisions. In these studies, researchers produce evidence samples consisting of a sample of questioned source and a sample of known source where the ground truth (same source or different source) is known. Examiners provide assessments for selected samples using the same approach they would use in actual casework. These studies often have two phases; the first phase comprises of decisions on samples of varying complexities by different examiners, and the second phase involves repeated decisions by the same examiner on a (usually) small subset of samples that were encountered by examiners in the first phase. We provide a statistical method to analyze ordinal decisions from black-box trials with the objective of obtaining inferences for the reliability of these decisions and quantifying the variation in decisions attributable to the examiners, the samples, and statistical interaction effects between examiners and samples. We present simulation studies to judge the performance of the model on data with known parameter values and apply the model to data from a handwritten signature complexity study, a latent fingerprint examination black-box study, and a handwriting comparisons black-box study.

Within-subject changes in methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome.

Background: Adverse early-life experiences (ELA), including poverty, trauma and neglect, affect a majority of the world's children. Whereas the impact of ELA on cognitive and emotional health throughout the lifespan is well-established, it is not clear how distinct types of ELA influence child development, and there are no tools to predict for an individual child their vulnerability or resilience to the consequences of ELAs. Epigenetic markers including DNA-methylation profiles of peripheral cells may encode ELA and provide a predictive outcome marker. However, the rapid dynamic changes in DNA methylation in childhood and the inter-individual variance of the human genome pose barriers to identifying profiles predicting outcomes of ELA exposure. Here, we examined the relation of several dimensions of ELA to changes of DNA methylation, using a longitudinal within-subject design and a high threshold for methylation changes in the hope of mitigating the above challenges. Methods: We analyzed DNA methylation in buccal swab samples collected twice for each of 110 infants: neonatally and at 12 months. We identified CpGs differentially methylated across time, calculated methylation changes for each child, and determined whether several indicators of ELA associated with changes of DNA methylation for individual infants. We then correlated select dimensions of ELA with methylation changes as well as with measures of executive function at age 5 years. We examined for sex differences, and derived a sex-dependent 'impact score' based on sites that most contributed to the methylation changes. Findings: Setting a high threshold for methylation changes, we discovered that changes in methylation between two samples of an individual child reflected age-related trends towards augmented methylation, and also correlated with executive function years later. Among the tested factors and ELA dimensions, including income to needs ratios, maternal sensitivity, body mass index and sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, an interaction was observed between a measure of high early-life unpredictability and methylation changes, in presaging executive function. Interpretation: These findings establish longitudinal, within-subject changes in methylation profiles as a signature of some types of ELA in an individual child. Notably, such changes are detectable beyond the age-associated DNA methylation dynamics. Future studies are required to determine if the methylation profile changes identified here provide a predictive marker of vulnerabilities to poorer cognitive and emotional outcomes.

Early life exposure to unpredictable parental sensory signals shapes cognitive development across three species.

Exposure to early life adversity has long term consequences on cognitive function. Most research has focused on understanding components of early life adversities that contribute to later risk, including poverty, trauma, maltreatment, and neglect. Whereas these factors, in the aggregate, explain a significant proportion of emotional and cognitive problems, there are serious gaps in our ability to identify potential mechanisms by which early life adversities might promote vulnerability or resilience. Here we discuss early life exposure to unpredictable signals from the caretaker as an understudied type of adversity that is amenable to prevention and intervention. We employ a translational approach to discover underlying neurobiological mechanisms by which early life exposure to unpredictable signals sculpts the developing brain. First, we review evidence that exposure to unpredictable signals from the parent during sensitive periods impacts development of neural circuits. Second, we describe a method for characterizing early life patterns of sensory signals across species. Third, we present published and original data illustrating that patterns of maternal care predict memory function in humans, non-human primates, and rodents. Finally, implications are discussed for identifying individuals at risk so that early preventive-intervention can be provided.

Resource scarcity but not maternal separation provokes unpredictable maternal care sequences in mice and both upregulate Crh-associated gene expression in the amygdala.

