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Mesonephric carcinoma is a rare form of gynecologic cancer derived from mesonephric remnants usually located in the lateral wall of the uterine cervix. An analogous tumor occurs in the adnexa, female adnexal tumor of probable Wolffian origin. The pathogenesis and molecular events in mesonephric carcinoma are not known. The aim of this study was to examine the molecular alterations in mesonephric carcinoma to identify driver mutations and therapeutically targetable mutations. This study consisted of 19 tumors from 17 patients: 18 mesonephric carcinomas (15 primary tumors and three metastatic tumors) and 1 female adnexal tumor of probable Wolffian origin. In two patients, both primary and metastatic tumors were available. Genomic DNA was isolated and targeted next-generation sequencing was performed to detect mutations, copy number variations, and structural variants by surveying full exonic regions of 300 cancer genes and 113 selected intronic regions across 35 genes. Fluorescence in situhybridization (FISH) for 1p and 1q was performed in two cases. Eighty-one percent (13/16) of mesonephric carcinomas had either a KRAS(n=12) or NRAS(n=1) mutation. Mutations in chromatin remodeling genes (ARID1A, ARID1B, or SMARCA4) were present in 62% of mesonephric carcinomas. All mesonephric carcinomas lacked mutations in PIK3CAand PTEN. The most common copy number alteration was 1q gain, found in 12 (75%) mesonephric carcinomas; this was confirmed by FISH in two cases. Mesonephric carcinoma is characterized by molecular alterations that differ from those of more common variants of cervical and endometrial adenocarcinoma, which harbor KRAS/NRASmutations in 7% and 25% of cases, respectively. KRAS/NRASmutations are common in mesonephric carcinoma and are often accompanied by gain of 1q and mutations in chromatin remodeling genes. Targeting inhibitors of the RAS/MAPK pathway may be useful in the treatment of mesonephric carcinoma.

Mesonephric carcinoma is a rare form of gynecologic cancer derived from mesonephric remnants usually located in the lateral wall of the uterine cervix. An analogous tumor occurs in the adnexa, female adnexal tumor of probable Wolffian origin. The pathogenesis and molecular events in mesonephric carcinoma are not known. The aim of this study was to examine the molecular alterations in mesonephric carcinoma to identify driver mutations and therapeutically targetable mutations. This study consisted of 19 tumors from 17 patients: 18 mesonephric carcinomas (15 primary tumors and three metastatic tumors) and 1 female adnexal tumor of probable Wolffian origin. In two patients, both primary and metastatic tumors were available. Genomic DNA was isolated and targeted next-generation sequencing was performed to detect mutations, copy number variations, and structural variants by surveying full exonic regions of 300 cancer genes and 113 selected intronic regions across 35 genes. Fluorescence in situ hybridization (FISH) for 1p and 1q was performed in two cases. Eighty-one percent (13/16) of mesonephric carcinomas had either a KRAS (n=12) or NRAS (n=1) mutation. Mutations in chromatin remodeling genes (ARID1A, ARID1B, or SMARCA4) were present in 62% of mesonephric carcinomas. All mesonephric carcinomas lacked mutations in PIK3CA and PTEN. The most common copy number alteration was 1q gain, found in 12 (75%) mesonephric carcinomas; this was confirmed by FISH in two cases. Mesonephric carcinoma is characterized by molecular alterations that differ from those of more common variants of cervical and endometrial adenocarcinoma, which harbor KRAS/NRAS mutations in 7% and 25% of cases, respectively. KRAS/NRAS mutations are common in mesonephric carcinoma and are often accompanied by gain of 1q and mutations in chromatin remodeling genes. Targeting inhibitors of the RAS/MAPK pathway may be useful in the treatment of mesonephric carcinoma.

The problems of distracted driving and distracted pedestrian accidents have attracted the attention of public health officials, transportation and psychology researchers, and communication scholars. Though public safety campaigns intended to curb dangerous texting behaviors have been implemented, relatively little is known about the psychological processes involved in these behaviors. Our study integrates emerging research on automatic behavior, self-control, and mindfulness in an attempt to explain why many individuals believe that such behavior is dangerous but engage in it anyway. Our survey study (N= 925) of college students (n= 313) and adults (n= 612) revealed that texting automaticity, trait self-control, and the “acting with awareness” facet of trait mindfulness were all uniquely predictive of texting while driving as well as texting while walking. Further, we observe that texting automaticity is more strongly related to the frequency of texting while walking than driving. Together, the findings synthesize disparate strands of research on cognition and media use and demonstrate the importance of distinguishing among types of consciousness to understanding mobile communication behavior.

