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Acute cholecystitis, which is usually associated with gallstones, is one of the commonest surgical causes of emergency hospital admission and may be further complicated by mural necrosis, perforation, and abscess formation. Magnetic resonance imaging (MRI) is increasingly available in the emergency setting. Technically improved equipment and faster acquisition protocols allow excellent tissue contrast and MRI is now an attractive modality for imaging acute abdominal disorders. The use of MRI with MR cholangiopancreatography in the emergency setting provides rapid, noninvasive, and confident diagnosis or exclusion of acute cholecystitis and of coexistent choledocholithiasis. To familiarize the reader with these cross-sectional imaging appearances, this paper reviews MRI findings consistent with uncomplicated cholecystitis. These include gallbladder distension, intraluminal sludge and gallstones, impacted stones obstructing the gallbladder neck or cystic duct, thickening of the gallbladder wall, abnormal signal intensity and edematous stratification, and pericholecystic and perihepatic fluid, plus increased enhancement of the gallbladder wall and adjacent liver parenchyma when intravenous paramagnetic contrast is used. Furthermore, MRI allows prompt detection and comprehensive visualization and characterization of cholecystitis-related complications such as gangrene, perforation, pericholecystic abscess, and intrahepatic fistulization. Some previous literature reports, and our experience, suggest that, when available, MRI should be recommended to provide prompt and efficient triage of patients with suspected cholecystitis and inconclusive clinical, laboratory, and sonographic findings. It facilitates appropriate therapeutic planning, including the timing of surgery (emergency or delayed), approach (laparoscopic or laparotomic), and need for preoperative or intraoperative removal of stone(s) in the common bile duct.

A human skull with mandible from the Ngada District on the island of Flores, Indonesia, is described in order to contribute to the knowledge of variation in cranial architecture, which is important in interpretations of evolutionary cerebralisation. The skull was excavated in 1924 and sent to the National Museum in Copenhagen. The “Copenhagen Flores” (CF) male skull is radiocarbon-dated and of modern age. The cranium is small, but larger than e.g. Liang Bua skull (LB1) in every measurement. The (CT-scan based) cranial capacity of 1258 ml is normal for modern humans, but somewhat lower than values from the middle or upper Palaeolithics. The metric cranial data analysed in FORDISC, characterize the skull as a male Vietnamese rather than a Chinese or White individual. Tooth morphology shows the sundadont pattern and tooth size corresponds to that of teeth from Bali, Java and Malayan Orang Asli. Remarkable are the marked asymmetries in the dentition with rotation of an upper premolar and congenital absence of a third molar. In these respects the CF skull is similar to dentitions belonging to the pygmoid villagers of Rampasasa, a village not far from the Liang Bua cave, and to LB1.

L’acromegalie est caracterisee par l’absence de freinage de l’hormone de croissance (growth hormone, GH) dans le test de l’hyperglycemie provoquee par voie orale. Un sous-groupe de patients acromegales presente non seulement un freinage insuffisant, mais aussi une augmentation paradoxale de la GH plasmatique suite a l’hyperglycemie, dont les mecanismes moleculaires ne sont pas connus. Par analogie avec le syndrome de Cushing dependant de l’alimentation, cette reponse paradoxale pourrait etre secondaire a l’expression illegitime du recepteur de GIP (glucose-dependent insulinotropic peptide, GIPR). Nous avons analyse l’expression de GIPR dans 41 echantillons d’adenomes somatotropes, dont 10 provenaient de patients avec une reponse paradoxale. Treize echantillons expriment des transcrits de GIPR (adenomes GIPR+), dont dix proviennent des patients avec une reponse paradoxale (100 %). Des mutations somatiques de GNAS1 sont trouvees dans 11 adenomes, exclusivement les GIPR−. La CGH-array montre une duplication du locus GIPR dans 5 adenomes GIPR+. Ce gain genomique est confirme par DNA-FISH, qui retrouve 3 a 4 copies de GIPR dans les noyaux des cellules somatotropes GIPR+. Le RNA-FISH, qui visualise l’ARN naissant dans les noyaux interphasiques, met en evidence l’expression de GIPR a partir d’un seul allele dans les adenomes GIPR+. L’exploration des mecanismes responsables de cette activation transcriptionnelle monoallelique de GIPR est en cours. En conclusion, l’expression illegitime du GIPR dans certains adenomes somatotropes explique le phenotype particulier des patients acromegales avec reponse paradoxale de GH a l’hyperglycemie. L’expression de GIPR pourrait representer un evenement moleculaire capable de promouvoir la tumorigenese dans les adenomes somatotropes non mutes pour GNAS1.

Macrophagic myofasciitis (MMF) is characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. Representative features of MMF-associated cognitive dysfunction (MACD) include (i) dysexecutive syndrome; (i) visual memory; (iii) left ear extinction at dichotic listening test. In present study we retrospectively evaluated the progression of MACD in 30 MMF patients. Most patients fulfilled criteria for non-amnestic/dysexecutive mild cognitive impairment, even if some cognitive deficits seemed unusually severe. MACD remained stable over time, although dysexecutive syndrome tended to worsen. Long-term follow-up of a subset of patients with 3 or 4 consecutive neuropsychological evaluations confirmed the stability of MACD with time, despite marked fluctuations.

Pairs of recombinant MVA (Modified Vaccinia Ankara) and FPV (Fowlpox Virus) expressing the same transgene are reasonable candidates for prime/boost regimens, because cross-reacting immune responses between the two vectors, both non-replicative in mammalian hosts, are very limited. The acceptor virus FPD-Red, a derivative of FPV, carrying a red fluorescent protein gene flanked by the homology regions of MVA deletion III, was constructed. The same MVA Transfer Plasmid Green, designed to insert transgenes into the MVA deletion III locus, can therefore be used to transfer transgenes into both acceptor viruses MVA-Red and FPD-Red with the described recently Red-to-Green gene swapping method. Cells infected by either recombinant virus can be sorted differentially by a simple and reliable FACS-based purification protocol. The procedure is carried out in primary chick embryo fibroblasts grown in serum-free media and was applied to the production of three rMVA/rFPV pairs expressing the H5N1 avian influenza antigens M1, M2 and NP. The viral genes were human codon-optimized and expressed at high levels in both chick and mammalian cells. Both single-step and multiple-step growth analyses showed no significant differences in growth due to the transgenes in either rMVA or rFPV derivatives.

