Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center

Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.

Bioremediation of PAHs - Limitations and soultions

Introduction 1.1 Occurrence of polycyclic aromatic hydrocarbons (PAH) in the environment Worldwide industrial and agricultural developments have released a large number of natural and synthetic hazardous compounds into the environment due to careless waste disposal, illegal waste dumping and accidental spills. As a result, there are numerous sites in the world that require cleanup of soils and groundwater. Polycyclic aromatic hydrocarbons (PAHs) are one of the major groups of these contaminants (Da Silva et al., 2003). PAHs constitute a diverse class of organic compounds consisting of two or more aromatic rings with various structural configurations (Prabhu and Phale, 2003). Being a derivative of benzene, PAHs are thermodynamically stable. In addition, these chemicals tend to adhere to particle surfaces, such as soils, because of their low water solubility and strong hydrophobicity, and this results in greater persistence under natural conditions. This persistence coupled with their potential carcinogenicity makes PAHs problematic environmental contaminants (Cerniglia, 1992; Sutherland, 1992). PAHs are widely found in high concentrations at many industrial sites, particularly those associated with petroleum, gas production and wood preserving industries (Wilson and Jones, 1993). 1.2 Remediation technologies Conventional techniques used for the remediation of soil polluted with organic contaminants include excavation of the contaminated soil and disposal to a landfill or capping - containment - of the contaminated areas of a site. These methods have some drawbacks. The first method simply moves the contamination elsewhere and may create significant risks in the excavation, handling and transport of hazardous material. Additionally, it is very difficult and increasingly expensive to find new landfill sites for the final disposal of the material. The cap and containment method is only an interim solution since the contamination remains on site, requiring monitoring and maintenance of the isolation barriers long into the future, with all the associated costs and potential liability. A better approach than these traditional methods is to completely destroy the pollutants, if possible, or transform them into harmless substances. Some technologies that have been used are high-temperature incineration and various types of chemical decomposition (for example, base-catalyzed dechlorination, UV oxidation). However, these methods have significant disadvantages, principally their technological complexity, high cost , and the lack of public acceptance. Bioremediation, on the contrast, is a promising option for the complete removal and destruction of contaminants. 1.3 Bioremediation of PAH contaminated soil & groundwater Bioremediation is the use of living organisms, primarily microorganisms, to degrade or detoxify hazardous wastes into harmless substances such as carbon dioxide, water and cell biomass Most PAHs are biodegradable unter natural conditions (Da Silva et al., 2003; Meysami and Baheri, 2003) and bioremediation for cleanup of PAH wastes has been extensively studied at both laboratory and commercial levels- It has been implemented at a number of contaminated sites, including the cleanup of the Exxon Valdez oil spill in Prince William Sound, Alaska in 1989, the Mega Borg spill off the Texas coast in 1990 and the Burgan Oil Field, Kuwait in 1994 (Purwaningsih, 2002). Different strategies for PAH bioremediation, such as in situ , ex situ or on site bioremediation were developed in recent years. In situ bioremediation is a technique that is applied to soil and groundwater at the site without removing the contaminated soil or groundwater, based on the provision of optimum conditions for microbiological contaminant breakdown.. Ex situ bioremediation of PAHs, on the other hand, is a technique applied to soil and groundwater which has been removed from the site via excavation (soil) or pumping (water). Hazardous contaminants are converted in controlled bioreactors into harmless compounds in an efficient manner. 