Reporting likelihood ratio for casework in firearm evidence identification.

Likelihood ratio (LR) plays an important role in estimating the weight of evidence in firearm evidence identifications. LR is computed from a statistical model including the distribution of the known-matching (KM or within) and known-nonmatching (KNM or between) comparison scores. Current LR procedures rely on KM/KNM scores from existing reference firearm toolmark data sets or alternatively from generating a set of test fires using multiple firearms. Both procedures may contain theoretical or practical issues which may hinder the LR procedures from reporting an unbiased LR estimation in casework. In this paper, a reference data set was established from a set of firearms, each test-fired two cartridge cases, resulting in a basic data set and a control data set. The congruent matching cells (CMC) method was used to generate CMC scores that are used to fit in the KM/KNM statistical distributions for LR estimation. In the initial test, 130 firearms from eight manufacturers were used for generating a reference data set consisting of 260 cartridge cases representing 130 KM and 8385 KNM pairwise breech face images. Test results showed that the KM and KNM distribution intersect at CMC = 2, which is equivalent to LR = 1 (equally to support both the prosecutor and the defense propositions). When the CMC threshold is increased to 6 or more, the LR values are higher than a million, which can provide extremely strong support to the conclusion of the same firearm (or the prosecutor's proposition) in the casework of firearm evidence identification.

Living in the shadow of Lynch Syndrome: British women's accounts.

In this paper we explore accounts of eight British women living with Lynch Syndrome: a hereditary syndrome that increases the risk of developing bowel and gynecological cancers. We collected data via semi-structured interviews and analyzed them using Interpretative Phenomenological Analysis. Two themes, 'It's Up to Us': The Lynch Patient Experience; and 'The Biggest Challenge': The Lynch Parent Experience, illustrate the experiential burden and emotional labor of living with Lynch Syndrome. We theorize our analysis through Corbin and Strauss's concept of 'Health Work', and Hochschild's concept of 'Emotion Work'. Recommendations for clinical care and familial support are discussed.

Virtual image standard (VIS) for performance evaluation of the congruent matching cells (CMC) algorithms in firearm evidence identifications.

The congruent matching cells (CMC) method was invented at the National Institute of Standards and Technology (NIST) in 2012 for automatic and objective firearm evidence identifications and estimation of the weight of evidence in firearm evidence identifications. Since 2013, five CMC algorithms have been developed at NIST. In this paper, the virtual image standard (VIS) is proposed through trimming and stitching KNM images for quantitative performance evaluations of different CMC algorithms. The evaluation criteria include the correlation accuracy (both the CMC numbers and distribution pattern), correlation efficiency, false positive (FP) error rate, and the maximum separation of known matching (KM) and known non-matching (KNM) image pairs. The VIS composes correlation cells from different KNM images, which can provide a ground truth for verifying the CMC numbers, distribution patterns, and FP errors. By identifying three groups of VIS, the Convergence CMC algorithm showed superior performances for the future casework in firearm evidence identifications. Lastly, the success of this study suggests that the VIS could also be used to optimize the correlation parameters, to develop and test new CMC algorithms, and evaluate the performance before it is put into use for firearm examiner's casework.

A dysbiotic microbiome promotes head and neck squamous cell carcinoma.

Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.

Evaluating Likelihood Ratio (LR) for firearm evidence identifications in forensic science based on the Congruent Matching Cells (CMC) method.

Firearm evidence identification has been challenged by the 2008 and 2009 National Research Council (NRC) reports and by legal proceedings on its fundamental assumptions, its procedure involving subjective interpretations, and the lack of a statistical foundation for evaluation of error rates or other measures for the weight of evidence. To address these challenges, researchers of the National Institute of Standards and Technology (NIST) recently developed a Congruent Matching Cells (CMC) method for automatic and objective firearm evidence identification and quantitative error rate evaluation. Based on the CMC method, a likelihood ratio (LR) procedure is proposed in this paper aiming to provide a scientific basis for firearm evidence identification and a method for evaluation of the weight of evidence. The initial LR evaluations using two sets of 9mm cartridge cases' breech face impression images with different sample sizes, imaging methods and ammunition showed that for all the declared identifications of the tested 2D and 3D image pairs, the evaluated LRs for the least favorable scenario were well above an order of 106, which provides Extremely Strong Support for a prosecution proposition (e.g. a same-source proposition) in a Bayesian frame. The LR evaluations also showed that for all the declared exclusions of the tested 3D image pairs, the evaluated LRs for the least favorable scenario were above an order of 102, which provides Moderately Strong Support for a defense proposition (e.g. a different-source proposition) in a Bayesian frame.