The aim of this study is to evaluate the influence of SFRC repairs of different thicknesses on the mechanical performance of RC slabs, especially with respect to the crack pattern and level of cracking load. To understand the influence of SFRC, in terms of performance and variation of cracking load after repairing, a comparison with a reinforced concrete slab without fiber reinforcement was made. The study shows also the mechanical characterization of SFRC through conventional testing, to evaluate compressive strength, fracture energy, tensile strength and toughness. Concerning the application of SFRC on the concrete slab surface, the bond was improved by removing a small amount of superficial material. Finally, the experimental results on cracks distribution, displacements and level of cracking load are shown.

Current treatments that use hematopoietic progenitor cell (HPC) transplantation in acute myeloid leukemia (AML) patients substantially reduce the risk of relapse, but are limited by the availability of immune compatible healthy HPCs. Although cellular reprogramming has the potential to provide a novel autologous source of HPCs for transplantation, the applicability of this technology toward the derivation of healthy autologous hematopoietic cells devoid of patient‐specific leukemic aberrations from AML patients must first be evaluated. Here, we report the generation of human AML patient‐specific hematopoietic progenitors that are capable of normal in vitro differentiation to myeloid lineages and are devoid of leukemia‐associated aberration found in matched patient bone marrow. Skin fibroblasts were obtained from AML patients whose leukemic cells possessed a distinct, leukemia‐associated aberration, and used to create AML patient‐specific induced pluripotent stem cells (iPSCs). Through hematopoietic differentiation of AML patient iPSCs, coupled with cytogenetic interrogation, we reveal that AML patient‐specific HPCs possess normal progenitor capacity and are devoid of leukemia‐associated mutations. Importantly, in rare patient skin samples that give rise to mosaic fibroblast cultures that continue to carry leukemia‐associated mutations; healthy hematopoietic progenitors can also be generated via reprogramming selection. Our findings provide the proof of principle that cellular reprogramming can be applied on a personalized basis to generate healthy HPCs from AML patients, and should further motivate advances toward creating transplantable hematopoietic stem cells for autologous AML therapy. StemCells2013;33:1839–1849

Inflammatory myofibroblastic tumor is a distinctive, rarely metastasizing mesenchymal neoplasm composed of fascicles of spindle cells with a prominent inflammatory infiltrate. Roughly 50% of inflammatory myofibroblastic tumors harbor ALK receptor tyrosine kinase gene rearrangements. Such tumors are usually positive for ALK by immunohistochemistry. The molecular pathogenesis of ALK-negative inflammatory myofibroblastic tumors is largely unknown. A recent study identified rearrangements of ROS1 (another tyrosine kinase receptor) in a subset of ALK-negative inflammatory myofibroblastic tumors. Immunohistochemistry for ROS1 has been shown to correlate with ROS1 rearrangement in lung adenocarcinomas. The purpose of this study was to determine whether immunohistochemistry for ROS1 could predict ROS1 rearrangement in inflammatory myofibroblastic tumor. In total, 30 inflammatory myofibroblastic tumors were evaluated, including 21 ALK-positive tumors (10 confirmed to harbor ALK rearrangements, with TPM3, CLTC, RANPB2, and FN1 fusion partners) and 9 ALK-negative tumors (including 2 known to harbor ROS1 rearrangements). Immunohistochemistry was performed on whole tissue sections following pressure cooker antigen retrieval using a rabbit anti-ROS1 monoclonal antibody. The results were scored as ‘positive’ or ‘negative,’ and the pattern of staining was recorded. Three ALK-negative inflammatory myofibroblastic tumors (including both tumors with known ROS1 rearrangements) showed immunoreactivity for ROS1, whereas all ALK-positive inflammatory myofibroblastic tumors were negative for ROS1. One ROS1-positive inflammatory myofibroblastic tumor (with YWHAE-ROS1 fusion) showed strong, diffuse cytoplasmic and nuclear staining; one case (with TFG-ROS1 fusion) showed weak, diffuse and dot-like cytoplasmic staining; and one case (fusion partner unknown) showed moderate, diffuse and dot-like cytoplasmic staining. Expression of ROS1 correlates with ROS1 gene rearrangement in inflammatory myofibroblastic tumor. These findings suggest that immunohistochemistry for ROS1 may be useful to support the diagnosis of a subset of inflammatory myofibroblastic tumors and may select some clinically aggressive cases for targeted therapy directed against ROS1.