1.4 Bioavailability of PAH in the subsurface Frequently, PAH contamination in the environment is occurs as contaminants that are sorbed onto soilparticles rather than in phase (NAPL, non aqueous phase liquids). It is known that the biodegradation rate of most PAHs sorbed onto soil is far lower than rates measured in solution cultures of microorganisms with pure solid pollutants (Alexander and Scow, 1989; Hamaker, 1972). It is generally believed that only that fraction of PAHs dissolved in the solution can be metabolized by microorganisms in soil. The amount of contaminant that can be readily taken up and degraded by microorganisms is defined as bioavailability (Bosma et al., 1997; Maier, 2000). Two phenomena have been suggested to cause the low bioavailability of PAHs in soil (Danielsson, 2000). The first one is strong adsorption of the contaminants to the soil constituents which then leads to very slow release rates of contaminants to the aqueous phase. Sorption is often well correlated with soil organic matter content (Means, 1980) and significantly reduces biodegradation (Manilal and Alexander, 1991). The second phenomenon is slow mass transfer of pollutants, such as pore diffusion in the soil aggregates or diffusion in the organic matter in the soil. The complex set of these physical, chemical and biological processes is schematically illustrated in Figure 1. As shown in Figure 1, biodegradation processes are taking place in the soil solution while diffusion processes occur in the narrow pores in and between soil aggregates (Danielsson, 2000). Seemingly contradictory studies can be found in the literature that indicate the rate and final extent of metabolism may be either lower or higher for sorbed PAHs by soil than those for pure PAHs (Van Loosdrecht et al., 1990). These contrasting results demonstrate that the bioavailability of organic contaminants sorbed onto soil is far from being well understood. Besides bioavailability, there are several other factors influencing the rate and extent of biodegradation of PAHs in soil including microbial population characteristics, physical and chemical properties of PAHs and environmental factors (temperature, moisture, pH, degree of contamination). Figure 1: Schematic diagram showing possible rate-limiting processes during bioremediation of hydrophobic organic contaminants in a contaminated soil-water system (not to scale) (Danielsson, 2000). 1.5 Increasing the bioavailability of PAH in soil Attempts to improve the biodegradation of PAHs in soil by increasing their bioavailability include the use of surfactants , solvents or solubility enhancers.. However, introduction of synthetic surfactant may result in the addition of one more pollutant. (Wang and Brusseau, 1993).A study conducted by Mulder et al. showed that the introduction of hydropropyl-ß-cyclodextrin (HPCD), a well-known PAH solubility enhancer, significantly increased the solubilization of PAHs although it did not improve the biodegradation rate of PAHs (Mulder et al., 1998), indicating that further research is required in order to develop a feasible and efficient remediation method. Enhancing the extent of PAHs mass transfer from the soil phase to the liquid might prove an efficient and environmentally low-risk alternative way of addressing the problem of slow PAH biodegradation in soil.

Previsione del comportamento dinamico e sismico di un edificio a tre piani in scala reale costituito da pareti sandwich in C.A. gettato in opera da provare su tavola vibrante