Metacognitive Awareness Scale, Domain Specific (MCAS-DS): Assessing Metacognitive Awareness During Raven's Progressive Matrices.

Metacognition, the cognition about cognition, is closely linked to intelligence and therefore understanding the metacognitive processes underlying intelligence test performance, specifically on Raven's Progressive Matrices, could help advance the knowledge about intelligence. The measurement of metacognition, is often done using domain-general offline questionnaires or domain-specific online think-aloud protocols. This study aimed to investigate the relationship between metacognitive awareness and intelligence via the design and use of a novel Meta-Cognitive Awareness Scale - Domain Specific (MCAS-DS) that encourages reflection of task strategy processes. This domain-specific scale was first constructed to measure participants' awareness of their own metacognition linked to Raven's Progressive Matrices (SPM). Following discriminatory index and Exploratory Factor Analysis, a 15-item scale was derived. Exploratory Factor Analysis showed five factors: Awareness of Engagement in Self-Monitoring, Awareness of Own Ability, Awareness of Responding Speed/Time, Awareness of Alternative Solutions and Awareness of Requisite Problem-Solving Resources. The intelligence level of ninety-eight adults was then estimated using Raven's Standard Progressive Matrices. Participants also completed the MCAS-DS, and further items that examined their test-taking behavior and Confidence level. Metacognitive awareness was positively correlated to standardized IQ scores derived from the SPM whilst Over-Confidence derived using the Confidence level measure was negatively correlated to SPM. Despite some limitations, this study shows promise for elucidating the relationship between metacognitive awareness and intelligence using the task-specific scale.

Pilot study on deformed bullet correlation.

Most studies on bullet identification address test fired bullets that have near pristine striated marks on the land engraved areas (LEAs). However, in case work, bullets found at a crime scene may be severely deformed or fragmented. The resulting missing, expanded, or distorted LEA striations can cause challenges in toolmark comparisons performed by examiners or algorithms. In this paper, an image reconstruction procedure is proposed that, in combination with the Congruent Matching Profile Segments (CMPS) profile comparison method, facilitates the algorithmic correlation of deformed bullets. Initial validation tests were conducted using 57 bullets, with varying degrees of fragmentation or deformation, that were fired from the same 9mm Luger caliber Luger pistol. The bullets spanned 7 different ammunition brands. The CMPS method was applied to correlate the LEA striation profiles extracted from LEA topography images that were corrected for pattern distortion. 15 bullet LEAs, out of 250 bullet LEAs that could be measured, had major distortions. Two sets of comparison tests were conducted, corresponding to a same source and specific source scenario: 1) comparison of the severely distorted LEAs with a near-pristine reference bullet, before and after image reconstruction, and 2) inter comparisons of distorted LEAs, before and after reconstruction. The reconstruction process significantly improved the correlation results when dealing with distorted bullet LEAs. In general, the improvement was larger for samples with relatively large deformation and good striation visibility. Samples with approximately parallel striations tend to have less improvement of CMPS results after profile reconstruction since the CMPS method itself can correct certain scale errors.

Distinct roles of PIK3CA in the enrichment and maintenance of cancer stem cells in head and neck squamous cell carcinoma.

Recurrence and metastasis are the major causes of mortality in head and neck squamous cell carcinoma (HNSCC). It is suggested that cancer stem cells (CSCs) play pivotal roles in recurrence and metastasis. Thus, a greater understanding of the mechanisms of CSC regulation may provide opportunities to develop novel therapies for improving survival by controlling recurrence or metastasis. Here, we report that overexpression of the gene encoding the catalytic subunit of PI3K (PIK3CA), the most frequently amplified oncogene in HNSCC, promotes epithelial-to-mesenchymal transition and enriches the CSC population. However, PIK3CA is not required to maintain these traits and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway paradoxically promotes CSC population. Molecular analysis revealed that overexpression of PIK3CA activates multiple receptor tyrosine kinases (RTKs), in which ephrin receptors (Ephs), tropomyosin receptor kinases (TRK) and mast/stem cell growth factor receptor (c-Kit) contribute to maintain CSC population. Accordingly, simultaneous inhibition of these RTKs using a multi-kinase inhibitor ponatinib has a superior effect at eliminating the CSC population and reduces metastasis of PIK3CA-overexpressing HNSCC cells. Our result suggests that co-targeting of Ephs, TRKs and the c-Kit pathway may be effective at eliminating the PI3K-independent CSC population, thereby providing potential targets for future development of a novel anti-CSC therapeutic approach for HNSCC patients, particularly for patients with PIK3CA amplification.

Fired bullet signature correlation using the Congruent Matching Profile Segments (CMPS) method.