BCL2-associated athanogene 1 (BAG1) is an anti-apoptotic factor that interacts with tau and regulates its proteasomal degradation. A significant increase of the BAG-1M isoform was found in Alzheimer's disease (AD) brains, and the protein co-localized with tau and amyloid. We carried out an association study of BAG1 in a population of 291 patients clinically diagnosed with frontotemporal lobar degeneration (FTLD), none of whom was a carrier of mutations in progranulin or microtubule associated protein tau genes and 374 with AD as compared with 314 age-and gender-matched controls. In addition, another candidate named Chromatin-modifying protein 5 (CHMP5) and located in the same linkage disequilibrium block, has been included in this study. The distribution of the two single nucleotide polymorphism (SNPs), rs844239 in CHMP5 and rs706118 in BAG1, covering 100% gene variability, were determined. A statistically significant decreased allelic frequency of the BAG-1 rs706118 SNP was observed in patients with FTLD as compared with controls (16.7 versus 23.9%; p = 0.007, OR: 0.35, CI: 0.25-0.50), whereas allelic frequency of the SNP in patients with AD was similar to controls (24.3%, p > 0.05). Conversely, no significant association was found as regards CHMP5 rs844239. Stratifying according to gender, no differences were observed. BAG-1 rs706118 SNP likely acts as protective factor for sporadic FTLD, but not for AD, suggesting its specific role in a pathogenic event in FTLD. Nevertheless, a replication study would be needed to confirm these preliminary results. © 2011 - IOS Press and the authors. All rights reserved.

Les adenomes corticotropes varient en taille, secretion, invasivite, sensibilite au traitement, et profil evolutif. Notre hypothese est que cette variabilite est liee a une variabilite moleculaire sous-jacente. Objectif Capturer de facon exhaustive la variabilite des anomalies chromosomiques dans les adenomes corticotropes. Methode Vingt-trois adenomes corticotropes operes a l’hopital Foch ont ete inclus. Les profils chromosomiques ont ete generes sur puce SNP (Illumina InfiniumCore-24v1-1 ; 300k SNPs). Les segments chromosomiques anormaux ont ete identifiees par le logiciel Genome Alteration Print (GAP), et filtres puis analyses par des programmes facon en R. Les donnees cliniques correspondantes ont ete colligees (sexe, âge, taille, invasion caverneuse, invasion sphenoidale, niveau de secretion et agressivite). Les comparaisons inter-groupes ont ete realisees avec le test de Wilcoxon pour les variables quantitatives et Fisher pour les variables qualitatives. Tous les patients ont signe un consentement, dans le cadre d’un projet valide par notre comite d’ethique. Resultats Globalement, on distingue deux groupes : – 8/23 tumeurs avec de multiples remaniement chromosomiques, notamment dans les chromosomes 3, 5, 7, 8, 9, 12 et 19 ; – 13/23 tumeurs avec peu ou pas d’anomalies chromosomiques. Ces profils d’anomalies chromosomiques ne sont pas associes au sexe (p = 1), a l’âge (p = 0,23), la taille (p = 0,9), invasion sphenoidale (p = 0,61), mais une tendance existe entre le profil chromosomique remanie et l’invasion caverneuse (p = 0,08), la secretion (p = 0,12) et l’agressivite (p = 0,11). Conclusion Il s’agit d’une des premieres etudes de la structure chromosomique des adenomes corticotropes. Ces anomalies chromosomiques semblent avoir un impact clinique qui reste a confirmer.

La physiopathologie des adenomes somatotropes est encore mal connue. Les anomalies cytogenetiques peuvent representer des mecanismes alternatifs de la tumorigenese dans les adenomes somatotropes non-mutes pour GNAS. Nous avons realise une analyse pangenomique haute resolution par CGH-array de 43 adenomes hypophysaires provenant de patients atteints de gigantisme ou d’acromegalie. Nous avons identifie deux groupes de tumeurs en fonction de leur instabilite genomique : les tumeurs a faible alteration du nombre de copies (

Ex vivo expansion of hematopoietic stem cells has been explored in the fields of stem cell biology, gene therapy and clinical transplantation. Recently, we demonstrated the existence of a circulating myogenic progenitor expressing the CD133 antigen. The relative inability of circulating CD133+ stem cells to reproduce themselves ex vivo imposes substantial limitations on their use for clinical applications in muscular dystrophies. Here we report that the use of cluster-assembled nanostructured titanium dioxide (ns-TiO 2 ) substrates, in combination with cytokine enriched medium, enables high-level expansion of circulating CD133+ stem cells in vitro. Furthermore, we demonstrate that expanded circulating CD133+ stem cells retain their in vitro capacity to differentiate into myogenic cells. The exploitation of cluster-assembled ns-TiO 2 substrates for the expansion of CD133+ stem cells in vitro could therefore make the clinical application of these stem cells for the treatment of muscle diseases practical.

2005Background: to characterize clinical, molecular and radiological features of diffuse gliomas with FGFR3-TACC3 fusions or FGFR1 mutations, which are both actionable with new oral anti-FGFR inhib...