INDICE INTRODUZIONE 1 1. DESCRIZIONE DEL SISTEMA COSTRUTTIVO 5 1.1 I pannelli modulari 5 1.2 Le pareti tozze in cemento armato gettate in opera realizzate con la tecnologia del pannello di supporto in polistirene 5 1.3 La connessione tra le pareti e la fondazione 6 1.4 Le connessioni tra pareti ortogonali 7 1.5 Le connessioni tra pareti e solai 7 1.6 Il sistema strutturale così ottenuto e le sue caratteristiche salienti 8 2. RICERCA BIBLIOGRAFICA 11 2.1 Pareti tozze e pareti snelle 11 2.2 Il comportamento scatolare 13 2.3 I muri sandwich 14 2.4 Il “ferro-cemento” 15 3. DATI DI PARTENZA 19 3.1 Schema geometrico - architettonico definitivo 19 3.2 Abaco delle sezioni e delle armature 21 3.3 Materiali e resistenze 22 3.4 Valutazione del momento di inerzia delle pareti estese debolmente armate 23 3.4.1 Generalità 23 3.4.2 Caratteristiche degli elementi provati 23 3.4.3 Formulazioni analitiche 23 3.4.4 Considerazioni sulla deformabilità dei pannelli debolmente armati 24 3.4.5 Confronto tra rigidezze sperimentali e rigidezze valutate analiticamente 26 3.4.6 Stima di un modulo elastico equivalente 26 4. ANALISI DEI CARICHI 29 4.1 Stima dei carichi di progetto della struttura 29 4.1.1 Stima dei pesi di piano 30 4.1.2 Tabella riassuntiva dei pesi di piano 31 4.2 Analisi dei carichi da applicare in fase di prova 32 4.2.1 Pesi di piano 34 4.2.2 Tabella riassuntiva dei pesi di piano 35 4.3 Pesi della struttura 36 4.3.1 Ripartizione del carico sulle pareti parallele e ortogonali 36 5. DESCRIZIONE DEL MODELLO AGLI ELEMENTI FINITI 37 5.1 Caratteristiche di modellazione 37 5.2 Caratteristiche geometriche del modello 38 5.3 Analisi dei carichi 41 5.4 Modello con shell costituite da un solo layer 43 5.4.1 Modellazione dei solai 43 5.4.2 Modellazione delle pareti 44 5.4.3 Descrizione delle caratteristiche dei materiali 46 5.4.3.1 Comportamento lineare dei materiali 46 6. ANALISI DEL COMPORTAMENTO STATICO DELLA STRUTTURA 49 6.1 Azioni statiche 49 6.2 Analisi statica 49 7. ANALISI DEL COMPORTAMENTO DINAMICO DELLA STRUTTURA 51 7.1 Determinazione del periodo proprio della struttura con il modello FEM 51 7.1.1 Modi di vibrare corrispondenti al modello con solai e pareti costituiti da elementi shell 51 7.1.1.1 Modi di vibrare con modulo pari a E 51 7.1.1.2 Modi di vibrare con modulo pari a 0,5E 51 7.1.1.3 Modi di vibrare con modulo pari a 0,1E 51 7.1.2 Modi di vibrare corrispondenti al modello con solai infinitamente rigidi e pareti costituite da elementi shell 52 7.1.2.1 Modi di vibrare con modulo pari a E 52 7.1.2.2 Modi di vibrare con modulo pari a 0,5E 52 7.1.2.3 Modi di vibrare con modulo pari a 0,1E: 52 7.1.3 Modi di vibrare corrispondenti al modello con solai irrigiditi con bielle e pareti costituite da elementi shell 53 7.1.3.1 Modi di vibrare con modulo pari a E 53 7.1.3.2 Modi di vibrare con modulo pari a 0,5E 53 7.1.3.3 Modi di vibrare con modulo pari a 0,1E 53 7.2 Calcolo del periodo proprio della struttura assimilandola ad un oscillatore semplice 59 7.2.1 Analisi svolta assumendo l’azione del sisma in ingresso in direzione X-X 59 7.2.1.1 Analisi svolta assumendo il modulo elastico E pari a 300000 Kg/cm2 59 7.2.1.1.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari ad E 59 7.2.1.1.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 61 7.2.1.1.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 63 7.2.1.1.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 66 7.2.1.2 Analisi svolta assumendo il modulo elastico E pari a 150000 Kg/cm2 69 7.2.1.2.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,5E 69 7.2.1.2.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,5E 71 7.2.1.2.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 73 7.2.1.2.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 76 7.2.1.3 Analisi svolta assumendo il modulo elastico E pari a 30000 Kg/cm2 79 7.2.1.3.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,1E 79 7.2.1.3.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,1E 81 7.2.1.3.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 83 7.2.1.3.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 86 7.2.2 Analisi svolta assumendo l’azione del sisma in ingresso in direzione Y-Y 89 7.2.2.1 Analisi svolta assumendo il modulo elastico E pari a 300000 Kg/cm2 89 7.2.2.1.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari ad E 89 7.2.2.1.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 91 7.2.2.1.