Health technology assessment through the six sigma approach in abdominoplasty: Scalpel vs electrosurgery.

Abdominoplasty is a surgical procedure conducted to reduce excess abdominal skin and fat and improve body contouring. Despite being commonly performed, it is associated with a risk of complications such as infection, seroma, haematoma and wound dehiscence. To reduce the incidence of complications, different methods are used to create the abdominal flap, i.e., incision with a scalpel or electrosurgery. In this study, health technology assessment (HTA) using the Six Sigma methodology was conducted to compare these incision techniques in patients undergoing abdominoplasty. Two consecutively enroled groups of patients (33 in the scalpel group and 35 in the electrosurgery group) who underwent surgery at a single institution, the University of Campania "Luigi Vanvitelli", were analysed using the drain output as the main outcome for comparison of the incision techniques. While no difference was found regarding haematoma or seroma formation (no cases in either group), the main results also indicate a greater drain output (p-value<0.001) and a greater incidence of dehiscence (p-value=0.056) in patients whose incisions were made through electrosurgery. The combination of HTA and the Six Sigma methodology was useful to prove the possible advantages of creating skin incisions with a scalpel in full abdominoplasty, particularly a significant reduction in the total drain output and a reduction in wound healing problems, namely, wound dehiscence, when compared with electrosurgery, despite considering two limited and heterogeneous groups.

Metal-insulator transition in single crystalline ZnO nanowires.

In this work, we report on the metal-insulator transition and electronic transport properties of single crystalline ZnO nanowires synthetized by means of Chemical Vapor Deposition. After evaluating the effect of adsorbed species on transport properties, the thermally activated conduction mechanism was investigated by temperature-dependent measurements in the range 81.7-250 K revealing that the electronic transport mechanism in these nanostructures is in good agreement with the presence of two thermally activated conduction channels. More importantly, it was observed that the electrical properties of ZnO NWs can be tuned from semiconducting to metallic-like as a function of temperature with a metal-to-insulator transition (MIT) observed at a critical temperature above room temperature (T c âˆ¼ 365 K). Charge density and mobility were investigated by means of field effect measurements in NW field-effect transistor configuration. Results evidenced that the peculiar electronic transport properties of ZnO NWs are related to the high intrinsic n-type doping of these nanostructures that is responsible, at room temperature, of a charge carrier density that lays just below the critical concentration for the MIT. This work shows that native defects, Coulomb interactions and surface states influenced by adsorbed species can significantly influence charge transport in NWs.

Classifying the type of delivery from cardiotocographic signals: A machine learning approach.

BACKGROUND AND OBJECTIVE: Cardiotocography (CTG) is the most employed methodology to monitor the foetus in the prenatal phase. Since the evaluation of CTG is often visual, and hence qualitative and too subjective, some automated methods have been introduced for its assessment. METHODS: In this paper, a custom-made software is exploited to extract 17 features from the available CTG. A preliminary univariate statistical analysis is performed; then, five machine learning algorithms, exploiting ensemble learning, were implemented (J48, Random Forests (RF), Ada-boosting of decision tree (ADA-B), Gradient Boosting and Decorate) through Knime analytics platform to classify patients according to their delivery: vaginal or caesarean section. The dataset is composed by 370 signals collected between 2000 and 2009 in both public and private hospitals. The performance of the algorithms was evaluated using 10 folds cross validation with different evaluation metrics: accuracy, precision, sensitivity, specificity, area under the curve receiver operating characteristic (AUCROC). RESULTS: While only two features were significantly different (gestation week and power expressed by the high frequency band of FHR power spectrum), from the statistical point of view, machine learning results were great. The RF obtained the best results: accuracy (91.1%), sensitivity (90.0%) and AUCROC (96.7%). The ADA-B achieved the highest precision (92.6%) and specificity (93.1%). As expected, the lowest scores were obtained by J48 that was the base classifier employed in all the others empowered implementations. Excluding the J48 results, the AUCROC of all the algorithms was greater than 94.9%. CONCLUSION: In the light of the obtained results, that are greater than those ones found in the literature from comparable researches, it can be stated that the machine learning approach can actually help the physicians in their decision process when evaluating the foetal well-being.