Laboratory of Biological Anthropology, Department of Forensic Medicine, The Panum Institute,University of Copenhagen, 2200 Copenhagen, DenmarkKEY WORDS osteon population density (OPD); femur; histomorphometry; bone microscopyABSTRACT Unbiased selection of regions of inter-est (ROIs) and unbiased definition of histological struc-tures are needed to improve the repeatability of micro-scopic methods for age at death determination and toreduce operator subjectivity. We present resultsobtained by selecting ROIs according to stereologicalprinciples on a sample of 28 femoral cross sections ofCaucasoid males aged 20–89 years. A regular grid wasoverlaid on the cross section, and the ROIs wereselected as close as possible to the periosteum in theanterior, lateral, and medial regions. The areas consist-ing of all intact secondary osteons plus fragments wereoutlined and osteon population density, percent osteonpopulation, area, and perimeter were calculated usingstereological methods and software. Overall, the analy-ses of intra- and inter-section variability showed nosignificant difference between the ROIs, i.e., the loca-tion within the cross section of the ROIs does notaffect the outcome of the analyses. The individual vari-ability was found to be higher in adults aged 30–55years than in other age ranges. Am J Phys Anthropol000:000–000, 2010.

Advances in stem cell research have provided important understanding of the cell biology and offered great promise for developing new strategies for tissue regeneration. The beneficial effects of stem cell therapy depend also by the development of new approachs for the track of stem cells in living subjects over time after transplantation. Recent developments in the use of nanotechnologies have contributed to advance of the high-resolution in vivo imaging methods, including positron emission tomography (PET), single-photon emission tomography (SPECT), magnetic resonance (MR) imaging, and X-Ray computed microtomography (microCT). This review examines the use of nanotechnologies for stem cell tracking.

The aim of this study was to identify nonalcoholic fatty liver in obese children by magnetic resonance imaging (MRI) and to compare the findings with the data from ultrasonography and from clinical and laboratory testing.Sixty obese children, 6 to 14 years old, underwent hepatic MRI and abdominal ultrasonography. Biochemistry determinations included serum aminotransferases, lipid profile, glucose, and insulin. Anthropometry included body mass index, total and trunk fat, and fat-free mass obtained by dual-energy radiographic absorptiometry. Hepatic steatosis, judged as hepatic fat fraction by MRI, wasor=9%.By MRI, 14 (23%) children had hepatic steatosis; of those, 5 had a fat fraction of 9% to 18%, and 9 had a fat fraction18%. At univariate analysis, fat fraction was positively associated with being male, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase, body mass index z score, insulin, systolic pressure, and total and trunk fat mass. Hepatic steatosis was independently associated with alanine aminotransferase (P0.01). Overall, liver echogenicity on ultrasonography correlated well with fat fraction by MRI (correlation coefficient 0.527, P0.0001). Among the 27 children with increased liver echogenicity, 13 (48%) had hepatic fat fractionor=9%, and 89% of children with echogenicity graded 2 or 3 had fat fraction18%. All of the children (n = 9) with fat fraction18% had increased liver echogenicity, and in 8 of them it was graded 2 or 3, but the MRI fat fraction ranged greatly (28%-45%).In obese children, nonalcoholic hepatic steatosis may be associated with the metabolic syndrome. Ultrasonography may be valuable in identifying high hepatic fat accumulation, but its ability to identify lower fat accumulation in the liver is scanty compared with MRI.

Background and purpose: Progranulin (PGRN) expression is increased in activated microglia in Alzheimer's disease (AD) brain, suggesting a potential role in this pathology. Methods: A mutation scanning of exons and flanking regions of PGRN was carried out in 120 patients with sporadic frontotemporal lobar degeneration and 145 with sporadic AD. Results: Amongst variants not yet deposited, a novel allelic variant was identified in Exon 1 (g100169G > A). It leads to an amino acidic change (p.Gly35Arg) and was observed in a patient with late onset AD. In silico analysis predicted that this mutation is possibly damaging. A second variant (g.100165C > T), resulting in a silent mutation (pAsp33Asp), was found in a patient with semantic dementia and in another with early onset AD. Both variants were absent in 226 controls. In addition, two rare non-pathogenic variants lying very close to PGRN splice-site regions (IVS2 + 7G > A and IVS7 + 7G > A) were observed. Transcriptional analysis in peripheral blood mononuclear cells from patients demonstrated they do not affect exon splicing. Conclusions: A novel putative PGRN mutation leading to an amino acidic substitution was identified in a patient with clinical AD.

Cerebrospinal fluid (CSF) levels of interleukin (IL)-6, IL-11 and leukaemia inhibitory factor (LIF) were evaluated in 43 patients with Alzheimer's disease (AD) and 24 patients with frontotemporal lobar degeneration (FTLD) as compared with 30 agematched controls (CON), and correlated with clinical and demographic data and with CSF biomarkers amyloid beta (Aβ)42, total tau and tau phosphorylated at position 181 (P-tau). CSF IL-11 mean levels were significantly increased in AD and FTLD as compared with CON (6.5 ± 4.6 and 6.6 ± 5.1 versus 3.1 ± 3.3 pg/ml, P = 0.009). IL-6 mean levels did not differ between patients and CON (P > 0.05),whereas LIF levels were not detectable in patients or in CON. In AD patients, a significantly positive correlation between MMSE scores and IL-11 CSF concentration was observed (r = 0.344, P = 0.028). No correlations with CSF Aβ42, total tau and P-tau were found. IL-11, but not IL-6 levels are increased in AD and FTLD, and the highest peaks were observed in patients with a less severe degree of cognitive deterioration, therefore suggesting a role of this cytokine in early phases of neurodegeneration. © 2008 Steinkopff-Verlag.