Inflammatory myofibroblastic tumor is a distinctive, rarely metastasizing mesenchymal neoplasm composed of fascicles of spindle cells with a prominent inflammatory infiltrate. Roughly 50% of inflammatory myofibroblastic tumors harbor ALKreceptor tyrosine kinase gene rearrangements. Such tumors are usually positive for ALK by immunohistochemistry. The molecular pathogenesis of ALK-negative inflammatory myofibroblastic tumors is largely unknown. A recent study identified rearrangements of ROS1(another tyrosine kinase receptor) in a subset of ALK-negative inflammatory myofibroblastic tumors. Immunohistochemistry for ROS1 has been shown to correlate with ROS1rearrangement in lung adenocarcinomas. The purpose of this study was to determine whether immunohistochemistry for ROS1 could predict ROS1rearrangement in inflammatory myofibroblastic tumor. In total, 30 inflammatory myofibroblastic tumors were evaluated, including 21 ALK-positive tumors (10 confirmed to harbor ALKrearrangements, with TPM3, CLTC, RANPB2, and FN1fusion partners) and 9 ALK-negative tumors (including 2 known to harbor ROS1rearrangements). Immunohistochemistry was performed on whole tissue sections following pressure cooker antigen retrieval using a rabbit anti-ROS1 monoclonal antibody. The results were scored as ‘positive’ or ‘negative,‘ and the pattern of staining was recorded. Three ALK-negative inflammatory myofibroblastic tumors (including both tumors with known ROS1rearrangements) showed immunoreactivity for ROS1, whereas all ALK-positive inflammatory myofibroblastic tumors were negative for ROS1. One ROS1-positive inflammatory myofibroblastic tumor (with YWHAE-ROS1fusion) showed strong, diffuse cytoplasmic and nuclear staining; one case (with TFG-ROS1fusion) showed weak, diffuse and dot-like cytoplasmic staining; and one case (fusion partner unknown) showed moderate, diffuse and dot-like cytoplasmic staining. Expression of ROS1 correlates with ROS1gene rearrangement in inflammatory myofibroblastic tumor. These findings suggest that immunohistochemistry for ROS1 may be useful to support the diagnosis of a subset of inflammatory myofibroblastic tumors and may select some clinically aggressive cases for targeted therapy directed against ROS1.

Identification of p53-positive cells by immunohistochemistry in bone marrow from primary myelodysplastic syndrome patients correlates with the presence of TP53 mutations and poor prognosis. Mutations in the tumor suppressor gene TP53 are more frequent in therapy-related acute myeloid leukemia and myelodysplastic syndrome than in de novo disease, but the role of p53 immunohistochemistry in the therapy-related setting has not been specifically investigated. We studied p53 protein immunoreactivity in bone marrow biopsies of therapy-related myeloid neoplasms and correlated protein expression with TP53 mutation status, clinicopathologic features and outcome. We first studied 32 patients with therapy-related acute myeloid leukemia and 63 patients with therapy-related myelodysplastic syndrome/chronic myelomonocytic leukemia from one institution and then validated our results in a separate group of 32 patients with therapy-related acute myeloid leukemia and 56 patients with therapy-related myelodysplastic syndrome from a different institution. Strong p53 immunostaining in ≥1% of bone marrow cells was highly predictive of a TP53 gene mutation (P<0.0001) and was strongly associated with a high-risk karyotype (P<0.0001). The presence of ≥1% p53 strongly positive cells was associated with poorer overall and disease-specific survival, particularly in the subset of patients treated with stem-cell transplantation. In a multivariable Cox regression model, the presence of ≥1% p53 strongly expressing cells was an independent prognostic marker for overall survival in both cohorts, with hazard ratios of 3.434 (CI: 1.751–6.735, P<0.0001) and 3.156 (CI: 1.502–6.628, P=0.002). Our data indicate that p53 protein expression, evaluated in bone marrow biopsies by a widely available immunohistochemical method, prognostically stratifies patients with therapy-related myeloid neoplasms independent of other risk factors. p53 immunostaining thus represents an easily applicable method to assess risk in therapy-related acute myeloid leukemia/myelodysplastic syndrome patients.

