Design Guidelines for Connections of Precast Structures under Seismic Actions

This document has been drafted within Work-Package WP6, “Derivation of design rules” of the project SAFECAST (Performance of Innovative Mechanical Connections in Precast Building Structures under Seismic Conditions), Project FP7-SME-2007-2 Programme – Grant Agreement n. 218417, 2009). The provided guidelines have a theoretical derivation supported by the experimental results of the testing activities and the numerical simulations performed as a part of the project as well as by the general know-how on production practice and international literature on the subject.JRC.G.5-European laboratory for structural assessmen

Treatment of Severe Post-traumatic Bone Defects With Autologous Stem Cells Loaded on Allogeneic Scaffolds.

Mesenchymal stem cells may differentiate into angiogenic and osteoprogenitor cells. The effectiveness of autologous pluripotent mesenchymal cells for treating bone defects has not been investigated in humans. We present a case series to evaluate the rationale of using nucleated cells from autologous bone marrow aspirates in the treatment of severe bone defects that failed to respond to traditional treatments. Ten adult patients (mean age, 49.6-years-old) with severe bone defects were included in this study. Lower limb bone defects were >or=5 cm3 in size, and upper limb defects .or=2 cm3. Before surgery, patients were tested for antibodies to common pathogens. Treatment consisted of bone allogeneic scaffold enriched with bone marrow nucleated cells harvested from the iliac crest and concentrated using an FDA-approved device. Postsurgery clinical and radiographic follow-up was performed at 1, 3, 6, and 12 months. To assess viability, morphology, and immunophenotype, bone marrow nucleated cells were cultured in vitro, tested for sterility, and assayed for the possible replication of adventitious (contaminating) viruses. In 9 of 10 patients, both clinical and radiographic healing of the bone defect along with bone graft integration were observed (mean time, 5.6 months); one patient failed to respond. No post-operative complications were observed. Bone marrow nucleated cells were enriched 4.49-fold by a single concentration step, and these enriched cells were free of microbial contamination. The immunophenotype of adherent cells was compatible with that of mesenchymal stem cells. We detected the replication of Epstein-Barr virus in 2/10 bone marrow cell cultures tested. Hepatitis B virus, cytomegalovirus, parvovirus B19, and endogenous retrovirus HERV-K replication were not detected. Overall, 470 to 1,150 million nucleated cells were grafted into each patient. This case series, with a mean follow-up of almost 2 years, demonstrates that an allogeneic bone scaffold enriched with concentrated autologous bone marrow cells obtained from the iliac crest provides orthopedic surgeons a novel option for treating important bone defects that are unresponsive to traditional therapies

Culture of skeletal myoblasts from human donors aged over 40 years: dynamics of cell growth and expression of differentiation markers

BACKGROUND: Local myogenesis, neoangiogenesis and homing of progenitor cells from the bone marrow appear to contribute to repair of the infarcted myocardium. Implantation into heart tissues of autologous skeletal myoblasts has been associated with improved contractile function in animal models and in humans with acute myocardial ischemia. Since heart infarction is most prevalent in individuals of over 40 years of age, we tested whether culture methods available in our laboratory were adequate to obtain sufficient numbers of differentiated skeletal myoblasts from muscle biopsy specimens obtained from patients aged 41 to 91. METHODS AND RESULTS: No matter of donor age, differentiated skeletal muscle cells could be produced in vitro in amounts adequate for cellular therapy (≥300 millions). Using desmin as a cytoplasmic marker, about 50% cultured cells were differentiated along myogenic lineages and expressed proteins proper of skeletal muscle (myosin type I and II, actin, actinin, spectrin and dystrophin). Cytogenetic alterations were not detected in cultured muscle cells that had undergone at least 10 population doublings. Molecular methods employed for the screening of persistent viral infections evidenced that HCV failed to replicate in muscle cells cultured from one patient with chronic HCV infection. CONCLUSION: The proposed culture methods appear to hold promise for aged patients not only in the field of cardiovascular medicine, but also in the urologic and orthopedic fields