Monocytes are known to play a key role in the initiation and progression of atherosclerosis and contribute to plaque destabilization through the generation of signals that promote inflammation and neoangiogenesis. In humans, studies investigating the features of circulating monocytes in advanced atherosclerotic lesions are lacking.Patients (mean age 69 years, 56% males) with intermediate asymptomatic carotid stenosis (40-70% in diameter) were evaluated for maximal stenosis in common carotid artery, carotid bulb and internal carotid artery, overall disease burden as estimated with total plaque area (TPA), greyscale and neovascularization in 244 advanced carotid plaques. Absolute counts of circulating CD14+ monocytes, of classical (CD14No correlation was found between monocytes and overall atherosclerotic burden, nor with high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). In contrast, plaque signs of neovascularization were associated with significantly lower counts of circulating CD14+ monocytes (297 versus 350 cells/mmNeovascularized atherosclerotic lesions selectively associate with lower blood levels of CD14+ and CD14

Marine borers such as the shipworm, Teredo navalis , can cause great destruction to wooden archaeological remains in the marine environment. The focus of this study was to investigate whether shipworm preferentially settle on one orientation of the wood over another, i.e. radial, tangential or transversal and if the resulting tunnels are oriented in a specific direction according to the fibres within the wood. This was investigated using Computed Tomography (CT) scanning and subsequent 3D modelling as a method of both quantifying the severity of attack by shipworm and examining the orientation of the tunnels. Panels of pine, cut in tangential, radial and transversal planes, were placed in the sea at a location where shipworm was known to be abundant. After attack, the panels were weighed, X-rayed, entrance holes counted and 3D CT models created. All results show a difference between the three planes. The specific direction of the single tunnels could be evaluated using the CT models, since the individual tunnels could be isolated, and followed throughout the panel. The results show that the radial plane suffered a more severe attack than either of the two other planes. These results have implications for archaeological interpretation and conservation. For example, the results show that ancient ships built with timbers cut in a radial plane (e.g. Viking Ships or other structural elements cut in radial plane) may be more prone to attack and thus require more protection than those built in tangential or transversal plane should they be raised (difficulties lifting due to fragility) or preserved in situ .

This paper addresses a specific type of intervention for health and wellbeing, i.e., brief interventions during nightlife events, aimed at improving partygoers' awareness of the risks related to the consumption of psychoactive substances. It is argued that a gamified modality would help overcome some limiting contextual constraints while preserving the seriousness of the intervention purpose. To support this last point, the paper describes two studies Ni?ź=i?ź227, Ni?ź=i?ź81 respectively. The first study was conducted in the field; it was found that after a game session, users' self-reported awareness of nightlife risks increased significantly from pre-session scores. In addition, users evaluated the intervention as credible in terms of its accuracy, novelty, and contextual appropriateness. The second study showed, under controlled laboratory conditions, that the number of correct answers about substance consumption consequences, substance characteristics, and risk prevention choices improved after the game session. Together, these studies suggest that using gamification as an attractor would not compromise the serious goals of this intervention modality.

Background and aims Monocytes are known to play a key role in the initiation and progression of atherosclerosis and contribute to plaque destabilization through the generation of signals that promote inflammation and neoangiogenesis. In humans, studies investigating the features of circulating monocytes in advanced atherosclerotic lesions are lacking. Methods Patients (mean age 69 years, 56% males) with intermediate asymptomatic carotid stenosis (40–70% in diameter) were evaluated for maximal stenosis in common carotid artery, carotid bulb and internal carotid artery, overall disease burden as estimated with total plaque area (TPA), greyscale and neovascularization in 244 advanced carotid plaques. Absolute counts of circulating CD14+ monocytes, of classical (CD14 high CD16−), intermediate (CD14 high CD16+) and non-classical (CD14 low CD16+) monocytes and HLA-DR+ median fluorescence intensity for each subset were evaluated with flow cytometry. Results No correlation was found between monocytes and overall atherosclerotic burden, nor with high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). In contrast, plaque signs of neovascularization were associated with significantly lower counts of circulating CD14+ monocytes (297 versus 350 cells/mm 3 , p = 0.039) and of classical monocytes (255 versus 310 cells/mm 3 , p = 0.029). Conclusions Neovascularized atherosclerotic lesions selectively associate with lower blood levels of CD14+ and CD14 high CD16− monocytes independently of systemic inflammatory activity, as indicated by normal hsCRP levels. Whether the reduction of circulating CD14+ and CD14 high CD16− monocytes is due to a potential redistribution of these cell types into active lesions remains to be explored.

In this study we focused on determining the transcriptome differences between Waldenström's Macroglobulinemia (WM) and IgM Monoclonal Gammopathy of Undetermined Significance (IgM-MGUS) by gene expression profiling (GEP) considering all the different transcript isoforms of genes that map the human transcriptome (coding transcripts, non-coding transcripts). We performed the analysis on BM B cell clones (CD45+,CD38+,CD19+,LAIR-1-,CD27dim,IgM+,CD22dim,CD25+) from WM (n=21) and IgM-MGUS (n=13) patients. These populations were identified with an 8-colors panel by flow cytometry and successively isolated by cell sorting. GEP of WM vs. IgM-MGUS BM B cell clones was performed using Affymetrix Gene Chip HTA 2.0. Data was first pre-processed using Affymetrix Expression Console and then normalized using ComBat (Johnson et. al. Biostatistics2007) and quantile normalization. We investigated both differential expression using SAM test (Tusher et. al. Proc Natl Acad Sci USA2001) and differential variability using F-test to compare means and variances between groups, respectively. In particular, testing the variability is useful to investigate a heterogeneous disease like Waldenström's Macroglobulinemia as well as IgM-MGUS, since B clonal cells proliferation and growth are driven by different mutations acting as perturbations in different molecular pathways, and these perturbations vary from individual to individual. False Discovery Rate (FDR) p-values adjusted for multiple testing below 5% were considered significant (Storey J R Stat Soc 2002). "Genomic Regions Enrichment of Annotations Tool" (GREAT) (McLean t. al. Nat Biotechnol 2010) was used to annotate the selected probe sets and perform biological pathway enrichment analysis. We considered 67,529 probe sets for the analyses. There were no differentially expressed probe sets in means after the correction for multiple comparisons, whereas 446 probe sets showed differential variability between IgM-MGUS and WM samples. Figure 1 shows how the selected probe sets map on the human genome according to GREAT. Enrichment analysis performed on these 446 probe sets showed after correction for multiple testing (FDR threshold set at 5%), significant enrichment for apoptosis, B cell receptor signaling pathway, chemokine-signaling pathway, ERBB signaling pathway, PI3K-AKT signaling pathway and WNT signaling pathway. Of note, BCL2, RAF1, MAPK1, GRB2, GSK3B, NRG1, SOS1, WNT5A, NLK, PTK2B genes belonging to these pathways, demonstrated significant different expression variability. We found that IgM-MGUS showed significantly increased variability of expression of all the selected genes (a part from SOS1 and NLK) across patients. We could speculate that IgM-MGUS B cell clones showed increased expression variability in the identified genes in their developmental stage, indicating the likely presence of cells at different step of differentiation whereas the expression of the same genes was more stable in WM patients. In summary, we found that IgM-MGUS was characterized by higher variability in gene expression across patients, which could be related to higher intra-patient variability suggesting the possible link between expression variability and genetic heterogeneity. Important functions showing increased variability in IgM-MGUS compared to WM were related to apoptosis, B cell receptor signaling pathway, chemokine-signaling pathway, ERBB signaling pathway, PI3K-AKT signaling pathway and WNT signaling pathway. Larger datasets and clinical evolution of IgM-MGUS individuals would provide a deeper insight into the functional context of the pathways and the differential variable genes highlighted by the comparison between IgM-MGUS and WM. Figure 1 Distribution of the 446 probes showing significant differential variability in IgM-MGUS vs. WM samples. Figure 1. Distribution of the 446 probes showing significant differential variability in IgM-MGUS vs. WM samples. Disclosures No relevant conflicts of interest to declare.