We introduce the Congruent Matching Profile Segments (CMPS) method for objective comparison of striated tool marks and apply it to bullet signature correlations. The method is derived from the congruent matching cell (CMC) method developed for the comparison of impressed tool marks. The proposed method is designed to increase comparison accuracy by addressing the comparison challenges caused by striae profiles with different lateral scales, varying vertical (height) scales, and sections that are poorly marked or have little to no similarity. Instead of correlating the entire profiles extracted from striated tool marks, the method divides one of the compared profiles into segments. Each segment is then correlated with the other profile. The CMPS method uses the normalized cross-correlation function with multiple correlation peak inspection to determine the number of profile segments that have both significant topography similarity and a congruent registration position. Initial tests were performed on the land engraved areas (LEAs) of 35 bullets fired from 10 consecutively manufactured pistol barrels. The results show clear separation between the CMPS scores of the 549 known non-matching (KNM) LEA profiles and the 46 known matching (KM) LEA profiles. These results are an improvement over those obtained using the correlation coefficient score of whole profiles. The large number of CMPS segment correlations may facilitate a statistical approach to error rate estimations.

CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression.

Evasion of the host immune responses is critical for both persistent human papillomavirus (HPV) infection and associated cancer progression. We have previously shown that expression of the homeostatic chemokine CXCL14 is significantly downregulated by the HPV oncoprotein E7 during cancer progression. Restoration of CXCL14 expression in HPV-positive head and neck cancer (HNC) cells dramatically suppresses tumor growth and increases survival through an immune-dependent mechanism in mice. Although CXCL14 recruits natural killer (NK) and T cells to the tumor microenvironment, the mechanism by which CXCL14 mediates tumor suppression through NK and/or T cells remained undefined. Here we report that CD8+ T cells are required for CXCL14-mediated tumor suppression. Using a CD8+ T-cell receptor transgenic model, we show that the CXCL14-mediated antitumor CD8+ T-cell responses require antigen specificity. Interestingly, CXCL14 expression restores major histocompatibility complex class I (MHC-I) expression on HPV-positive HNC cells downregulated by HPV, and knockdown of MHC-I expression in HNC cells results in loss of tumor suppression even with CXCL14 expression. These results suggest that CXCL14 enacts antitumor immunity through restoration of MHC-I expression on tumor cells and promoting antigen-specific CD8+ T-cell responses to suppress HPV-positive HNC.

The Role of MicroRNAs in Recurrence and Metastasis of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) affects 650,000 people worldwide and has a dismal 50% 5-year survival rate. Recurrence and metastasis are believed the two most important factors causing this high mortality. Understanding the biological process and the underlying mechanisms of recurrence and metastasis is critical to develop novel and effective treatment, which is expected to improve patients' survival of HNSCC. MicroRNAs are small, non-coding nucleotides that regulate gene expression at the transcriptional and post-transcriptional level. Oncogenic and tumor-suppressive microRNAs have shown to regulate nearly every step of recurrence and metastasis, ranging from migration and invasion, epithelial-mesenchymal transition (EMT), anoikis, to gain of cancer stem cell property. This review encompasses an overview of microRNAs involved in these processes. The recent advances of utilizing microRNA as biomarkers and targets for treatment, particularly on controlling recurrence and metastasis are also reviewed.

Cooperation Between Pten and Smad4 in Murine Salivary Gland Tumor Formation and Progression.

Salivary gland tumor (SGT) is a rare tumor type, which exhibits broad-spectrum phenotypic, biological, and clinical heterogeneity. Currently, the molecular mechanisms that cause SGT pathogenesis remain poorly understood. A lack of animal models that faithfully recapitulate the naturally occurring process of human SGTs has hampered research progress on this field. In this report, we developed an inducible keratin 5-driven conditional knockout mouse model to delete gene(s) of interest in murine salivary gland upon local RU486 delivery. We have deleted two major tumor suppressors, Pten, a negative regulator of the PI3K pathway, and Smad4, the central signaling mediator of TGFß pathway, in the murine salivary gland. Our results have shown that deletion of either Pten or Smad4 in murine salivary gland resulted in pleomorphic adenomas, the most common tumor in human SGT patients. Deletion of both Pten and Smad4 in murine salivary gland developed several malignancies, with salivary adenoid cystic carcinoma (SACC) being the most frequently seen. Molecular characterization showed that SACC exhibited mTOR activation and TGFß1 overexpression. Examination of human SGT clinical samples revealed that loss of Pten and Smad4 is common in human SACC samples, particularly in the most aggressive solid form, and is correlated with survival of SACC patients, highlighting the human relevance of the murine models. In summary, our results offer significant insight into synergistic role of Pten and Smad4 in SGT, providing a rationale for targeting mTOR and/or TGFß signaling to control SGT formation and progression.

Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma.

Background: To identify aberrant promoter methylation of genomic loci encoding microRNA (mgmiR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate a biomarker panel of mgmiRs to improve the diagnostic accuracy of HNSCC in tissues and saliva. Methods: Methylation of promoter regions of mgmiR candidates was initially screened using HNSCC and control cell lines and further selected using HNSCC and control tissues by quantitative methylation-specific PCR (qMS-PCR). We then examined a panel of seven mgmiRs for validation in an expanded cohort including 189 HNSCC and 92 non-HNSCC controls. Saliva from 86 pre-treatment HNSCC patients and 108 non-HNSCC controls was also examined using this panel of seven mgmiRs to assess the potentials of clinical utilization. Results: Among the 315 screened mgmiRs, 12 mgmiRs were significantly increased in HNSCC cell lines compared to control cell lines. Seven out of the 12 mgmiRs, i.e., mgmiR9-1, mgmiR124-1, mgmiR124-2, mgmiR124-3, mgmiR129-2, mgmiR137, and mgmiR148a, were further found to significantly increase in HNSCC tumor tissues compared to control tissues. Using multivariable logistic regression with dichotomized variables, a combination of the seven mgmiRs had sensitivity and specificity of 92.6 and 92.4% in tissues and 76.7 and 86.1% in saliva, respectively. Area under the receiver operating curve for this panel was 0.97 in tissue and 0.93 in saliva. This model was validated by independent bootstrap validation and random forest analysis. Conclusions: mgmiR biomarkers represent a novel and promising screening tool, and the seven-mgmiR panel is able to robustly detect HNSCC in both patient tissue and saliva.

Salivary Gland Cancer Patient-Derived Xenografts Enable Characterization of Cancer Stem Cells and New Gene Events Associated with Tumor Progression.

Purpose: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however, current models are limited both in their availability and suitability to characterize these rare cells.Experimental Design: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient. Patient and PDX samples were analyzed by RNA-seq and Exome-seq. Sphere formation potential and in vivo tumorigenicity was assessed by sorting for Aldefluor (ALDH) activity and CD44-expressing subpopulations.Results: For successive MEC relapses we found a time-dependent increase in CSCs (ALDH+CD44high), increasing from 0.2% to 4.5% (P=0.033), but more importantly we observed an increase in individual CSC sphere formation and tumorigenic potential. A 50% increase in mutational burden was documented in subsequent MEC tumors, and this was associated with increased expression of tumor-promoting genes (MT1E, LGR5, and LEF1), decreased expression of tumor-suppressor genes (CDKN2B, SIK1, and TP53), and higher expression of CSC-related proteins such as SOX2, MYC, and ALDH1A1. Finally, genomic analyses identified a novel NFIB-MTFR2 fusion in an ACC tumor and confirmed previously reported fusions (NTRK3-ETV6 and MYB-NFIB)Conclusions: Sequential MEC PDX models preserved key patient features and enabled the identification of genetic events putatively contributing to increases in both CSC proportion and intrinsic tumorigenicity, which mirrored the patient's clinical course. Clin Cancer Res; 24(12); 2935-43. ©2018 AACR.

Estimating error rates for firearm evidence identifications in forensic science.

Estimating error rates for firearm evidence identification is a fundamental challenge in forensic science. This paper describes the recently developed congruent matching cells (CMC) method for image comparisons, its application to firearm evidence identification, and its usage and initial tests for error rate estimation. The CMC method divides compared topography images into correlation cells. Four identification parameters are defined for quantifying both the topography similarity of the correlated cell pairs and the pattern congruency of the registered cell locations. A declared match requires a significant number of CMCs, i.e., cell pairs that meet all similarity and congruency requirements. Initial testing on breech face impressions of a set of 40 cartridge cases fired with consecutively manufactured pistol slides showed wide separation between the distributions of CMC numbers observed for known matching and known non-matching image pairs. Another test on 95 cartridge cases from a different set of slides manufactured by the same process also yielded widely separated distributions. The test results were used to develop two statistical models for the probability mass function of CMC correlation scores. The models were applied to develop a framework for estimating cumulative false positive and false negative error rates and individual error rates of declared matches and non-matches for this population of breech face impressions. The prospect for applying the models to large populations and realistic case work is also discussed. The CMC method can provide a statistical foundation for estimating error rates in firearm evidence identifications, thus emulating methods used for forensic identification of DNA evidence.

A Normalized Congruent Matching Area Method for the Correlation of Breech Face Impression Images.