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 93 7.2.2.1.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 98 7.2.2.1.5 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari ad E 103 7.2.2.1.6 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 105 7.2.2.1.7 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 107 7.2.2.1.8 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari ad E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 112 7.2.2.2 Analisi svolta assumendo il modulo elastico E pari a 150000 Kg/cm2 117 7.2.2.2.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,5E 117 7.2.2.2.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,5E 119 7.2.2.2.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 121 7.2.2.2.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,5 E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 126 7.2.2.2.5 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,5 E 131 7.2.2.2.6 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 133 7.2.2.2.7 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,5E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 135 7.2.2.2.8 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,5E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 140 7.2.2.3 Analisi svolta assumendo il modulo elastico E pari a 30000 Kg/cm2 145 7.2.2.3.1 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,1E 145 7.2.2.3.2 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari a 0,1E 147 7.2.2.3.3 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 149 7.2.2.3.4 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 154 7.2.2.3.5 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H e modulo elastico assunto pari a 0,1 E 159 7.2.2.3.6 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H e modulo elastico assunto pari ad E 161 7.2.2.3.7 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 2/3 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 163 7.2.2.3.8 Determinazione del periodo proprio della struttura considerando la massa complessiva concentrata a 1/2 H, modulo elastico assunto pari a 0,1E, e struttura resistente costituita dai soli “maschi murari” delle pareti parallele all’azione del sisma 168 7.3 Calcolo del periodo proprio della struttura approssimato utilizzando espressioni analitiche 174 7.3.1 Approssimazione della struttura ad una mensola incastrata di peso Q=ql avente un peso P gravante all’estremo libero 174 7.3.1.1 Riferimenti teorici: sostituzione di masse distribuite con masse concentrate 174 7.3.1.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 177 7.3.1.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 179 7.3.2 Approssimazione della struttura ad una mensola incastrata alla base, di peso Q=ql, avente un peso P gravante all’estremo libero e struttura resistente costituita dai soli “maschi murari”delle pareti parallele all’azione del sisma 181 7.3.2.1 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 181 7.3.2.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 186 7.3.3 Approssimazione della struttura ad un portale avente peso Qp = peso di un piedritto, Qt=peso del traverso e un peso P gravante sul traverso medesimo 191 7.3.3.1 Riferimenti teorici: sostituzione di masse distribuite con masse concentrate 191 7.3.3.2 Applicazione allo specifico caso di studio in esame con modulo ellastico E=300000 kg/cm2 192 7.3.3.3 Applicazione allo specifico caso di studio in esame con modulo ellastico E=30000 kg/cm2 194 7.3.4 Approssimazione della struttura ad un portale di peso Qp = peso di un piedritto, Qt=peso del traverso e avente un peso P gravante sul traverso medesimo e struttura resistente costituita dai soli “maschi murari”delle pareti parallele all’azione del sisma 196 7.3.4.1 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 196 7.3.4.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 201 7.3.5 Approssimazione della struttura ad una mensola incastrata di peso Q=ql avente le masse m1,m2....mn concentrate nei punti 1,2….n 206 7.3.5.1 Riferimenti teorici: metodo approssimato 206 7.3.5.