Neuroendocrine carcinomas are rare tumors. In the head and neck region they are most common in the larynx, where they represent 0.5-1% of epithelial cancers. Diagnosis requires the recognition of the typical neuroendocrine architecture and morphology and the immunohistochemical confirmation of neuroendocrine differentiation. In the 1991 WHO classification laryngeal neuroendocrine carcinomas have been divided into carcinoids, atypical carcinoids, small cell carcinomas and paragangliomas. Atypical carcinoids in the head and neck region usually show an aggressive behavior analogous to poorly differentiated carcinomas, and are resistant to chemo- and radiotherapy. For this reason, it was recently proposed to change their designation to “moderately differentiated neuroendocrine carcinomas”. We present the clinical and histopathological features of 2 moderately differentiated neuroendocrine carcinomas of the larynx, one large cell poorly differentiated neuroendocrine carcinoma of the oropharynx, and one small cell carcinoma of the minor salivary glands of the tongue. The patient with small cell carcinoma was free from disease 26 months after radical surgery, while the other patients showed liver, lung and bone metastases 18, 26 and 24 months after the diagnosis despite radical surgery or concomitant intra-arterial chemotherapy and radiotherapy.

Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is caused by mutations in the dystrophin gene, leading to absence of muscular dystrophin and to progressive degeneration of skeletal muscle. We have demonstrated that the exon skipping method safely and efficiently brings to the expression of a functional dystrophin in dystrophic CD133+ cells injected scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the best preclinical model of Duchenne muscular dystrophy, mimicking the human pathology in genotypic and phenotypic aspects. Here, we assess the capacity of intra-arterial delivered autologous engineered canine CD133+ cells of restoring dystrophin expression in Golden Retriever muscular dystrophy. This is the first demonstration of five-year follow up study, showing initial clinical amelioration followed by stabilization in mild and severe affected Golden Retriever muscular dystrophy dogs. The occurrence of T-cell response in three Golden Retriever muscular dystrophy dogs, consistent with a memory response boosted by the exon skipped-dystrophin protein, suggests an adaptive immune response against dystrophin.

The effectiveness of the so-called skeletal markers of activity as functional indicators is widely debated. Among them, certain morphological features of the anterior aspect of the femoral head-neck junction (Poirier’s facet, cervical fossa of Allen, etc.) have been considered in relation to some behaviors and specific activities (e.g., squatting, horseback riding, etc.). However, disagreement on terminology and descriptions, the absence of standardized scoring methods and poor knowledge of the variability and distribution of these features make it difficult to interpret their meaning. The aim of this study is to analyze the variability of the anterior aspect of the femoral neck through a new scoring method taking into account three main traits: Poirier’s facet, plaque, and cribra (including the Allen’s fossa). This method has been applied to a sample of 225 adult individuals of both sexes coming from an identified modern skeletal collection, achieving low intraobserver and interobserver error values. The results highlight some significant trends: plaque, almost always bilateral, appears to be a normal condition of the femur, being present in approximately 90% of the individuals. Cribra is more frequent in females and decreases with age. Poirier’s facet shows a very low frequency. This method allows the representation of both the anatomical diversity of the region already described in literature and part of the variability never considered before. Our results suggest caution in considering these features as markers related to specific activities.

There are very few tarpons (family Megalopidae) and other elopiforms (fam. Elopidae) recorded in the Tertiary. The records are mainly from the Eocene, and more abundant in the ‘North Sea Region’ in Early Eocene, as for instance the large Danish forms. They are also found in late Early Eocene in London Clay, in Late Eocene in Caucasia, and in Miocene of SE-Asia, although none were described from the famous Bolca fauna (early Mid Eocene). However, there is a large, still undescribed ‘tarpon-like’ fish in the Bolca Museum (obs. MECL & NB 2014). There are even fewer described from the long Cretaceous period, 4-5? genera, including the large Paraelops from Romualdo Formation, Araripe Basin, NE-Brazil, and a large undescribed megalopid from Tlayua, Pueblo, Mexico, both ‘Mid Cretaceous’. The oldest elopiforms are from Late Jurassic Solnhofen Limestone. The large Danish ‘tarpons’ come from ‘cementstones’ in Fur Formation (earliest Eocene, ca. 55 m.y.), and here we report an almost complete specimen which is ca. 110 cm long; however, big isolated scales found in this formation indicate fishes at least twice as big (comparable in size with the living Tarpon atlanticus - over 2½ m). This specimen has a heavy skull lacking the lower jaw, and is preserved in 3-D. It was split in the midline and acid prepared, being then CT-scanned in Aarhus and reconstructed in the Laboratory of Biological Anthropology, Copenhagen University to attempt precise, detailed comparisons with modern skulls and with the 3-D skulls preserved in concretions from the London Clay.