Inflammatory myofibroblastic tumor is currently regarded as a neoplasm with intermediate biological potential and a wide anatomic distribution. Inflammatory myofibroblastic tumors of the female genital tract are rare, and to date reported cases behaved indolently. We describe, herein, 10 cases of uterine inflammatory myofibroblastic tumor, 3 of which had an aggressive clinical course. Subject age ranged from 29 to 73 years. Tumors were composed of spindle and epithelioid myofibroblastic cells admixed with lymphoplasmacytic infiltrates in a variably myxoid stroma. Two growth patterns, myxoid and fascicular (leiomyoma-like), were noted. All tumors were positive for ALK expression by immunohistochemistry, which was stronger in the myxoid areas. Smooth muscle marker and CD10 expression was variable in extent, but typically positive. Fluorescence in situ hybridization for ALKrearrangements was positive in both fascicular and myxoid areas in all 8 cases tested. Three subjects showed clinical evidence of tumor aggressiveness as defined by extrauterine spread, local recurrence, or distant metastasis. Aggressive tumors were larger, had a higher proportion of myxoid stroma, and higher mitotic activity than indolent tumors. Tumor cell necrosis was seen only in cases with adverse outcome. This is the first report to describe aggressive biological behavior in uterine inflammatory myofibroblastic tumor. This diagnosis is often underappreciated and merits inclusion in the differential diagnosis of myxoid mesenchymal lesions of the uterus, particularly because patients with an aggressive course may benefit from targeted therapy.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare, aggressive malignant neoplasm characterized by small nests and linear arrays of epithelioid cells embedded in a dense collagenous matrix. Very few primary SEFs of bone have been reported. Recognition is critical, as the dense extracellular collagenous matrix can be interpreted as osteoid, leading to misdiagnosis as-osteosarcoma. MUC4 and SATB2 are 2 recently characterized immunohistochemical markers for SEF and osteosarcoma, respectively. In reports to date, osteosarcomas are positive for SATB2 and negative for MUC4, whereas soft tissue SEFs have shown the opposite immunohistochemical profile (SATB2−/MUC4+). The purpose of this study was to characterize the clinicopathologic and immunohistochemical features of 8 primary SEFs of bone. The patients presented at a wide range of ages (25 to 73 y; median 52 y). Tumors mostly involved long bones of the extremities, with 3 cases involving the femur, 2 involving the ulna, and 1 involving the humerus. Other sites of involvement included the second rib (1) and the C6 vertebra (1). Follow-up information was available for 7 patients, 3 of whom developed metastases within 2 years of diagnosis. The other 4 patients were free of local recurrence or metastases at 1, 5, 12, and >84 months of follow-up, respectively. Radiographically, the tumors were predominantly lytic and poorly marginated. Histologically, 6 tumors showed pure SEF morphology, and 2 showed hybrid SEF/low-grade fibromyxoid sarcoma morphology. Focal dystrophic mineralization was seen in 1 case but was limited to areas of necrosis. None of the tumors showed the lace-like pattern of mineralization typical of osteosarcoma. The majority (6/8) of the tumors strongly expressed MUC4. SATB2 was negative in all but 1 case, which showed variable weak to moderate staining in ∼50% of nuclei. In general, the combination of morphology, MUC4 expression, and the absence of SATB2 expression was highly useful in arriving at the correct diagnosis.

The Church of Gesù and the tower of the Cathedral were stricken and damaged by Emilia-Romagna earthquake sequence of May 2012. This paper presents the procedure for the structural identification of the most widespread types of religious monuments. The dynamic behavior was analyzed using the ambient vibrations test to measure the dynamical properties (mode of vibration, frequencies, displacements and damping ratios) of the constructions using a modal identification of output-only systems. The operational modal analysis OMA has been carried out to identify the modal characteristics through poly-reference Least Square Complex Frequency-domain (pLSFC) estimator. The global structural health monitoring was carried out to define the real dynamic behavior of the damaged constructions that are subjected to different mechanism. These researches are useful for the structural rehabilitation and to define the possible changes in the structural behavior.