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 207 7.3.5.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 209 7.3.6 Approssimazione della struttura ad un telaio deformabile con tavi infinitamente rigide 211 7.3.6.1 Riferimenti teorici: vibrazioni dei telai 211 7.3.6.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 212 7.3.6.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 215 7.3.7 Approssimazione della struttura ad una mensola incastrata di peso Q=ql avente masse m1,m2....mn concentrate nei punti 1,2….n e studiata come un sistema continuo 218 7.3.7.1 Riferimenti teorici: metodo energetico; Masse ripartite e concentrate; Formula di Dunkerley 218 7.3.7.1.1 Il metodo energetico 218 7.3.7.1.2 Masse ripartite e concentrate. Formula di Dunkerley 219 7.3.7.2 Applicazione allo specifico caso di studio in esame con modulo elastico E=300000 kg/cm2 221 7.3.7.3 Applicazione allo specifico caso di studio in esame con modulo elastico E=30000 kg/cm2 226 7.4 Calcolo del periodo della struttura approssimato mediante telaio equivalente 232 7.4.1 Dati geometrici relativi al telaio equivalente e determinazione dei carichi agenti su di esso 232 7.4.1.1 Determinazione del periodo proprio della struttura assumendo diversi valori del modulo elastico E 233 7.5 Conclusioni 234 7.5.1 Comparazione dei risultati relativi alla schematizzazione dell’edificio con una struttura ad un grado di libertà 234 7.5.2 Comparazione dei risultati relativi alla schematizzazione dell’edificio con una struttura a più gradi di libertà e a sistema continuo 236 8. ANALISI DEL COMPORTAMENTO SISMICO DELLA STRUTTURA 239 8.1 Modello con shell costituite da un solo layer 239 8.1.1 Analisi dinamica modale con spettro di risposta avente un valore di PGA pari a 0,1g 239 8.1.1.1 Generalità 239 8.1.1.2 Sollecitazioni e tensioni sulla sezione di base 242 8.1.1.2.1 Combinazione di carico ”Carichi verticali più Spettro di Risposta scalato ad un valore di PGA pari a 0,1g” 242 8.1.1.2.2 Combinazione di carico ”Spettro di Risposta scalato ad un valore di 0,1g di PGA” 245 8.1.1.3 Spostamenti di piano 248 8.1.1.4 Accelerazioni di piano 248 8.1.2 Analisi Time-History lineare con accelerogramma caratterizzato da un valore di PGA pari a 0,1g 249 8.1.2.1 Generalità 249 8.1.2.2 Sollecitazioni e tensioni sulla sezione di base 251 8.1.2.2.1 Combinazione di carico ” Carichi verticali più Accelerogramma agente in direzione Ye avente una PGA pari a 0,1g” 251 8.1.2.2.2 Combinazione di carico ” Accelerogramma agente in direzione Y avente un valore di PGA pari a 0,1g ” 254 8.1.2.3 Spostamenti di piano assoluti 257 8.1.2.4 Spostamenti di piano relativi 260 8.1.2.5 Accelerazioni di piano assolute 262 8.1.3 Analisi dinamica modale con spettro di risposta avente un valore di PGA pari a 0,3g 264 8.1.3.1 Generalità 264 8.1.3.2 Sollecitazioni e tensioni sulla sezione di base 265 8.1.

Untersuchungen zur Induktion von Filopodien durch das Amyloid Precursor Like Protein 1 (APLP1), ein Mitglied der APP-Genfamilie

Die Alzheimer Krankheit ist eine fortschreitendende Demenzerkrankung von der in Deutschland ca. 1,6 Millionen Menschen betroffen sind. Im Gehirn der Patienten finden sich sogenannte amyloide Plaques, deren Hauptbestandteil das Aβ-Protein ist. Dieses Peptid ist ein Spaltprodukt des APP-Proteins (engl. amyloid precursor protein). APP ist das namensgebende Mitglied der APP-Proteinfamilie zu der neben APP die beiden APP-Homologen APLP1 und APLP2 (engl. amyloid precursor like protein) gehören. Obwohl inzwischen über die pathologische Rolle dieser Proteinfamilie bei der Alzheimer Krankheit vieles bekannt ist, bleiben die physiologischen Funktionen dieser Proteine bisher größtenteils ungeklärt. Die vorliegende Arbeit beschreibt erstmals einen APLP1-spezifischen Effekt auf die Ausbildung von Filopodien. Sowohl das humane als auch das murine APLP1 induzierten nach transienter Überexpression die Bildung zahlreicher filopodialer Fortsätze auf der Membran von PC12-Zellen. Vergleichbare Resultate konnten mit beiden APLP1-Proteinen auch