Reliability of follicle-stimulating hormone measurements in serum

BACKGROUND: Follicle-stimulating hormone (FSH), a member of gonadotropin family, is critical for follicular maturation and ovarian steroidogenesis. Serum FSH levels are known to fluctuate during different phases of menstrual cycle in premenopausal women, and increase considerably after the menopause as a result of ovarian function cessation. There is little existing evidence to guide researchers in estimating the reliability of serum FSH measurements. The objective of this study was to assess the reliability of FSH measurement using stored sera from an ongoing prospective cohort – the NYU Women's Health Study. METHODS: Sixty healthy women (16 premenopausal, 44 postmenopausal), who donated at least two blood samples at approximately 1-year intervals were studied. An immunoradiometric assay using a sandwich monoclonal antibodies technique was used to measure FSH levels in serum. RESULTS: The reliability of a single log-transformed FSH measurement, as determined by the intraclass correlation coefficient, was 0.70 for postmenopausal women (95% confidence interval (CI), 0.55–0.82) and 0.09 for premenopausal women (95% CI, 0–0.54). CONCLUSIONS: These results suggest that a single measurement is sufficient to characterize the serum FSH level in postmenopausal women and could be a useful tool in epidemiological research. For premenopausal women, however, the reliability coefficient was low, suggesting that a single determination is insufficient to reliably estimate a woman's true average serum FSH level and repeated measurements are desirable

Assessing the value of CAN-gene mutations using MALDI-TOF MS

Purpose: To identify cancer-linked genes, Sjöblom et al. and Wood et al. performed a genome-wide mutation screening in human breast and colorectal cancers. 140 CAN-genes were found in breast cancer, which in turn contained overall 334 mutations. These mutations could prove useful for diagnostic and therapeutic purposes. Methods: We used a MALDI-TOF MS 40-plex assay for testing 40 loci within 21 high-ranking breast cancer CAN-genes. To confirm mutations, we performed single-plex assays and sequencing. Results: In general, the mutation rate of the analyzed loci in our sample cohort was very low. No mutation from the 40 loci analyzed could be found in the 6 cell lines. In tissue samples, a single breast cancer tissue sample showed heterozygosity at locus c.5834G>A within the ZFYVE26 gene (Zinc finger FYVE domain-containing gene 26). Conclusions: Sjöblom et al./Wood et al. already showed that the vast majority of CAN-genes are mutated at very low frequency. Due to the fact that we only found one mutation in our cohort, we therefore assume that at the selected loci, mutations might be low-frequency events and therefore, more rarely detectable. However, further evaluation of the CAN-gene mutations in larger cohorts should be the aim of further studie

Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations

The present study investigated promoter hypermethylation of TP53 regulatory pathways providing a potential link between epigenetic changes and mitochondrial DNA (mtDNA) alterations in breast cancer patients lacking a TP53 mutation. The possibility of using the cancer-specific alterations in serum samples as a blood-based test was also explored. Triple-matched samples (cancerous tissues, matched adjacent normal tissues and serum samples) from breast cancer patients were screened for TP53 mutations, and the promoter methylation profile of P14ARF, MDM2, TP53 and PTEN genes was analyzed as well as mtDNA alterations, including D-loop mutations and mtDNA content. In the studied cohort, no mutation was found in TP53 (DNA-binding domain). Comparison of P14ARF and PTEN methylation patterns showed significant hypermethylation levels in tumor tissues (P < 0.05 and <0.01, respectively) whereas the TP53 tumor suppressor gene was not hypermethylated (P < 0.511). The proportion of PTEN methylation was significantly higher in serum than in the normal tissues and it has a significant correlation to tumor tissues (P < 0.05). mtDNA analysis revealed 36.36% somatic and 90.91% germline mutations in the D-loop region and also significant mtDNA depletion in tumor tissues (P < 0.01). In addition, the mtDNA content in matched serum was significantly lower than in the normal tissues (P < 0.05). These data can provide an insight into the management of a therapeutic approach based on the reversal of epigenetic silencing of the crucial genes involved in regulatory pathways of the tumor suppressor TP53. Additionally, release of significant aberrant methylated PTEN in matched serum samples might represent a promising biomarker for breast cance

Variation of hemoglobin levels in normal Italian populations from genetic isolates.