Hydrothermally grown ZnO nanowire array as an oxygen vacancies reservoir for improved resistive switching.

Resistive switching (RS) devices based on self-assembled nanowires (NWs) and nanorods (NRs) represent a fascinating alternative to conventional devices with thin film structure. The high surface-to-volume ratio may indeed provide the possibility of modulating their functionalities through surface effects. However, devices based on NWs usually suffer from low resistive switching performances in terms of operating voltages, endurance and retention capabilities. In this work, we report on the resistive switching behaviour of ZnO NW arrays, grown by hydrothermal synthesis, that exhibit stable, bipolar resistive switching characterized by SET/RESET voltages lower than 3 V, endurance higher than 1100 cycles and resistance state retention of more than 105 s. The physical mechanism underlying these RS performances can be ascribed to nanoionic processes involving the formation/rupture of conductive paths assisted by oxygen-related species in the ZnO active layer. The reported results represent, to the best of our knowledge, the best resistive switching performances observed in ZnO NW arrays in terms of endurance and retention.

Extended memory lifetime in spiking neural networks employing memristive synapses with nonlinear conductance dynamics.

Spiking neural networks (SNNs) employing memristive synapses are capable of life-long online learning. Because of their ability to process and classify large amounts of data in real-time using compact and low-power electronic systems, they promise a substantial technology breakthrough. However, the critical issue that memristor-based SNNs have to face is the fundamental limitation in their memory capacity due to finite resolution of the synaptic elements, which leads to the replacement of old memories with new ones and to a finite memory lifetime. In this study we demonstrate that the nonlinear conductance dynamics of memristive devices can be exploited to improve the memory lifetime of a network. The network is simulated on the basis of a spiking neuron model of mixed-signal digital-analogue sub-threshold neuromorphic CMOS circuits, and on memristive synapse models derived from the experimental nonlinear conductance dynamics of resistive memory devices when stimulated by trains of identical pulses. The network learning circuits implement a spike-based plasticity rule compatible with both spike-timing and rate-based learning rules. In order to get an insight on the memory lifetime of the network, we analyse the learning dynamics in the context of a classical benchmark of neural network learning, that is hand-written digit classification. In the proposed architecture, the memory lifetime and the performance of the network are improved for memristive synapses with nonlinear dynamics with respect to linear synapses with similar resolution. These results demonstrate the importance of following holistic approaches that combine the study of theoretical learning models with the development of neuromorphic CMOS SNNs with memristive devices used to implement life-long on-chip learning.

Resistive switching in sub-micrometric ZnO polycrystalline films.

Resistive switching (RS) devices are considered as the most promising alternative to conventional random access memories. They interestingly offer effective properties in terms of device scalability, low power-consumption, fast read/write operations, high endurance and state retention. Moreover, neuromorphic circuits and synapse-like devices are envisaged with RS modeled as memristors, opening the route toward beyond-Von Neumann computing architectures and intelligent systems. This work investigates how the RS properties of zinc oxide thin films are related to both sputtering deposition process and device configuration, i.e. valence change memory and electrochemical metallization memory (ECM). Different devices, with an oxide thickness ranging from 50-250 nm, are fabricated and deeply characterized. The electrical characterization evidences that, differently from typical nanoscale amorphous oxides employed for resistive RAMs (HfO x , WO x , etc), sub-micrometric thicknesses of polycrystalline ZnO layers with ECM configuration are needed to achieve the most reliable devices. The obtained results are deeply discussed, correlating the RS mechanism to material nanostructure.

Higher serum sclerostin levels and insufficiency of vitamin D are strongly associated with vertebral fractures in hemodialysis patients: a case control study.