The paper presents some considerations on the reliability of the available formulas to determine the shear strength of masonry reinforced with FRP (fibre reinforced polymer) material. In detail the outcomes of a model related to the Eurocode 6 is prepared in presence of not usual shear reinforcement as FRP mesh bars jointed to ten surface masonry through steel joints. The model considers the basic contribution due to the masonry material and then add the contribution related to the presence of a material as carbon bars that is characterized by higher behaviour in term of stiffness.

This paper presents a first program of non-destructive tests carried out on two medieval façades and inside the main rooms of Palazzo Ducale in Venice, i.e. the room of Maggior Consiglio and the room of Scrutinio. A probably multiple leaf load-bearing brick masonry and an external cladding of polychrome stones compose these façades under investigation. The aim of the tests concern the improvement of knowledge about the construction technique and the mechanical features of these important historical facades. The program was set up after a preliminary historic investigation. Non-destructive and minor-destructive investigations (i.e. pattern surveys, endoscopic tests and georadar test) on the inner sides of the two walls of the area under examination were carried out for the analytical determination of the construction technique and structural characteristics, not clearly inferable from the literature.Due to the complexity of the structure and the transformations undergone in seven hundred years of life, and to the very limited investigable areas of the internal surface, the results of investigations cannot be extended to the entire structure. Nevertheless, these tests provide valuable clues to give a correct interpretation of the construction technique and to contribute to identify the possible mechanical properties, which provide knowledge about the health state of the building.

The paper presents a critical analysis of the structural response and the level of damage of a historic tower of Santo Stefano of Sessanio that was hit by the main L Aquila earthquake of April 2009. A FE model was constructed to simulate the structural behaviour during the seismic event. The presence of a reinforced concrete slab in the upper part of the tower probably cause a different dynamic behavior compared with the lower masonry circular walls. Have also been investigated boundary conditions at the base, the different mechanical property of masonry and the contribution of the stiffness of the wooden floors.

The City Hall of Mirandola was stricken and damaged by Emilia-Romagna earthquake sequence of May 2012. This paper presents the procedure for the structural monitoring control of a masonry historic building that presents a serious damage pattern. Structural monitoring was carried out with transducers installed to control the serious cracks that regards the main volumes of the building. The global structural health monitoring was useful to define the actual condition of the dynamic behavior of the damaged construction that are subjected to different mechanism. Ground penetrating radar allows to detect the depth of the cracks and the condition of the masonry. These researches are useful also for the structural future rehabilitation and to define the possible changes in the structural behavior.

The research showed focus on the performance comparison between two equivalent frame structure. i.e. the first one made by steel and the second one by all frp (fibre reinforced polymer ) pultruded material. The structure adopted for the analysis is a traditional two floors frame made by connections between columns and beams. The connection has been assumed rigid to simplify the comparison, already very hard and to point out on the overall structural answer of the two different cases. The reason why of the investigation is related to teh need to deep detail the eventually structural benefits in presence of FRP material. However the success is related to a very reduced weight of FRP material (with weight equal to 1600-1800 kg/m3) linked to a not negligible performance in term of strength and durability, even if also the easy employment play a very important rule. The two storeys frame were subjected to static and dynamic actions to analyse also in comparison the response

A CGF Panel (Concrete Glulam Framed Panel) is a concrete panel with a glued laminated timber frame. The experimentation on this new construction system at LabSCo (Laboratory of Strength of Materials) of IUAV University of Venice, inspired a wide research on buildings made of this construction system investigating in different aspect of building behaviour: particularly about mechanical property of the materials, mechanical of the system and building physics. This paper presents the results of quasi-static in-plane tests on single panel and configurations of some different panels. The tests in the laboratory are used for measuring the in-plane strength and stiffness of individual panels and wall sections consist of some panels in order to verify and measure the behavior of the connections between the various parts of the single panel and the connection between the panels. Thanks to the results obtained it was possible carry out the FE model to calibrate the characteristics in relation to experimental data. Finally, in order to compare this constructive system with the well known X-lam systems, on the basis of the calibration of the models we were able to set up a comparable FE model with those of the X-lam wall described in the publication: "Quasi-Static and Pseudo-Dynamic Tests on XLAM Walls and Buildings " inherent in the SOFIE project coordinated by the CNR-IVALSA (Italian National Research Council - Trees and Timber Institute)

