Medical Imaging Compatibility of Magnesium- and Iron-Based Bioresorbable Flow Diverters.

BACKGROUND AND PURPOSE: Bioresorbable flow diverters are under development to mitigate complications associated with conventional flow-diverter technology. One proposed advantage is the ability to reduce metal-induced artifacts in follow-up medical imaging. In the current work, the medical imaging compatibility of magnesium- and iron-based bioresorbable flow diverters is assessed relative to an FDA-approved control in phantom models. MATERIALS AND METHODS: Bioresorbable flow diverters, primarily composed of braided magnesium or antiferromagnetic iron alloy wires, were compared with an FDA-approved control flow diverter. The devices were assessed for MR imaging safety in terms of magnetically induced force and radiofrequency heating using 1.5T, 3T, and 7T field strength clinical scanners. The devices were deployed in phantom models, and metal-induced image artifacts were assessed in the 3 MR imaging scanners and a clinical CT scanner following clinical scan protocols; device visibility was assessed under fluoroscopy. RESULTS: The magnesium-based bioresorbable flow diverter, iron-based bioresorbable flow diverter, and the control device all demonstrated MR imaging safety in terms of magnetically induced force and radiofrequency heating at all 3 field strengths. The bioresorbable flow diverters did not elicit excessive MR imaging artifacts at any field strength relative to the control. Furthermore, the bioresorbable flow diverters appeared to reduce blooming artifacts in CT relative to the control. The iron-based bioresorbable flow diverter and control device were visible under standard fluoroscopy. CONCLUSIONS: We have demonstrated the baseline medical imaging compatibility of magnesium and antiferromagnetic iron alloy bioresorbable flow diverters. Future work will evaluate the medical imaging characteristics of the bioresorbable flow diverters in large-animal models.

Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication.

Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.

Variable kinship patterns in Neolithic Anatolia revealed by ancient genomes.

The social organization of the first fully sedentary societies that emerged during the Neolithic period in Southwest Asia remains enigmatic,1 mainly because material culture studies provide limited insight into this issue. However, because Neolithic Anatolian communities often buried their dead beneath domestic buildings,2 household composition and social structure can be studied through these human remains. Here, we describe genetic relatedness among co-burials associated with domestic buildings in Neolithic Anatolia using 59 ancient genomes, including 22 new genomes from Asikli Höyük and Çatalhöyük. We infer pedigree relationships by simultaneously analyzing multiple types of information, including autosomal and X chromosome kinship coefficients, maternal markers, and radiocarbon dating. In two early Neolithic villages dating to the 9th and 8th millennia BCE, Asikli Höyük and Boncuklu, we discover that siblings and parent-offspring pairings were frequent within domestic structures, which provides the first direct indication of close genetic relationships among co-burials. In contrast, in the 7th millennium BCE sites of Çatalhöyük and Barcin, where we study subadults interred within and around houses, we find close genetic relatives to be rare. Hence, genetic relatedness may not have played a major role in the choice of burial location at these latter two sites, at least for subadults. This supports the hypothesis that in Çatalhöyük,3-5 and possibly in some other Neolithic communities, domestic structures may have served as burial location for social units incorporating biologically unrelated individuals. Our results underscore the diversity of kin structures in Neolithic communities during this important phase of sociocultural development.

Cross-sectional imaging and laparoscopic findings of diaphragmatic mesothelial cysts.

AIM: To present cross-sectional imaging, surgical findings, and follow-up results of diaphragmatic mesothelial cysts. MATERIALS AND METHODS: Radiological findings for location, size, shape, and internal structure of cysts were reviewed retrospectively. For patients that underwent surgery, surgical reports and laparoscopy images were reviewed. In conservatively managed patients, changes in size and imaging findings of the cyst were assessed during follow-up visits. RESULTS: A total of 13 paediatric cases with an imaging and/or pathological diagnosis of diaphragmatic mesothelial cyst were identified. In all cases, the cystic lesions were located between the diaphragm and the posterolateral aspect of the right lobe of the liver. Eleven lesions (84.6%) had a bi-lobulate shape. Eight of these cases underwent laparoscopic cyst aspiration/unroofing. The postoperative course was uneventful and there were no cases of recurrence. The remaining five cases were managed conservatively with follow-up available in four cases. In three cases (75%), there was reduction in the size of the cysts with a mean volume reduction of 55%. CONCLUSION: Diaphragmatic mesothelial cysts are congenital cystic lesions that are usually detected incidentally. A common pitfall is incorrect interpretation of the lesion as a hepatic cyst. Conservative management with imaging follow-up can be adopted in asymptomatic cases with typical imaging findings.

Strong population structure in a species manipulated by humans since the Neolithic: the European fallow deer (Dama dama dama).