In hemodialysis patients, vertebral fractures were associated with elevated sclerostin levels, suggesting that sclerostin could reflect bone fragility in these patients. INTRODUCTION: Fragility fractures are common in hemodialysis patients. The aims of our study were to determine the prevalence of vertebral fracture and analyze associations between sclerostin serum levels and vertebral fractures in hemodialysis patients. METHODS: Ninety-two hemodialysis patients and 100 controls matched for age and sex were studied. Bone mineral density was measured by ultrasonography at non-dominant heel. The markers of bone turnover included serum osteocalcin, C-terminal telopeptide, and sclerostin. All participants underwent radiography of the thoracic and lumbar spine to ascertain the presence of vertebral fractures. RESULTS: Bone ultrasound parameters at calcaneus were significantly lower in hemodialysis patients compared with controls; bone turnover markers and parathyroid hormone level were significantly higher, while serum of 25-OH-D3 was significantly lower in hemodialysis group. One or more moderate or severe vertebral fractures were found in 38 hemodialysis patients, whereas in control group, 10 patients had a vertebral fracture. In hemodialysis group, the comparison between patients with and without vertebral fractures showed that the patients with vertebral fractures had the serum sclerostin levels statistically higher than patients without vertebral, while serum levels of 25-OH-D3 was significantly lower in patients with vertebral fractures compared to the patients without vertebral fractures. Multivariate analysis disclosed that sclerostin levels were associated with an increased risk of vertebral fractures in hemodialysis patients after adjusting for multiple variables. CONCLUSIONS: Our data shows high prevalence of vertebral fractures in hemodialysis patients and that it is associated with elevated sclerostin levels, reflecting bone fragility in these patients.

Biomarker discovery by plasma proteomics in familial Brugada Syndrome.

Brugada Syndrome (BS) is a polygenic inherited cardiac disease characterized by life-threatening arrhythmias and high incidence of sudden death. In this study, two-dimensional gel electrophoresis (2D-PAGE) coupled to mass spectrometry (LC-MS/MS) was used to investigate specific changes in the plasma proteome of BS patients and family members sharing the same gene mutation (SCN5AQ1118X), with the aim to identify novel disease biomarkers. Our data demonstrate that the levels of several proteins were significantly altered in BS patients compared with controls. In particular, apolipoprotein E, prothrombin, vitronectin, complement-factor H, vitamin-D-binding protein, voltage-dependent anion-selective channel protein 3 and clusterin were considerably increased in plasma sample of BS patients, whereas alpha-1-antitrypsin, fibrinogen and angiotensinogen were considerably decreased; moreover, post-translational modifications of antithrombin-III were detected in all affected individuals. On the light of these results, we hypothesize that these proteins might be considered as potential markers for the identification of disease status in BS.

Interplay between steroid receptors and neoplastic progression in sarcoma tumors.

Steroid hormones are expressed at low levels in mesenchymal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT-1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src-dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF-7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFR), androgen receptor (AR), ER, and Src that activates EGF-dependent signaling pathway. In the present study, we demonstrate that, in HT-1080 cells, the Src kinase activity is involved in EGFR phosphorylation and this activity is regulated by an interplay between Src, steroid receptors, and EGFR. In these cells, estradiol (E(2) )/ER and synthetic androgen (R1881)/AR trans-activate EGFR leading to the downstream signaling and to ERK activation. Indeed, the association between ER/AR and EGFR enhances metastatic progression of fibrosarcoma tumors. A population pilot study performed on 16 patients with soft tissue neoplasias highlights that MMPs expression correlates with progression of anaplastic sarcoma as well as overexpression of EGFR. These findings suggest that there is a crosstalk among AR, ER, and EGFR that lead to src activation also in fibrosarcoma cells.

Vapor-phase self-assembled monolayers of aminosilane on plasma-activated silicon substrates.