Early life adversity (ELA) is a major risk factor for the development of pathology, including anxiety disorders. Neurodevelopmental and behavioral outcomes following ELA are multifaceted and are influenced heavily by the type of adversity experienced and sex of the individual experiencing ELA. It remains unclear what properties of ELA portend differential neurobiological risk and the basis of sex-differences for negative outcomes. Predictability of the postnatal environment has emerged as being a core feature supporting development, with the most salient signals deriving from parental care. Predictability of parental care may be a distinguishing feature of different forms of ELA, and the degree of predictability afforded by these manipulations may contribute to the diversity of outcomes observed across models. Further, questions remain as to whether differing levels of predictability may contribute to differential effects on neurodevelopment and expression of genes associated with risk for pathology. Here, we tested the hypothesis that changes in maternal behavior in mice would be contingent on the type of ELA experienced, directly comparing predictability of care in the limited bedding and nesting (LBN) and maternal separation (MS) paradigms. We then tested whether the predictability of the ELA environment altered the expression of corticotropin-releasing hormone (Crh), a sexually-dimorphic neuropeptide that regulates threat-related learning, in the amygdala of male and female mice. The LBN manipulation reliably increased the entropy of maternal care, a measure that indicates lower predictability between sequences of dam behavior. LBN and MS rearing similarly increased the frequency of nest sorties and licking of pups but had mixed effects on other aspects of dam-, pup-, and nest-related behaviors. Increased expression of Crh-related genes was observed in pups that experienced ELA, with gene expression measures showing a significant interaction with sex and type of ELA manipulation. Specifically, MS was associated with increased expression of Crh-related genes in males, but not females, and LBN primarily increased expression of these genes in females, but not males. The present study provides evidence for predictability as a distinguishing feature of models of ELA and demonstrates robust consequences of these differing experience on sex-differences in gene expression critically associated with stress responding and sex differences in risk for pathology.

Quantitative evaluation of AgNORs in bone tumours.

AIMS: Primary tumours of bone present a significant diagnostic and therapeutic challenge at times. Silver stained nucleolar organiser regions (AgNORs) have been widely used in a variety of tissues but with a limited study on bone tumours. Our study was aimed at the evaluation of AgNOR count in various neoplastic lesions of bone. METHODS: : One hundred biopsies of bone lesions were included in this study. Five samples of foetal lumbar vertebrae obtained from foetal autopsies were taken as control. The study included 58 males and 42 females with age ranging from 5 to 70 years. Fifty-two cases were malignant while 48 were benign in nature. Silver staining for nuclear organiser regions was performed according to one-step silver staining technique in these cases. NORs seen as black dots were counted in the nuclei of 100 cells. RESULTS: Our study revealed that the mean count was highest in malignant lesions (4.00+/-0.69) compared with benign lesions (2.16+/-0.43) and normal bone (1.32+/-0.14). Statistically, the AgNOR count showed a significant difference (P<0.001) in all these lesions. CONCLUSIONS: The results of the current study revealed that malignant lesions had a greater mean AgNOR count than benign tumours and the normal bone. Thus, quantification of AgNORs strongly correlates with the type as well as aggressiveness of the bone tumour and is diagnostically useful in tumour differentiation.

Individuality of handwriting.

Motivated by several rulings in United States courts concerning expert testimony in general, and handwriting testimony in particular, we undertook a study to objectively validate the hypothesis that handwriting is individual. Handwriting samples of 1,500 individuals, representative of the U.S. population with respect to gender, age, ethnic groups, etc., were obtained. Analyzing differences in handwriting was done by using computer algorithms for extracting features from scanned images of handwriting. Attributes characteristic of the handwriting were obtained, e.g., line separation, slant, character shapes, etc. These attributes, which are a subset of attributes used by forensic document examiners (FDEs), were used to quantitatively establish individuality by using machine learning approaches. Using global attributes of handwriting and very few characters in the writing, the ability to determine the writer with a high degree of confidence was established. The work is a step towards providing scientific support for admitting handwriting evidence in court. The mathematical approach and the resulting software also have the promise of aiding the FDE.

Morphometric analysis of AgNORs in the lymph node lesions.

Silver stained argyrophilic nucleolar organizer regions (AgNOR) had widely been used for diagnostic as well as prognostic purposes in surgical pathology. Our study was carried out for the quantitative and morphometric analysis of AgNORs in various lymph node lesions. Ten cases each of reactive lymphadenitis and non-Hodgkin's lymphoma (NHL) were included in the present study. Out of 10 cases of NHL, 5 cases each were of Low grade and High grade lymphomas. The morphometric analysis and quantification of AgNORs were curried out using a specific programme of an automatic image analysis Biovis Image measure version 1.0. The results revealed that mean AgNOR count was maximum in high grade lymphoma (5.17 +/- 0.255) when compared with low grade lymphoma (4.78 +/- 0.41) and reactive lymph nodes (2.45 +/- 0.486). Similarly, the mean of total AgNOR area in high grade lymphoma (511.9 +/- 41.52) was highest followed by low grade lymphoma (451.12 +/- 37.1) and reactive lymphadenitis (215 +/- 37). However, the mean of ratio of single AgNOR dot area to nuclear area was lowest in high grade lymphoma (0.0718 +/- 0.01) in comparison to low grade lymphoma (0.0826 +/- 0.0096) and reactive lymph node (0.132 +/- 0.01). Thus, it can be concluded from the present study that different features of AgNOR evaluated morphometrically (AgNOR count, total AgNOR area, AgNOR dot area, ratio of total AgNOR area and single AgNOR area to nuclear area) were significantly altered in various lymph node lesions which may be helpful in differential diagnosis of problematic cases.