auf der Membran von embryonalen (E18.5), cortikalen Neuronen der Ratte gezeigt werden. Dass APLP1 einen derartigen Effekt auf Neuronen und PC12-Zellen zeigt, begründet die Annahme, dass APLP1 in vivo eine Funktion bei der Entwicklung und Differenzierung von Neuronen übernimmt. Anhand von Versuchen mit deletierten APLP1-Proteinen und APLP1/APLP2-Chimärproteinen konnte gezeigt werden, dass die von Exon 5 und Exon 6 codierten Bereiche des APLP1 für die Induktion der Filopodien essentiell sind. Unter Einbeziehung von in ihrer räumlichen Struktur bereits bekannten Domänen und aufgrund von Homologievergleichen der primären Aminosäuresequenz dieser Region mit entsprechenden Bereichen der APP- bzw. APLP2-Proteine wurde die wahrscheinliche Lage der Filopodien-induzierenden Domäne innerhalb des von Exon 6 codierten Bereiches diskutiert. Es konnte ferner gezeigt werden, dass die untersuchte Induktion von Filopodien durch die sogenannte α-Sekretierung moduliert werden kann. Unter den gewählten Versuchsbedingungen war nur membranständiges APLP1, nicht aber sekretiertes APLP1 in der Lage, Filopodien zu induzieren. Abschliessend wurden Ergebnisse gezeigt, die erste Einblicke in Signalkaskaden erlauben, die von APLP1 angesteuert werden und so die Enstehung der Filopodien auslösen. Bezüglich des primären Prozesses der Signalkaskade, der Bindung von APLP1 an einen bisher unbekannten Rezeptor, wurde die Möglichkeit diskutiert, ob APP oder APLP2 oder sogar APLP1 selbst als Rezeptor fungieren könnten. Die beobachteten Prozesse nach Überexpression von APLP1 entsprechen vermutlich einer physiologischen Funktion bei der Differenzierung von Neuronen, die mit der Interaktion einer extrazellulär gelegenen Domäne mit einem Rezeptor beginnt, die Aktivierung einer Signalkaskade zur Akrinreorganisation zu Folge hat und die Entstehung filopodialer Strukturen auslöst.

Diagnosi prenatale delle malformazioni fetali: ecografia e risonanza magnetica a confronto in 11 anni di esperienza

Obiettivo: Valutare l’accuratezza reciproca dell’ecografia “esperta” e della risonanza magnetica nelle diagnosi prenatale delle anomalie congenite. Materiali e metodi: Sono stati retrospettivamente valutati tutti i casi di malformazioni fetali sottoposte a ecografia “esperta” e risonanza magnetica nel nostro Policlinico da Ottobre 2001 a Ottobre 2012. L’età gestazionale media all’ecografia e alla risonanza magnetica sono state rispettivamente di 28 e 30 settimane. La diagnosi ecografica è stata confrontata con la risonanza e quindi con la diagnosi postnatale. Risultati: sono stati selezionati 383 casi, con diagnosi ecografica o sospetta malformazione fetale “complessa” o anamnesi ostetrica positiva infezioni prenatali, valutati con ecografia “esperta”, risonanza magnetica e completi di follow up. La popolazione di studio include: 196 anomalie del sistema nervoso centrale (51,2%), 73 difetti toracici (19,1%), 20 anomalie dell’area viso-collo (5,2%), 29 malformazioni del tratto gastrointestinale (7,6%), 37 difetti genito-urinari (9,7%) e 28 casi con altra indicazione (7,3%). Una concordanza tra ecografia, risonanza e diagnosi postnatale è stata osservata in 289 casi (75,5%) ed è stata maggiore per le anomalie del sistema nervoso centrale 156/196 casi (79,6%) rispetto ai difetti congeniti degli altri distretti anatomici 133/187 (71,1%). La risonanza ha aggiunto importanti informazioni diagnostiche in 42 casi (11%): 21 anomalie del sistema nervoso centrale, 2 difetti dell’area viso collo, 7 malformazioni toraciche, 6 anomalie del tratto gastrointestinale, 5 dell’apparato genitourinario e 1 caso di sospetta emivertebra lombare. L’ecografia è stata più accurata della risonanza in 15 casi (3,9%). In 37 casi (9,7%) entrambe le tecniche hanno dato esito diverso rispetto agli accertamenti postnatali. Conclusioni: l’ecografia prenatale rimane a tutt’oggi la principale metodica di imaging fetale. In alcuni casi complessi e/o dubbi sia del sistema nervoso centrale sia degli altri distretti anatomici la risonanza può aggiungere informazioni rilevanti.