Aminosilane self-assembled monolayers on silicon substrates have been prepared via a gas-phase procedure based on the consecutive reactions of the aminosilane precursor and water vapor. X-ray photoelectron spectroscopy, atomic force microscopy, and contact angle measurements have been used to characterize the aminosilane layers. For comparison, substrates modified with aminosilane through a liquid-phase procedure have been prepared and characterized by means of the same techniques. The vapor-based procedure was found to yield more uniform layers characterized by fewer and smaller aggregates as compared with liquid-treated substrates. Grazing angles reflection Fourier transform infrared measurements were carried out on the vapor-treated substrates before and after water exposure to investigate the hydrolysis of the alkoxy groups and further reaction to form siloxane bonds. The surface density of amino groups, as estimated through a colorimetric method, is very similar for vapor- and liquid-treated substrates, suggesting a similar reactivity and accessibility of the functional groups on the surface.

Field localization and enhanced Second-Harmonic Generation in silicon-based microcavities.

High-quality amorphous Silicon Nitride (a-Si(1-x)N(x):H) Fabry-Pérot microcavities can show resonant surface Second Harmonic Generation (SHG) effect. We consider two different layouts of planar microcavities with almost identical linear reflectance and show how the structure geometry can strongly affect SHG yield. In particular, a difference of more than one order of magnitude in the SHG intensity is observed when the fundamental beam is tuned at the cavity resonance frequency. We explain this finding on the basis of a theoretical model taking into account the spatial distribution of the electric fields of the pump and harmonic frequencies inside the structure. A satisfactory matching of experimental data with the theoretical model is obtained by considering the source of second-order nonlinearity as limited to surface contributions.

[Bioethics and toxicology]. / Bioetica e tossicologia.

Human activity, involving nature and environment, alters the ecosystems in which we live; the question is whether this activity can be the source of risk and/or the origin of damages to human health. Risk assessment and risk management, connected with its protection, are not only a scientific and technical problem: hazards are real, but risks are social constructions. The role of toxicologists shows subjective features connected with different affiliations (industry, research, government); thus the assumptions and interpretations of risk assessment need to be integrated with wider psychological, social and political perspectives, in particular with ethical choices and values. Within public health personal subjectivities (genetic, biological and social) an adequate value should be given contrary to an abstract and collective entity which may erase and sacrifice subjectivities in favour of a statistical point of view. Public health should be considered as a whole of individual health conditions with regard to prevention, treatment and care.

Problems in testing and risk assessment of endocrine disrupting chemicals with regard to developmental toxicology.

Endocrine disrupting chemicals (EDCs) may affect mammalian development either indirectly (by impairing implantation, placental development, lactation, etc.) or directly, altering the maturation of target tissues. Current regulatory tests for reproductive/developmental toxicity should be carefully evaluated with regard to risk assessment of EDCs, considering hazard identification (are relevant endpoints being assessed?) and dose-response assessment (are sensitive NOEL/dose-response curves being provided?). Many in vitro and in vivo assays for sex steroid disruption are available; provided that the metabolic capacities of the assays are defined, they could be integrated in a sensitive battery for early detection of steroid-disrupting potentials. The screening battery should address further regulatory in vivo tests (e.g. what specific parameters have to be investigated). As regards dose-response, qualitative differences may be observed between lower and higher exposures, showing primary hormone-related effects and frank embryotoxicity, respectively. Other problems concern (a) the identification of critical developmental windows, according to hormone concentrations and/or receptor levels in the developing target tissues; (b) the potential for interactions between chemicals with common mechanism/target (e.g. xenoestrogens); (c) most important, besides sex steroids more attention should be given to other mechanisms of endocrine disruption, e.g., thyroid effects, which can be highly relevant to prenatal and postnatal development.

In vivo studies on possible adverse effects on reproduction of the fungicide methyl thiophanate.