The aim of this research regards the evaluation of mechanical performance of a prototype panel made by steel fiber reinforced concrete, SFRC, on the top, and fiber reinforced pultruded sandwich panel, GFRP, on the bottom, subjected to combined moment-shear actions through four-bending test. Two different mechanical solutions were used for the connection of the panels. A first steel connection previously designed and a second one with resin applied uniformly on the surface of GFRP panel. The SFRC-G panel involves the analysis of the weakness of GFRP material due to its very low deformability, the risk of the local instability and the elastic brittle behaviour till the collapse, while steel is obviously characterized by elastic-plastic curve. However in the test proposed the ultimate limit state (SLU) involves first of all the loss of bond strength between materials. The panels length/thickness ratio has been previously designed to give prominence to flexural-shear combined actions and in verifying the connections capacity.

The paper shows the approach toward the construction of a very large Pultruded Fibre Reinforced Polymer (PFRP) temporary structure realized to accommodate future restoration work and to cover a historic church stroked and partially collapsed by 2009 LAquila earthquake. The aim regards the analysis and evaluation of seismic performance of that structure made by very light and elastic-brittle material, as FRP material, in a moment in which there is a loss of technical recommendation for specific calculation in seismic field, indeed actually some deepening already present in literature allows only static field. The covering structure is an all FRP spatial-reticular with elements made by pultrusion process, connection plates by bag molding process and steel bolts. The PFRP structure covers more than 1050 meters squares surface with 32 meters height and only 100 kN weight. Detail performance of first part of PFRP structure through mode vibrations and involved percentage mass deduced by numerical approach with discussion of employments perspectives of PFRP material in seismic zones than traditional material are showed.

Perivascular epithelioid cell tumor (PEComa) belongs to a family of tumors characterized by coexpression of melanocytic and muscle markers. Recent studies have shown that sporadic and tuberous sclerosis complex–associated PEComa may respond to mTOR inhibitors underscoring the importance of recognizing this tumor. However, its occurrence in the gynecologic tract continues to be disputed owing to its common misclassification as other types of uterine sarcoma and its controversial relationship with epithelioid smooth muscle tumors. To more fully characterize PEComa of the female genital tract, 16 cases of gynecologic PEComa were identified (1990 to 2012) and formed the basis of this study. Each case was analyzed for conventional morphologic and immunohistochemical characteristics established for PEComa of extrauterine sites; clinical outcome data were obtained for all cases. The 16 patients were aged 28 to 60 (mean 49; median 50) years, and 1 had a history of tuberous sclerosis complex. Thirteen cases were primary of the uterus, 2 of the adnexa, and 1 of the vagina. Tumor size ranged from 0.3 to 25.0 (mean 8.7) cm. Three patients died of disease, 6 were alive with disease, and 7 were alive without evidence of disease at last follow-up (1 mo to 13 y follow-up; mean 26 mo). All patients with an adverse outcome met established criteria for malignancy as proposed for extrauterine sites (ie, 2 or more features present: size ≥5 cm, high-grade nuclear features, infiltration, necrosis, lymphovascular invasion, or a mitotic rate ≥150 high-power fields). Of the melanocytic markers, HMB45 was most commonly expressed (1616 positive, 100), followed by microphthalmia transcription factor (1112 positive, 92), MelanA (1416 positive, 88), and S100 protein (210 positive, 20). Of the smooth muscle markers, desmin was most commonly expressed (1515 cases, 100), followed by SMA (1415 cases, 93) and h-caldesmon (1112 cases, 92). TFE3 immunopositivity was identified in 5 of 13 cases; however, 3 tested cases were negative for a TFE3 rearrangement by fluorescence in situ hybridization. Current criteria for malignancy appear to be valid in the female genital tract, although modified criteria, as described herein, may be more specific. Awareness of the characteristic features of PEComa is important to help distinguish it from epithelioid smooth muscle tumors and other mimics as PEComa may respond to unique chemotherapeutic regimens.