Sozialmedizinische Aspekte der medizinischen Versorgung gehörloser Menschen in Deutschland

Einleitung: Die Besonderheiten in der Gesundheitsversorgung von gehörlosen Bürgerinnen und Bürgern in Deutschland sind weitgehend unbekannt. Schätzungsweise 41.500 bis zu 80.000 Menschen sind in Deutschland von Geburt an gehörlos oder früh ertaubt. Diese Gehörlosengemeinschaft verwendet vorrangig die Deutsche Gebärdensprache, die seit 2002 per Gesetzgebung als selbstständige Sprache in Deutschland amtlich anerkannt ist. Der Gesetzgeber hat vorgesehen, dass ein von der Krankenversicherung bezahlter Dolmetscher bei einem Arztbesuch bestellt werden kann. Erkenntnisse, inwieweit dies unter den Betroffenen bekannt ist und genutzt wird, liegen nicht vor. Ebenso sind Annahmen, dass gehörlose Patienten in einer vorrangig von Hörenden gestalteten Gesundheitsversorgung mutmaßlich auf Probleme, Barrieren und Vorurteile stoßen, in Deutschland nicht systematisch untersucht. Die vorliegende Arbeit gibt erstmalig anhand eines größeren Studienkollektivs einen sozialmedizinischen Einblick in den Gesundheitsversorgungszustand von Gehörlosen in Deutschland. Methodik: Im Rahmen einer Vorstudie wurden 2009 zunächst qualitative Experteninterviews geführt, um den Zustand der medizinischen Versorgung von Gehörlosen zu explorieren und Problemfelder zu identifizieren. Anschließend wurde für die Hauptstudie auf der Grundlage der Experteninterviews ein quantitativer Online-Fragebogen mit Gebärdensprachvideos entwickelt und erstmalig in der sozialmedizinischen Gehörlosenforschung eingesetzt. Die gehörlosen Teilnehmer wurden über etablierte Internetportale für Gehörlose und mit Hilfe von Gehörlosenverbänden und Selbsthilfegruppen sowie einer Pressemitteilung rekrutiert. Insgesamt wurden den Teilnehmern bis zu 85 Fragen zu sozioökonomischen Daten, Dolmetschernutzung, Arzt-Patienten-Beziehung und häufig auftretenden Problemen gestellt. Es wurden absolute und relative Häufigkeiten bestimmt und mittels Chi2-Test bzw. exaktem Fisher-Test auf geschlechtsspezifische Unterschiede geprüft. Alle Tests wurden zweiseitig mit der lokalen Irrtumswahrscheinlichkeit α = 0,05 durchgeführt. Ergebnisse: Am Ende der Feldphase verzeichnete die automatische Datenbank 1369 vollständig bearbeitete Fragebögen. 843 entsprachen den a-priori definierten Auswertungskriterien (volljährige Personen, gehörlos, keine fehlenden Angaben in wesentlichen Zielfragen). Häufigstes Ausschlusskriterium war ein anderer Hörstatus als Gehörlosigkeit. Etwa die Hälfte der 831 Teilnehmer (45,1% bzw. 52,8%) schätzte trotz ausreichender Schulbildung ihre Lese- bzw. Schreibkompetenz als mäßig bis schlecht ein. Zeitdruck und Kommunikationsprobleme belasteten bei 66,7% und 71,1% der Teilnehmer bereits einmal einen Arztbesuch. Von 56,6% der Teilnehmer wurde angegeben, dass Hilflosigkeits- und Abhängigkeitsgefühle beim Arztbesuch auftraten. Falsche Diagnosen auf Grund von Kommunikationsproblemen wurden von 43,3% der Teilnehmer vermutet. 17,7% der Teilnehmer gaben an, sich bereits einmal aktiv um psychotherapeutische Unterstützung bemüht zu haben. Gebärdensprachkompetente Ärzte wären optimal um die Kommunikation zu verbessern, aber auch Dolmetscher spielen eine große Rolle in der Kommunikation. 