The fungicide methyl thiophanate (MT), widely used to control some of the most common fungal diseases in crops, is metabolized in animals into benzimidazole compounds, including the well-known reproductive toxicant carbendazim. However, standard toxicological tests did not indicate that MT may cause testicular toxicity and/or embryotoxicity, which are typical effects of many benzimidazoles. In the present study some aspects of the MT potential for reproductive toxicity have been assayed by means of two non-conventional models. Following the oral administration of 700 and 1000 mg kg(-1) body wt. for five consecutive days, short-term testicular toxicity was examined in the B6C3F1 mouse through specific parameters (sperm head count, specific enzyme activities, histopathology on days 3-35 post-dosing). In spite of the high doses administered, none of the testicular parameters examined, including histopathology, showed significant alterations as compared to controls at any time post-dosing. Pregnant CD rat dams were administered orally the limit dose of 650 mg kg(-1) body wt. day(-1) during preimplantation (gestational day or GD 2-5) or peri-implantation (GD 6-9) phases; embryos and adnexa were evaluated morphologically on GD 12 as a window for the early observation of embryotoxicity. Evident maternal toxicity was present in both treated groups, whereas only marginal reductions of the growth of embryos and adnexa were observed. A full understanding of MT toxicology will need more quantitative data on metabolism, including plasma kinetics and dosimetry of carbendazim at the relevant targets. Nevertheless, the absence of any clear-cut effect on a number of specific endpoints may provide reassurance that no further testing of MT is needed with regard to testicular toxicity or embryotoxicity.

Developmental toxicity of carbendazim: comparison of no-observed-adverse-effect level and benchmark dose approach.

The benchmark dose (BD) approach has been applied to foetal data from four gavage segment II studies (rat studies 1 and 2, rabbit study, hamster study) on the teratogenic benzimidazole carbendazim. Nineteen parameters were assessed using the log-normal model as a practical tool to derive BDs; good model fitting was observed for all except two parameters. Data were evaluated on a 'per-implant/foetus' basis; BDs were derived from response rate increases of 1, 5, and 10%. The values were compared to the lowest-observed-adverse-effect levels (LOAELs) and no-observed-adverse effect levels (NOAELs) obtained by Fisher's exact test on a 'per-implant/foetus' basis. Frank effects observed only at the top dose and/or small sample size tended to increase the 95% confidence limits and this influenced the determination of BD. Generally, the BD approach provided slightly more conservative estimates than NOAEL; overall, BD01 and BD05 were similar to NOAEL, or even lower for several parameters. The LOAEL in most cases was similar to BD10. Reference doses obtained by dividing BD01 by a 10 or 100 uncertainty factor, corresponded to residual risks of 10(-5) or below. For two critical parameters (hydrocephalus in rat study 1 and resorption rate in the rabbit study) a NOAEL could not be found, whereas a BD was always determined.

Evaluation of the placenta: suggestions for a greater role in developmental toxicology.

Both in human and in rat, two types of placenta are present: the yolk sac (YS) and the chorioallantoic placenta. Histiotrophy, alpha-fetoprotein synthesis and blood cell formation occur in YS of both species. Besides, the midgut, primordial germ cells and possibly immunological structures originate from the YS tissue. The specialised cells of the chorioallantoic placenta attach the embryo to the uterus and form the vascular connections necessary for the nutrient transport. The placenta redirects maternal endocrine, immune and metabolic functions to conceptus advantage. These complex activities are sensitive to direct toxicity. Indirect effects on the placental functions might be elicited by immunomodulators and endocrine disrupters. Some experimental models could be utilised to identify possible toxic effects on placenta. Among the in vitro models the rodent giant yolk sac culture may be used to study the transport of materials, morphological and/or biochemical alterations and biotransformation activity of the visceral YS epithelium. Other in vitro approaches utilise human derived trophoblastic cells and tissues to investigate implantation and perimplantation toxicology. Besides specific studies, in vivo reproductive toxicity tests could pay more attention to the evaluation of placental tissues. Nowadays, some physiologically based pharmacokinetic models for developmental toxicity are also available to describe the disposition of toxic substances and their metabolites during pregnancy in rodents. Thus, more detailed studies on the embryo-foetal placenta may provide an important tool to understand developmental toxicity mechanisms, with particular regard to embryolethality and delayed development.