X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

International audience; Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the geneGPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.

Contexte Le syndrome de Nelson associe classiquement un macroadenome corticotrope et une ACTH elevee apres surrenalectomie bilaterale. En 2007, le concept de progression tumorale corticotrope etait propose comme plus adapte a la pratique clinique moderne. Comme les progressions rapides sont bien plus problematiques que les progressions lentes, nous proposons d’affiner ce concept en considerant la vitesse de progression tumorale corticotrope (VPC). Objectif Decrire la VPC et identifier les facteurs associes. Methodes Quatre-vingt-dix-neuf patients avec maladie de Cushing suivis a Cochin, ayant subi une surrenalectomie entre 1991 et 2016 sont inclus. Les donnees cliniques et biologiques (tests au ddAVP, au CRH, au freinage fort) ont ete colligees, ainsi que l’histologie hypophysaire. Les IRM hypophysaires ont ete relues. La VPC a ete mesuree, exprimee en mm/an. Le suivi moyen etait de 8 ans. Resultats La VPC maximale par patient varie entre 0 et 40,7 mm/an. La VPC maximale est observee entre 0,13 et 14,4 annees apres surrenalectomie. La VPC maximale est correlee a l’ACTH dans l’annee suivant la SBT (p = 0,02). Pendant le suivi, la VPC est correlee au pic d’ACTH apres ddAVP (p = 0,003). L’apoplexie, le syndrome caverneux et les troubles du champ visuel sont associees aux VPC les plus elevees (p Discussion La VPC est probablement la mesure la plus adaptee pour le suivi des adenomes corticotropes apres surrenalectomie.

With a view toward reduction of graft loss, we explored pancreatic islet transplantation within fibrin matrices rendered pro-angiogenic by incorporation of minimal doses of vascular endothelial growth factor-A165 and platelet-derived growth factor-BB presented complexed to a fibrin-bound integrin-binding fibronectin domain. Engineered matrices allowed for extended release of pro-angiogenic factors and for their synergistic signaling with extracellular matrix-binding domains in the post-transplant period. Aprotinin addition delayed matrix degradation and prolonged pro-angiogenic factor availability within the graft. Both subcutaneous (SC) and epididymal fat pad (EFP) sites were evaluated. We show that in the SC site, diabetes reversal in mice transplanted with 1,000 IEQ of syngeneic islets was not observed for islets transplanted alone, while engineered matrices resulted in a diabetes median reversal time (MDRT) of 38 days. In the EFP site, the MDRT with 250 IEQ of syngeneic islets within the engineered matrices was 24 days versus 86 days for islets transplanted alone. Improved function of engineered grafts was associated with enhanced and earlier (by day 7) angiogenesis. Our findings show that by engineering the transplant site to promote prompt re-vascularization, engraftment and long-term function of islet grafts can be improved in relevant extrahepatic sites.

Several micro(mi)RNA are deregulated in brain, cerebrospinal fluid (CSF), and serum/plasma from patients with Alzheimer's disease (AD). The aim of the study was to profile circulating miRNAs in serum as non-invasive biomarkers for AD, correlating them with those identified in CSF, the biological fluid which better reflects biochemical changes occurring during pathological processes in the brain and may provide a robust indicator of AD-related disease pathogenesis thanks to the evidence of low amyloid and high levels of tau and hyperphosphorylated tau. Using a two-step analysis (array and validation through real-time PCR), a down-regulation (mean fold change ± SEM) of miR-125b (0.415 ± 0.11 versus 1.381 ± 0.36, p = 0.009), miR-23a (0.111 ± 0.03 versus 0.732 ± 0.14, p < 0.001), and miR-26b (0.414 ± 0.11 versus 1.353 ± 0.39, p < 0.01), out of 84 tested, was shown in serum from 22 AD patients compared with 18 non-inflammatory and 8 inflammatory neurological controls (NINDCs and INDCs) and 10 patients with frontotemporal dementia. Significant down-regulation of miR-125b and miR-26b was also confirmed in CSF from AD patients versus NINDCs (miR-125b: 0.089 ± 0.03 versus 0.230 ± 0.08, p < 0.001; miR-26b: 0.217 ± 0.06 versus 1.255 ± 0.29, p < 0.001, mean fold change ± SEM, respectively), whereas data were not replicated for miR-23a. In serum, miR-125b had an AUC of 0.82 to distinguish AD from NINDCs (95% CI: 0.65-0.98, p = 0.005). In conclusion, we demonstrated that cell-free miR-125b serum levels are decreased in serum from patients with AD as compared with NINDC and distinguish between AD and NINDCs with an accuracy of 82%. Supplementary Figure 1. A) Array miRNA list; B) Heat map. Data are expressed as fold change (fold difference) in Alzheimer's disease patients versus controls and normalized on cel-miR-39. Each square represents a single miRNA. Green indicates down-regulation and red indicates upregulation.

The age of an individual is often a fundamental piece of data in connection with forensic identification of unidentified bodies. The methods most often used are based on visu - ally determining various morphological, age-related changes in the skeleton (or teeth, although odontological methods are not reviewed in this paper). As such, these methods are all relative: ie, they do not obtain results in calendar years but estimates of the age at death, often with a rather large range. Recently, methods have been proposed for more direct ascertainment of age at death: eg, protein racemization and radiocarbon methods. The latter method, especially, may yield absolute age (year of birth), because radiocarbon activity (as measured in specific proteins in specific cells or tissues of the body) may be in equilibrium with the so-called bomb-pulse, when atmospheric radiocarbon content has changed markedly from one year to another. This review covers the basic and most often used gross morphological methods, radiologically-based methods, biochemical methods, and radiocarbon dating.