Species that have been translocated and otherwise manipulated by humans may show patterns of population structure that reflect those interactions. At the same time, natural processes shape populations, including behavioural characteristics like dispersal potential and breeding system. In Europe, a key factor is the geography and history of climate change through the Pleistocene. During glacial maxima throughout that period, species in Europe with temperate distributions were forced south, becoming distributed among the isolated peninsulas represented by Anatolia, Italy and Iberia. Understanding modern patterns of diversity depends on understanding these historical population dynamics. Traditionally, European fallow deer (Dama dama dama) are thought to have been restricted to refugia in Anatolia and possibly Sicily and the Balkans. However, the distribution of this species was also greatly influenced by human-mediated translocations. We focus on fallow deer to better understand the relative influence of these natural and anthropogenic processes. We compared modern fallow deer putative populations across a broad geographic range using microsatellite and mitochondrial DNA loci. The results revealed highly insular populations, depauperate of genetic variation and significantly differentiated from each other. This is consistent with the expectations of drift acting on populations founded by small numbers of individuals, and reflects known founder populations in the north. However, there was also evidence for differentiation among (but not within) physically isolated regions in the south, including Iberia. In those regions we find evidence for a stronger influence from natural processes than may be expected for a species with such strong, known anthropogenic influence.

Comparison of three different primer sets for sexing birds.

Because many bird species are monomorphic or only sexually dimorphic in adult stages, it is difficult to determine their sexes, which may cause significant problems in population and conservation studies. DNA-based sexing relies on the chromodomain helicase DNA binding ( CHD) gene located on the W chromosome and its homolog on the Z chromosome, giving distinct banding patterns on agarose gel as a result of length differences in intronic regions within this gene. We used 3 specific primer sets, CHD1F/CHD1R, 2550F/2718R, and P2/P8, for sex determination of 230 samples from 77 avian species. We report here the records for 70 of those species analyzed using the CHD1F/CHD1R primer set, and 49 species using 2550F/2718R, and 46 species using P2/P8. CHD1F/CHD1R PCR products on agarose gel generally showed an apparent single band in males and 2 bands in females, but the products of 2550F/2718R (61%) and P2/P8 (42%) showed distinct banding patterns for separate bird orders. However, when PCR products of these last 2 primer pairs labeled with fluorescent dye were run in a capillary gel and detected using a DNA analyzer, P2/P8 gave 2 distinguishable peaks in females, whereas 2550F/2718R results remained the same. DNA sexing with any of those 3 primer sets can be used for all sexually monomorphic avian taxa although the primer sets should be compared before choosing the most efficient one for molecular sexing of the studied species.

Factors predicting iliac metastasis and overall survival in malignant melanoma of the lower extremities.

BACKGROUND: To analyse the patient-related, disease-related and treatment-related factors in a group of melanoma patients to assess their impact on iliac metastasis and on overall survival. METHODS: Medical records of thirty-nine patients with lower extremity malignant melanoma were retrospectively reviewed to confirm all of the clinical data. Age and gender were recorded as patient-related factors. Tumor location, size, histology, ulceration status, and TNM stage, Breslow thickness, Clark level, presence of inguinal LN metastases, and locoregional metastases (local recurrences, in transit metastases and regional LN metastases) were evaluated as disease-related factors. Type of surgery (en block excision of primary tumor, en block excision of primary tumor and inguinal lymph node dissection, en block excision of primary tumor and ilioinguinal lymph node dissection) and postoperative chemotherapy were taken into account as treatment-related factors. RESULTS: The presence of inguinal lymph node metastases was significantly associated with iliac metastasis (p = 0.015). Tumor size (p = 0.046), tumor TNM stage (p = 0.009), Breslow thickness (p = 0.033), Clark level (p = 0.029), presence of in transit metastases (p = 0.010) and postoperative chemotherapy (p = 0.002) has been related to impaired overall survival rate. CONCLUSIONS: Therapeutic lymph node dissection appears to carry a small but definite therapeutic benefit. Selection of appropriate patients for the more extensive procedure would be ideal, but at present there are no well proven selection criteria. The authors advocate therapeutic dissection when the inguinal lymph nodes are involved.

Digitally adjusting chromogenic dye proportions in brightfield microscopy images.

We present an algorithm to adjust the contrast of individual dyes from colour (red-green-blue) images of dye mixtures. Our technique is based on first decomposing the colour image into individual dye components, then adjusting each of the dye components and finally mixing the individual dyes to generate colour images. Specifically in this paper, we digitally adjust the staining proportions of hematoxylin and eosin (H&E) chromogenic dyes in tissue images. We formulate the physical dye absorption process as a non-negative mixing equation, and solve the individual components using non-negative matrix factorisation (NMF). Our NMF formulation includes camera dark current in addition to the mixing proportions and the individual H and E components. The novelty of our approach is to adjust the dye proportions while preserving the color of nonlinear dye interactions, such as pigments and red blood cells. In this paper we present results for only H&E images, our technique can easily be extended to other staining techniques.

Quantitative metric profiles capture three-dimensional temporospatial architecture to discriminate cellular functional states.