[Effects of chemical mixtures on embryonic development: examples of experimental models and problems in risk assessment]. / Effetti tossici di miscele chimiche sullo sviluppo prenatale: esempi di modelli sperimentali e problemi relativi alla valutazione del rischio.

Toxicological risk deriving from the exposure to mixtures of toxic substances, the study of possible interactions among them and their mechanisms of action are of special interest in prenatal toxicology. In fact, embryo is a dynamic complex system whose gradual development substantially modulates the extent and type of damages to which it may be sensitive, through specific, critical periods of sensitivity. In this paper, a number of types of interactions among toxic substances which show the same mechanisms of action and/or the same target site, are analysed. Besides, pharmacokinetic interactions among teratogenic agents and substances modulating their metabolism, need specific evaluations because of the wide variability of possible events. In conclusion, risk assessment in prenatal toxicology has to put greater attention to the various types of effect and pharmacokinetic interaction since they might result in an increasing risk at low doses.

[Complex biological systems as experimental and prenatal toxicology models]. / Sistemi biologici complessi come modelli sperimentali e di tossicologia prenatale.

Experimental biomedical sciences have emphasised the use of model systems in the study and understanding of physiological and pathological processes. Developmental biology, genetics and prenatal toxicology, dealing with cellular differentiation, organogenesis and dismorphogenic alterations, have shown that system models, even those far removed from mammals and humans in the zoological scale (e.g. C. elegans, Hydra, Drosophila), can be useful tools for understanding pathogen mechanisms in developmental toxicology. In particular the study of neural tube and its alterations shows how a biologically complex model (such as the laboratory rodent) necessitates, in turn, a series of models to thoroughly analyse and clarify the limits and levels of research.

Effects observed on gestational day 13 in rat embryos exposed to albendazole.

Albendazole (ABZ) was utilized as a model to investigate the pathogenesis of benzimidazole-induced abnormalities. Pregnant Sprague-Dawley rats were treated po with 0, 10, 20, and 30 mg/kg on gestational days (GD) 10 to 12. The embryos were examined on GD 13, as a window for observing the origin of alterations detected at term. Embryolethality and growth reduction showed dose-related increases at the three dose levels. At 10 mg/kg, an increased developmental delay of limb buds and a less than 5% incidence of embryos with abnormal head or shape were detected. At 20 and 30 mg/kg, > 20% of embryos showed morphologic alterations involving mainly shape abnormalities and the development of forelimb buds, branchial bars, eye, and telencephalon; closure of neuropores was unaffected. Dose-response relationships for morphologic alterations showed steeper slopes than for growth reduction and embryolethality.

Prenatal risks deriving from environmental chemicals.

Hundreds of environmental chemicals affect prenatal development in experimental animals. However, only methylmercury and PCBs have been connected with such effects in humans during localized outbreaks of high exposure. In addition growth and development might also be affected by long-term intake of lead, fluorides or PCBs. Several factors may explain the discrepancy between human and animal data: the actual exposure of the population is below threshold levels, unspecific or delayed effects can be difficult to identify, etc. When experimental data are used to assess the hazards for the conceptus, due consideration should be given to actual ability of the study to detect effects. Thus, the limitations in statistical power, the relevance of the parameters considered and low-dose extrapolation should be taken into account. Finally, understanding toxicokinetics and biological mechanisms is needed to perform interspecies comparisons. Three examples of environmental chemicals showing different prenatal hazards are presented: thiabendazole, a benzimidazole compound with a moderate teratogenic potential, but which could represent a good model for biological extrapolation; nitrofen, a diphenyl ether herbicide which may pose a significant hazard, because of its high potential, toxicokinetics, and specific, hormone-like, teratogenic mechanisms; PCBs, well-known, global, cumulative pollutants which are not teratogenic in the laboratory animals, but may affect the human conceptus at high intake levels.