The congruent matching cells (CMC) method was invented at the National Institute of Standards and Technology (NIST) for firearm evidence identification and error rate estimation. The CMC method divides the correlated image pairs into cells and uses four parameters to quantify topography similarity and pattern congruency of the correlated cell pairs in firearm breech face impressions on fired cartridge cases. A preliminary conservative numerical identification criterion of C = 6 CMCs was suggested for identifying images of cartridge cases fired from the same firearm. The CMC method was validated by correlations using both three-dimensional (3D) topography images and two-dimensional (2D) optical images from a set of 40 cartridge cases fired from a firearm set composed of 10 consecutively manufactured pistol slides. However, in the original CMC method, due to the difference in the effective data area of the correlated cells, final CMCs obtained from an image pair presented different data quantity (or validity level), and thus the empirical criterion C = 6 CMCs did not remain optimal for identification when the correlated cell size changed. In this study, a normalized congruent matching area (NCMA) method that considers the difference in the data area in each correlated cell pair was developed. Based on the NCMA method, an optimal range of cell sizes for breech face identification with granular characteristics was determined. A binomial model was used to fit the known nonmatching NCMA probability distribution Ψ NCMA, and a beta-binomial model was used to fit the known matching NCMA probability distribution Φ NCMA. An experimental improvement in the normalized identification criterion C of around 6 % was observed in the validation tests when the cell sizes were in the optimal range.

Multiple Strokes Associated With Elongation of the Hyoid Bone.

Hyoid bone elongation is an uncommon cause of stroke. Here, we report a case of hyoid bone elongation causing localized trauma to the internal carotid artery, resulting in multiple strokes. A 32-year-old woman presented with unilateral weakness and history of a recent stroke. Imaging revealed the greater horn of the hyoid bone extending between the external and internal carotid with associated thrombus at the carotid bifurcation and acute stroke. Carotid ultrasound demonstrated movement of the hyoid bone in and out of the space between the external carotid artery and internal carotid artery with neck rotation. Treatment involved anticoagulation and partial hyoid bone resection. After resection, the stroke symptoms had not recurred in the patient. Hyoid bone-related carotid injury is an infrequent etiology of stroke, with no established treatment guidelines. Partial hyoid bone resection and antithrombotic therapy are likely a reasonably safe and effective treatment.

A convergence algorithm for correlation of breech face images based on the congruent matching cells (CMC) method.

The Congruent Matching Cells (CMC) method was invented at the National Institute of Standards and Technology (NIST) for accurate firearm evidence identification and error rate estimation. The CMC method is based on the principle of discretization. The toolmark image of the reference sample is divided into correlation cells. Each cell is registered to the cell-sized area of the compared image that has maximum surface topography similarity. For each resulting cell pair, one parameter quantifies the similarity of the cell surface topography and three parameters quantify the pattern congruency of the registration position and orientation. An identification (declared match) requires a significant number of CMCs, that is, cell pairs that meet both similarity and pattern congruency requirements. The use of cell correlations reduces the effects of "invalid regions" in the compared image pairs and increases the correlation accuracy. The identification accuracy of the CMC method can be further improved by considering a feature named "convergence," that is, the tendency of the x-y registration positions of the correlated cell pairs to converge at the correct registration angle when comparing same-source samples at different relative orientations. In this paper, the difference of the convergence feature between known matching (KM) and known non-matching (KNM) image pairs is characterized, based on which an improved algorithm is developed for breech face image correlations using the CMC method. Its advantage is demonstrated by comparison with three existing CMC algorithms using four datasets. The datasets address three different brands of consecutively manufactured pistol slides, with significant differences in the distribution overlap of cell pair topography similarity for KM and KNM image pairs. For the same CMC threshold values, the convergence algorithm demonstrates noticeably improved results by reducing the number of false-positive or false-negative CMCs in a comparison.

Variation in genital human papillomavirus infection prevalence and vaccination coverage among men and women in the USA.

Human papillomavirus (HPV) is the most common sexually transmitted infection that causes majority of anogenital and oropharyngeal cancers. Prophylactic HPV vaccine is available for the primary prevention of cancer and HPV transmission. Here, we are going to discuss the variation of HPV prevalence, HPV vaccination coverage and potential risk factors of men and women, retrieved from the cross-sectional study of the National Health Nutrition Examination Survey, a representative sample of noninstitutionalized, civilian residents in the USA. The overall penile HPV prevalence in men was 45.2% and the high risk oncogenic HPV prevalence defined by DNA testing was 25.1% that appeared to be widespread among all the age groups, which contrasts the vaginal HPV prevalence of 26.8% in women.