Normal hemoglobin levels vary greatly according to genetic and acquired factors. As a consequence there is no general agreement on the definition of anemia in terms of hemoglobin levels. Here we compare the hemoglobin levels of subjects recruited from normal genetically isolated Italian populations whose medical history, life style habits and results of laboratory tests are available. After the exclusion of pathological samples we analyzed the hemoglobin levels of 3,849 subjects (1,661 males and 2,188 females) and evaluated the hemoglobin heritability. Normal subjects of different age groups from a northern Italian isolate have significantly higher hemoglobin levels when compared to matched subjects of southern Italian isolates. The estimated heritability of hemoglobin levels ranges from 0.34 to 0.42 in the different isolates. Our study provides a dataset of hemoglobin levels for normal subjects of different geographical origin and indicate that hemoglobin levels are substantially influenced by heritable components

Assicurazioni e sviluppo: lezioni dalla storia

Il volume raccoglie contributi e testimonianze di studiosi sul tema del rapporto tra le vicende del settore assicurativo e lo sviluppo economico e sociale del Paese. Pubblicato in occasione della ricorrenza dei 150 anni dell’Unità d’Italia, documenta non solo il rilevante ruolo sociale svolto da questa importante componente dell’industria finanziaria nel sostenere in vario modo lo sviluppo, e il modello di sviluppo nelle diverse fasi storiche della storia post-unitaria. Testimonia anche come l’andamento del settore si sia adattato e abbia concorso a caratterizzare i rapporti tra pubblico e privato nella struttura economico-industriale, la domanda di protezione e di copertura dei rischi proveniente dalle imprese e dalle famiglie, l’articolazione e il funzionamento dei servizi, delle garanzie pubbliche e delle forme di protezione offerte dallo Stato sociale, lo stato delle tecnologie, della ricerca economica e statistica e dell’efficienza della pubblica amministrazione. L’obiettivo è quello di capire e proiettare sul futuro il ruolo del settore assicurativo di fronte ai grandi cambiamenti in corso e agli scenari di rischio in evoluzione. Tra gli interventi inclusi nel volume quelli di Giuliano Amato, Pierluigi Ciocca, Elsa Fornero, Robin Pearson e Gianni Toniolo)

A View on the Implementation of the European Open Science Cloud

This paper outlines the discussion and presents the main outcomes of two workshops held in Padova and Venice in August–September 2017 on Open Science and the European Open Science Cloud (EOSC) initiative. The paper describes the three layers on which EOSC is grounded: governance, service and data layer, and discusses the new emerging roles for researchers and research support services. Suggestions about the EOSC implementation at local level are given

The challenge of measuring circulating estradiol at low concentrations

Demand for measuring estradiol at low concentrations is increasing, and the widely used 'direct' radioimmunoassays that do not require a preliminary organic purification step may be inadequate in patient care because of their limited accuracy. In observational epidemiology, however, the main concern is to obtain a correct ranking of individuals' hormone concentration relative to the true level (as determined through a 'gold standard'). Despite differences in the absolute scale of measured and true concentrations, correct ranking will permit calculation of unbiased estimates of hormone–disease associations. In prospective studies, the major concerns are the limited volume of often irreplaceable specimens and the need to perform a large number of assays within a reasonable period of time. Organic purification is often not feasible because of sample volume requirements and logistic difficulties, and so the development of accurate, rapid and inexpensive methods to measure sex steroids at low concentrations would represent a valuable new research tool for both clinicians and epidemiologists