A novel method for pair-matching using three-dimensional digital models of bone:mesh-to-mesh value comparison

The commingling of human remains often hinders forensic/physical anthropologists during the identification process, as there are limited methods to accurately sort these remains. This study investigates a new method for pair-matching, a common individualization technique, which uses digital three-dimensional models of bone: mesh-to-mesh value comparison (MVC). The MVC method digitally compares the entire three-dimensional geometry of two bones at once to produce a single value to indicate their similarity. Two different versions of this method, one manual and the other automated, were created and then tested for how well they accurately pair-matched humeri. Each version was assessed using sensitivity and specificity. The manual mesh-to-mesh value comparison method was 100 % sensitive and 100 % specific. The automated mesh-to-mesh value comparison method was 95 % sensitive and 60 % specific. Our results indicate that the mesh-to-mesh value comparison method overall is a powerful new tool for accurately pair-matching commingled skeletal elements, although the automated version still needs improvement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00414-016-1334-3) contains supplementary material, which is available to authorized users

Exploring the functionality of mesh-to-mesh value comparison in pair-matching and its application to fragmentary remains

SIMPLE SUMMARY: Forensic anthropologists often face the task of analysing a mixed group of skeletal remains or matching a solitary bone with the rest of a skeleton to determine if it belongs to the same individual. One of the best ways to do this is by pair-matching left and right bones of the same type. Common pair-matching methods experience issues such as high levels of subjectivity, lack of reliability, or expensive cost of implementation. This study explores the application of the relatively new method, mesh-to-mesh value comparison (MVC), which matches paired bones based on morphological shape to determine the likelihood that they derive from the same individual. This study sought to expand on the success found in past publications using MVC and to see how well it performed on a sample of clavicles, a bone known for having a high degree of bilateral variability, of 80 modern Turkish individuals. This study also explored whether MVC can reliably match fragmented bones to their intact counterpart. Results show MVC successfully matched 88.8% of paired clavicles and suggest the method continues to be a promising avenue for pair-matching that is not affected by ancestry and may be applicable to fragmented remains with further study. ABSTRACT: Many cases encountered by forensic anthropologists involve commingled remains or isolated elements. Common methods for analysing these contexts are characterised by limitations such as high degrees of subjectivity, high cost of application, or low proven accuracy. This study sought to test mesh-to-mesh value comparison (MCV), a relatively new method for pair-matching skeletal elements, to validate the claims that the technique is unaffected by age, sex and pathology. The sample consisted of 160 three-dimensional clavicle models created from computed tomography (CT) scans of a contemporary Turkish population. Additionally, this research explored the application of MVC to match fragmented elements to their intact counterparts by creating a sample of 480 simulated fragments, consisting of three different types based on the region of the bone they originate from. For comparing whole clavicles, this resulted in a sensitivity value of 87.6% and specificity of 90.9% using ROC analysis comparing clavicles. For the fragment comparisons, each type was compared to the entire clavicles of the opposite side. The results included a range of sensitivity values from 81.3% to 87.6%. Overall results are promising and the MVC technique seems to be a useful technique for matching paired elements that can be accurately applied to a Modern Turkish sample

Metric variation of the tibia in the Mediterranean: implications in forensic identification

Ancestry estimation from skeletal remains is a challenging task, but essential for the creation of a complete biological profile. As such, the study of human variation between populations is important for the fields of biological and forensic anthropology, as well as medicine. Cranial and dental morphological variation have traditionally been linked to geographic affinity resulting in several methods of ancestry estimation, while the postcranial skeleton has been systematically neglected. The current study explores metric variation of the tibia in six Mediterranean populations and its validity in estimating ancestry in the Mediterranean. The study sample includes 909 individuals (470 males and 439 females) from Cyprus, Greece, Italy, Spain, Portugal and Turkey. The sample was divided in two subsamples: a reference and a validation sample. Multinomial regression models were created based on the reference sample and then applied to validation sample. The first model used three variables and resulted in 57% and 56% accuracy for the two samples respectively, while the second model (6 variables) resulted in 80% and 74% respectively. Classification between groups ranged from 28% to 95% for the reference sample and from 15% to 91% for the validation sample. The highest classification accuracy was noted for the Greek sample (95% and 90% for the reference and validation sample respectively), followed by the Turkish sample (74% and 78% respectively). The Spanish, Portuguese and Italian samples presented greater morphological overlap which resulted in lower classification accuracies. The results indicate that although the tibia presents considerable variation amongst neighbour populations is not suitable as a sole skeletal element to separate all groups successfully. A combination of different skeletal elements may be required in order to achieve the levels of reliability required for forensic applications

TNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade

Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system. Besides their intrinsic immune stimulating properties, the adenoviruses used here are armed to express tumor necrosis factor alpha (TNFa) and interleukin-2 (IL-2). These cytokines result in immunological danger signaling and multiple appealing T-cell effects, including trafficking, activation and propagation. When these viruses were injected into B16.OVA melanoma tumors in animals concomitantly receiving programmed cell-death protein 1 (PD-1) blocking antibodies both tumor growth control (p <0.0001) and overall survival (p <0.01) were improved. In this set-up, the addition of adoptive cell therapy with OT-I lymphocytes did not increase efficacy further. When virus injections were initiated before antibody treatment in a prime-boost approach, 100% of tumors regressed completely and all mice survived. Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells. These preclinical studies provide the rationale and schedule for a clinical trial where oncolytic adenovirus coding for TNFa and IL-2 (TILT-123) is used in melanoma patients receiving an anti-PD-1 antibody.Peer reviewe

Scrutinizing assortative mating in birds

It is often claimed that pair bonds preferentially form between individuals that resemble one another. Such assortative mating appears to be widespread throughout the animal kingdom. Yet it is unclear whether the apparent ubiquity of assortative mating arises primarily from mate choice ("like attracts like"), which can be constrained by same-sex competition for mates;from spatial or temporal separation;or from observer, reporting, publication, or search bias. Here, based on a conventional literature search, we find compelling meta-analytical evidence for size-assortative mating in birds (r = 0.178, 95% CI 0.142-0.215, 83 species, 35,591 pairs). However, our analyses reveal that this effect vanishes gradually with increased control of confounding factors. Specifically, the effect size decreased by 42% when we used previously unpublished data from nine long-term field studies, i.e., data free of reporting and publication bias (r = 0.103, 95% CI 0.074-0.132, eight species, 16,611 pairs). Moreover, in those data, assortative mating effectively disappeared when both partners were measured by independent observers or separately in space and time (mean r = 0.018, 95% CI -0.016-0.057). Likewise, we also found no evidence for assortative mating in a direct experimental test for mutual mate choice in captive populations of Zebra finches (r = -0.020, 95% CI -0.148-0.107, 1,414 pairs). These results highlight the importance of unpublished data in generating unbiased meta-analytical conclusions and suggest that the apparent ubiquity of assortative mating reported in the literature is overestimated and may not be driven by mate choice or mating competition for preferred mates

Responses to Bacteria, Virus, and Malaria Distinguish the Etiology of Pediatric Clinical Pneumonia

RationalePlasma-detectable biomarkers that rapidly and accurately diagnose bacterial infections in children with suspected pneumonia could reduce the morbidity of respiratory disease and decrease the unnecessary use of antibiotic therapy.ObjectivesUsing 56 markers measured in a multiplexed immunoassay, we sought to identify proteins and protein combinations that could discriminate bacterial from viral or malarial diagnoses.MethodsWe selected 80 patients with clinically diagnosed pneumonia (as defined by the World Health Organization) who also met criteria for bacterial, viral, or malarial infection based on clinical, radiographic, and laboratory results. Ten healthy community control subjects were enrolled to assess marker reliability. Patients were subdivided into two sets: one for identifying potential markers and another for validating them.Measurements and main resultsThree proteins (haptoglobin, tumor necrosis factor receptor 2 or IL-10, and tissue inhibitor of metalloproteinases 1) were identified that, when combined through a classification tree signature, accurately classified patients into bacterial, malarial, and viral etiologies and misclassified only one patient with bacterial pneumonia from the validation set. The overall sensitivity and specificity of this signature for the bacterial diagnosis were 96 and 86%, respectively. Alternative combinations of markers with comparable accuracy were selected by support vector machine and regression models and included haptoglobin, IL-10, and creatine kinase-MB.ConclusionsCombinations of plasma proteins accurately identified children with a respiratory syndrome who were likely to have bacterial infections and who would benefit from antibiotic therapy. When used in conjunction with malaria diagnostic tests, they may improve diagnostic specificity and simplify treatment decisions for clinicians

Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease

Background: Coeliac disease ( CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3' of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3' to C alpha-1 in CD patients compared to a control population was analysed. Methods: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR). Results: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio ( OR) showed that those with 2/2 and 2/4 ( OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD ( OR 0.52, P = 0.01). Conclusions: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis

Climate change drives microevolution in a wild bird

To ensure long-term persistence, organisms must adapt to climate change, but an evolutionary response to a quantified selection pressure driven by climate change has not been empirically demonstrated in a wild population. Here, we show that pheomelanin-based plumage colouration in tawny owls is a highly heritable trait, consistent with a simple Mendelian pattern of brown (dark) dominance over grey (pale). We show that strong viability selection against the brown morph occurs, but only under snow-rich winters. As winter conditions became milder in the last decades, selection against the brown morph diminished. Concurrent with this reduced selection, the frequency of brown morphs increased rapidly in our study population during the last 28 years and nationwide during the last 48 years. Hence, we show the first evidence that recent climate change alters natural selection in a wild population leading to a microevolutionary response, which demonstrates the ability of wild populations to evolve in response to climate change

Complex nature of SNP genotype effects on gene expression in primary human leucocytes

<p>Abstract</p> <p>Background</p> <p>Genome wide association studies have been hugely successful in identifying disease risk variants, yet most variants do not lead to coding changes and how variants influence biological function is usually unknown.</p> <p>Methods</p> <p>We correlated gene expression and genetic variation in untouched primary leucocytes (n = 110) from individuals with celiac disease – a common condition with multiple risk variants identified. We compared our observations with an EBV-transformed HapMap B cell line dataset (n = 90), and performed a meta-analysis to increase power to detect non-tissue specific effects.</p> <p>Results</p> <p>In celiac peripheral blood, 2,315 SNP variants influenced gene expression at 765 different transcripts (< 250 kb from SNP, at FDR = 0.05, <it>cis </it>expression quantitative trait loci, eQTLs). 135 of the detected SNP-probe effects (reflecting 51 unique probes) were also detected in a HapMap B cell line published dataset, all with effects in the same allelic direction. Overall gene expression differences within the two datasets predominantly explain the limited overlap in observed <it>cis</it>-eQTLs. Celiac associated risk variants from two regions, containing genes <it>IL18RAP </it>and <it>CCR3</it>, showed significant <it>cis </it>genotype-expression correlations in the peripheral blood but not in the B cell line datasets. We identified 14 genes where a SNP affected the expression of different probes within the same gene, but in opposite allelic directions. By incorporating genetic variation in co-expression analyses, functional relationships between genes can be more significantly detected.</p> <p>Conclusion</p> <p>In conclusion, the complex nature of genotypic effects in human populations makes the use of a relevant tissue, large datasets, and analysis of different exons essential to enable the identification of the function for many genetic risk variants in common diseases.</p

Biomarkers to Distinguish Bacterial From Viral Pediatric Clinical Pneumonia in a Malaria-Endemic Setting.

BACKGROUND: Differential etiologies of pediatric acute febrile respiratory illness pose challenges for all populations globally, but especially in malaria-endemic settings because the pathogens responsible overlap in clinical presentation and frequently occur together. Rapid identification of bacterial pneumonia with high-quality diagnostic tools would enable appropriate, point-of-care antibiotic treatment. Current diagnostics are insufficient, and the discovery and development of new tools is needed. We report a unique biomarker signature identified in blood samples to accomplish this. METHODS: Blood samples from 195 pediatric Mozambican patients with clinical pneumonia were analyzed with an aptamer-based, high-dynamic-range, quantitative assay (~1200 proteins). We identified new biomarkers using a training set of samples from patients with established bacterial, viral, or malarial pneumonia. Proteins with significantly variable abundance across etiologies (false discovery rate 90% sensitivity and >80% specificity, regardless of number of pathogen classes. Bacterial pneumonia was strongly associated with neutrophil markers-in particular, degranulation including HP, LCN2, LTF, MPO, MMP8, PGLYRP1, RETN, SERPINA1, S100A9, and SLPI. CONCLUSIONS: Blood protein signatures highly associated with neutrophil biology reliably differentiated bacterial pneumonia from other causes. With appropriate technology, these markers could provide the basis for a rapid diagnostic for field-based triage for antibiotic treatment of pediatric pneumonia