A hexanucleotide repeat expansions in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis and/or frontotemporal lobar degeneration. The same mutation has been described in a patient with bipolar disorder, but up to now, not in patients suffering from schizophrenia. We determined the frequency of the C9ORF72 hexanucleotide repeat expansions in a population of 298 patients with schizophrenia or schizoaffective disorder. The pathogenic repeat expansion was detected in 2 patients (0.67%). Both of them presented with auditory hallucinations and had comorbid alcohol abuse. In addition, a positive family history for psychiatric and/or neurodegenerative diseases was present. The repeat expansion in the C9ORF72 gene is a rare, but possible, cause of schizophrenic spectrum disorders. We cannot rule out however whether the number of repeats influence the phenotype. © 2014 Elsevier Inc.

International audience

Objective Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. Methods In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. Results The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33–0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p

Emerging evidence underlines the importance of micro(mi)RNAs in the pathogenesis of multiple sclerosis (MS). Free-circulating miRNAs were investigated in serum from MS patients compared to controls. Statistically significant decreased levels of miR-15b, miR-23a and miR-223 were observed in MS patients ( p < 0.05). Results were validated and replicated in two further independent MS populations. A direct correlation between miRNA levels and the EDSS score was determined in PPMS ( p < 0.007). The generalized trend toward miRNA down-regulation could result in over-expression of target genes involved in disease pathogenesis. Circulating miRNA profiling could thus represent a new avenue to identify easily detectable disease biomarkers.

Recent studies have reported that quantifying symphyseal and auricular surface curvature changes on 3D models acquired by laser scanners has a potential for age estimation. However, no tests have been carried out to evaluate the repeatability of the results between different laser scanners. 3D models of the two pelvic joints were generated using three laser scanners (Custom, Faro, and Minolta). The surface curvature, the surface area, and the distance between co-registered meshes were investigated. Close results were found for surface areas (differences between 0.3% and 2.4%) and for distance deviations (average

Perianal disease (PAD) sometimes complicates true ulcerative colitis (UC) with an incidence approaching 5 %. Although its pathogenesis is unknown and probably multifactorial, reassessment of clinical, endoscopic, histological, and imaging findings is always recommended to exclude a misdiagnosed Crohn’s disease (CD). Moreover, PAD may occur in UC patients who undergo colectomy with ileal pouch-anal anastomosis (IPAA). Pouch fistulas can be classified into pouch CD-related fistulas, arising in a setting of de novo CD of the pouch, or nonpouch CD-related fistulas, usually representing the later presentation of an initial anastomotic leak. PAD may involve the genital region, mostly in female patients with a 4–12 % incidence rate of ileal pouch-vaginal fistulas. Imaging of the perianal compartment is crucial for prompt and accurate diagnostic assessment of PAD in UC patients, especially for potential candidates for surgery, both in the preoperative and postoperative settings. Magnetic resonance imaging (MRI) is considered the gold standard technique in the assessment and follow-up of PAD, whereas computed tomography (CT) plays a major role in emergency conditions. Transanal and transperineal ultrasound represent low cost and accurate imaging modalities currently used in clinical practice.

Approximately 15 % of patients with ulcerative colitis experience at least one bout of acute severe colitis during their lifelong course. Diagnosed according to clinical criteria, acute severe colitis represents a serious condition that needs intensive in-hospital treatment and may lead to perform urgent colectomy if unresponsive. Currently rather uncommon, toxic megacolon is the end of the spectrum of acute severe colitis. Plain abdominal radiographs may prove useful to assess the presence and entity of colonic dilatation and the gross disease distribution. Urgent multidetector CT is increasingly used to assess patients with acute severe colitis, as it allows assessment of colonic mural thickening, stratification, dilatation, longitudinal disease extent and perivisceral changes. In selected patients water enema multidetector CT with limited or no bowel preparation may be useful to further improve assessment of acute ulcerative colitis changes, severity and extent. Furthermore, acute manifestations of ulcerative colitis may occasionally correspond to bowel perforation or to infectious superimposition with Clostridium difficile or Cytomegalovirus colitis.

Background To assess the accuracy of transperineal ultrasound (TPUS), in comparison with magnetic resonance imaging (MRI), in classifying perianal Crohn's disease (CD) according to Parks' classification and the American Gastroenterological Association criteria. Methods Fifty-nine consecutive patients with confirmed or suspected perianal CD underwent TPUS and MRI within 10 days. An independent expert surgical evaluation, which took into account proctological and MRI findings, was used as the gold standard. Fistulae and perianal disease were classified according to Parks' classification and American Gastroenterological Association criteria, respectively. Results Forty-six patients showed 64 fistulae (9 intersphincteric, 34 transsphincteric, 2 suprasphincteric, 9 extrasphincteric, and 10 anovaginal) and 23 abscesses were also found. Fifty-one of 54 perianal fistulae (per-lesion sensitivity: 94.4%) and 9 of 10 anovaginal fistulae (sensitivity: 90.0%) were detected and 58 were correctly classified by TPUS (sensitivity: 90.6%; positive predictive value: 93.4%). Overall, TPUS correctly detected and classified the fistulae in 89% of patients and the agreement for classifying perianal fistulae between TPUS and MRI was excellent (K value: 0.783). In contrast, 11 of 23 abscesses were correctly diagnosed by TPUS (sensitivity: 47.8%); although 14 abscesses were diagnosed by TPUS, only 11 were confirmed by MRI (positive predictive value: 78.6%). Overall, TPUS correctly detected and classified fistulae and associated abscesses in 67.3% of patients. Agreement between MRI and TPUS in discriminating simple (15) and complex (29) perianal disease was fairly good (K value: 0.57). Conclusions TPUS is a simple and accurate diagnostic method for classifying perianal fistulae in CD and could be used for the preliminary assessment and follow-up of perianal CD.