BACKGROUND: Computational analysis of tissue structure reveals sub-visual differences in tissue functional states by extracting quantitative signature features that establish a diagnostic profile. Incomplete and/or inaccurate profiles contribute to misdiagnosis. METHODS: In order to create more complete tissue structure profiles, we adapted our cell-graph method for extracting quantitative features from histopathology images to now capture temporospatial traits of three-dimensional collagen hydrogel cell cultures. Cell-graphs were proposed to characterize the spatial organization between the cells in tissues by exploiting graph theory wherein the nuclei of the cells constitute the nodes and the approximate adjacency of cells are represented with edges. We chose 11 different cell types representing non-tumorigenic, pre-cancerous, and malignant states from multiple tissue origins. RESULTS: We built cell-graphs from the cellular hydrogel images and computed a large set of features describing the structural characteristics captured by the graphs over time. Using three-mode tensor analysis, we identified the five most significant features (metrics) that capture the compactness, clustering, and spatial uniformity of the 3D architectural changes for each cell type throughout the time course. Importantly, four of these metrics are also the discriminative features for our histopathology data from our previous studies. CONCLUSIONS: Together, these descriptive metrics provide rigorous quantitative representations of image information that other image analysis methods do not. Examining the changes in these five metrics allowed us to easily discriminate between all 11 cell types, whereas differences from visual examination of the images are not as apparent. These results demonstrate that application of the cell-graph technique to 3D image data yields discriminative metrics that have the potential to improve the accuracy of image-based tissue profiles, and thus improve the detection and diagnosis of disease.

Phylogeographic patterns of genetic diversity in eastern Mediterranean water frogs have been determined by geological processes and climate change in the Late Cenozoic.

AIM: Our aims were to assess the phylogeographic patterns of genetic diversity in eastern Mediterranean water frogs and to estimate divergence times using different geological scenarios. We related divergence times to past geological events and discuss the relevance of our data for the systematics of eastern Mediterranean water frogs. LOCATION: The eastern Mediterranean region. METHODS: Genetic diversity and divergence were calculated using sequences of two protein-coding mitochondrial (mt) genes: ND2 (1038 bp, 119 sequences) and ND3 (340 bp, 612 sequences). Divergence times were estimated in a Bayesian framework under four geological scenarios representing alternative possible geological histories for the eastern Mediterranean. We then compared the different scenarios using Bayes factors and additional geological data. RESULTS: Extensive genetic diversity in mtDNA divides eastern Mediterranean water frogs into six main haplogroups (MHG). Three MHGs were identified on the Anatolian mainland; the most widespread MHG with the highest diversity is distributed from western Anatolia to the northern shore of the Caspian Sea, including the type locality of Pelophylax ridibundus. The other two Anatolian MHGs are restricted to south-eastern Turkey, occupying localities west and east of the Amanos mountain range. One of the remaining three MHGs is restricted to Cyprus; a second to the Levant; the third was found in the distribution area of European lake frogs (P. ridibundus group), including the Balkans. MAIN CONCLUSIONS: Based on geological evidence and estimates of genetic divergence we hypothesize that the water frogs of Cyprus have been isolated from the Anatolian mainland populations since the end of the Messinian salinity crisis (MSC), i.e. since c. 5.5-5.3 Ma, while our divergence time estimates indicate that the isolation of Crete from the mainland populations (Peloponnese, Anatolia) most likely pre-dates the MSC. The observed rates of divergence imply a time window of c. 1.6-1.1 million years for diversification of the largest Anatolian MHG; divergence between the two other Anatolian MHGs may have begun about 3.0 Ma, apparently as a result of uplift of the Amanos Mountains. Our mtDNA data suggest that the Anatolian water frogs and frogs from Cyprus represent several undescribed species.

Quantification of spatial parameters in 3D cellular constructs using graph theory.

Multispectral three-dimensional (3D) imaging provides spatial information for biological structures that cannot be measured by traditional methods. This work presents a method of tracking 3D biological structures to quantify changes over time using graph theory. Cell-graphs were generated based on the pairwise distances, in 3D-Euclidean space, between nuclei during collagen I gel compaction. From these graphs quantitative features are extracted that measure both the global topography and the frequently occurring local structures of the "tissue constructs." The feature trends can be controlled by manipulating compaction through cell density and are significant when compared to random graphs. This work presents a novel methodology to track a simple 3D biological event and quantitatively analyze the underlying structural change. Further application of this method will allow for the study of complex biological problems that require the quantification of temporal-spatial information in 3D and establish a new paradigm in understanding structure-function relationships.

Investigation of the effect of exhaust particles on ocular blood flow in highway toll collectors using color Doppler ultrasonography.

PURPOSE: To investigate the effect of exhaust particles on orbital blood flow velocity of the ophthalmic artery, central retinal artery, and posterior ciliary artery by color Doppler ultrasonography in highway toll collectors. MATERIAL AND METHODS: Color Doppler imaging was used to measure the peak-systolic and end-diastolic flow velocities and resistivity indices of the ophthalmic artery, central retinal artery, and posterior ciliary artery in 20 toll collectors and 20 controls. RESULTS: Both the peak-systolic and the end-diastolic flow velocities were decreased in the ophthalmic artery, central retinal artery, and posterior ciliary artery, and the resistivity index was increased in the central retinal artery in toll collectors when compared with control groups. Results were considered statistically significant if P<0.05. CONCLUSION: It was determined that the effect of exhaust particles reduced ocular blood flow velocity in toll collectors as measured by color duplex Doppler ultrasonography.