In the aging human immunodeficiency virus (HIV)-infected population with improved immune function under antiretroviral treatment, many different opportunistic disorders may be encountered, along with rare presentations or complicated forms of common diseases. Renal and urologic abnormalities observed in the setting of HIV infection or acquired immunodeficiency syndrome are reviewed with their imaging appearances, including renal dysfunction, urolithiasis, urinary tract infections and related complications, genitourinary tuberculosis, vascular lesions, urogenital tumors, and bladder abnormalities, with emphasis on characterization. In HIV-positive patients, early cross-sectional imaging is warranted to detect uncommon disorders and complications, with the aim to preserve renal function.

A hexanucleotide repeat expansion in the chromosome 9 Open Reading Frame 72 gene (C9ORF72) has recently been reported to be cause of familial amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Nevertheless, in the last few years this mutation has been found to be associated with heterogeneous phenotypes, including multiple sclerosis (MS) in concurrence with amyotrophic lateral sclerosis. In this study, we sought to evaluate the presence of the C9ORF72 repeat expansion in a cohort consisting of 314 patients with MS and 222 control subjects. No pathogenic expansion was found in MS and control populations, suggesting that C9ORF72 does not play a major role in MS pathogenesis. © 2014 Elsevier Inc.

The effectiveness of the so-called skeletal markers of activity as functional indicators is widely debated. Among them, certain morphological features of the anterior aspect of the femoral head-neck junction (Poirier's facet, cervical fossa of Allen, etc.) have been considered in relation to some behaviors and specific activities (e.g., squatting, horseback riding, etc.). However, disagreement on terminology and descriptions, the absence of standardized scoring methods and poor knowledge of the variability and distribution of these features make it difficult to interpret their meaning. The aim of this study is to analyze the variability of the anterior aspect of the femoral neck through a new scoring method taking into account three main traits: Poirier's facet, plaque, and cribra (including the Allen's fossa). This method has been applied to a sample of 225 adult individuals of both sexes coming from an identified modern skeletal collection, achieving low intraobserver and interobserver error values. The results highlight some significant trends: plaque, almost always bilateral, appears to be a normal condition of the femur, being present in approximately 90% of the individuals. Cribra is more frequent in females and decreases with age. Poirier's facet shows a very low frequency. This method allows the representation of both the anatomical diversity of the region already described in literature and part of the variability never considered before. Our results suggest caution in considering these features as markers related to specific activities.

Nightlife well-being interventions, although much needed, face several challenges related to the specificity of the context addressed. We argue that a game-facilitated intervention helps with facing these challenges. The characteristics of a game developed to this goal and the results of user tests conducted in situ are presented.

Micro-CT offers high spatial resolution of the distribution of stem cells and provides rapid reconstruction of 3D images and quantitative volumetric analysis. Together with real-time PCR analysis, micro-CT offers the possibility to obtain a quantification of the number of cells that are able to migrate from the bloodstream inside the muscular tissues. Here, we studied for the first time the kinetics of the human cells injected into the femoral artery of DMD animal model. It is fundamental to determine whether the cells disseminate and entrap only within the capillary system of downstream muscles and/or they are able to reach the non-injected muscles and other organs through blood flow. The efficient transplantation of stem cells to dystrophic-deficient muscle reinforced the utility of intra-arterial delivery of cells as a viable approach for cell-based clinical therapies of neuromuscular diseases.

Loss of skeletal muscle tissue caused by traumatic injury or damage due to myopathies produces a deficit of muscle function for which there is still no clinical treatment. Transplantation of myogenic cells, themselves or combined with materials, has been proposed to increase the regenerative capacity of skeletal muscle but it is hampered by many limitations, such as low cell survival and engraftment or immunological reaction and low biocompatibility of the exogenous materials. Recently, myoblast sheet engineering, obtained with thermoresponsive culture dishes, has attracted attention as a new technique for muscle damage treatment. For this purpose, a series of thermoresponsive hydrogels, constituted by poly(N-isopropylacrylamide-co-2-hydroxyethylmethacrylate) [p(NIPAAM-co-HEMA)] were synthesized by a simple and inexpensive free-radical polymerization of the two co-monomers with a redox initiator. Different ratios of N-isopropylacrylamide (NIPAAm) and 2-hydroxyethylmethacrylate (HEMA) have been examined to evaluate the effects on physicochemical, mechanical and optical hydrogel properties. The murine muscle cell line C

Objectives As forensic age estimations in the living are performed without medical indication, there is a need for the development of non-ionizing methods. This study investigates the use of 1.0 T MRI to visualize the ossification status of the medial end of the clavicle. Material and methods T2 weighted 3D images were collected from a 1.0 T MR system. We prospectively scanned 102 subjects, 47 autopsy cases and 55 living volunteers (12–33 years). Images were scored in blind trials by three observers using a 4-stage system. Observers differed by level of training and radiological expertise. Results Motion artefacts reduced image resolution in living subjects. However, mean age at stage 4 was significantly different from mean age at stage 2 and 3. The minimum age at stage 4 was 19.8 years. Inter-observer agreement was moderate for autopsy cases and slight for living subjects. By contrasting subjects of “incomplete fusion” (≤ stage 3 on both sides) against “fused” (at least one stage 4), agreement rate rose to moderate ( K = 0.414) for living subjects. Despite the low agreement rate, no subject younger than 18 years was assessed as having “fused” clavicles. Conclusion At lower image resolution, a 2-stage system increases agreements rates among observers. To further increase accuracy, clavicle staging needs to be performed by trained observers. If available, a 1.0 T MR system may be used for age estimation in the living. However, further studies are needed to ensure that the ability to discriminate adults from minors, i.e. 18 years, is maintained.