31,4% der gehörlosen Teilnehmer gaben jedoch an, nicht über die aktuellen Regelungen zur Kostenübernahme bei Dolmetschereinsätzen informiert zu sein. Dies betraf besonders jüngere, wenig gebildete und stark auf die eigene Familie hin orientierte Gehörlose. Wesentliche geschlechtsspezifische Unterschiede konnten nicht festgestellt werden. Diskussion: Geht man von etwa 80.000 Gehörlosen in Deutschland aus, konnten mit der Mainzer Gehörlosen-Studie etwa 1% aller Betroffenen erreicht werden, wobei Selektionsverzerrungen zu diskutieren sind. Es ist anzunehmen, dass Personen, die nicht mit dem Internet vertraut sind, selten bis gar nicht teilgenommen haben. Hier könnten Gehörlose mit hohem Alter sowie möglicherweise mit niedriger Schreib- und Lesekompetenz besonders betroffen sein. Eine Prüfung auf Repräsentativität war jedoch nicht möglich, da die Grundgesamtheit der Gehörlosen mit sozioökonomischen Eckdaten nicht bekannt ist. Die dargestellten Ergebnisse weisen erstmalig bei einem großen Studienkollektiv Problembereiche in der medizinischen Versorgung von Gehörlosen in Deutschland auf: Gehörlose Patienten laufen Gefahr, ihren Arztbesuch durch vielfältige Kommunikationsbarrieren und Missverständnisse als Zumutung zu erleben. Eine Informationskampagne unter Ärzten könnte helfen, diese Situation zu verbessern. Dolmetscher können die Kommunikation zwischen Arzt und Patient enorm verbessern, die gesetzlich geregelte Kostenübernahme funktioniert dabei in der Regel auch problemlos. Allerdings gibt es noch viele Gehörlose, die nicht über die Regelungen zur Dolmetscherunterstützung informiert sind und die Dienste entsprechend nicht nutzen können. Hier muss es weitere Bemühungen geben, die Gehörlosen aufzuklären, um ihnen eine barrierefreie Nutzung von gesundheitsbezogenen Leistungen zu ermöglichen.

Factorization and non-local 1/m b corrections in the decay B X s gamma

In this thesis, a systematic analysis of the bar B to X_sgamma photon spectrum in the endpoint region is presented. The endpoint region refers to a kinematic configuration of the final state, in which the photon has a large energy m_b-2E_gamma = O(Lambda_QCD), while the jet has a large energy but small invariant mass. Using methods of soft-collinear effective theory and heavy-quark effective theory, it is shown that the spectrum can be factorized into hard, jet, and soft functions, each encoding the dynamics at a certain scale. The relevant scales in the endpoint region are the heavy-quark mass m_b, the hadronic energy scale Lambda_QCD and an intermediate scale sqrt{Lambda_QCD m_b} associated with the invariant mass of the jet. It is found that the factorization formula contains two different types of contributions, distinguishable by the space-time structure of the underlying diagrams. On the one hand, there are the direct photon contributions which correspond to diagrams with the photon emitted directly from the weak vertex. The resolved photon contributions on the other hand arise at O(1/m_b) whenever the photon couples to light partons. In this work, these contributions will be explicitly defined in terms of convolutions of jet functions with subleading shape functions. While the direct photon contributions can be expressed in terms of a local operator product expansion, when the photon spectrum is integrated over a range larger than the endpoint region, the resolved photon contributions always remain non-local. Thus, they are responsible for a non-perturbative uncertainty on the partonic predictions. In this thesis, the effect of these uncertainties is estimated in two different phenomenological contexts. First, the hadronic uncertainties in the bar B to X_sgamma branching fraction, defined with a cut E_gamma > 1.6 GeV are discussed. It is found, that the resolved photon contributions give rise to an irreducible theory uncertainty of approximately 5 %. As a second application of the formalism, the influence of the long-distance effects on the direct CP asymmetry will be considered. It will be shown that these effects are dominant in the Standard Model and that a range of -0.6 < A_CP^SM < 2.8 % is possible for the asymmetry, if resolved photon contributions are taken into account.

Risk factors promoting hypertensive crises: evidence from a longitudinal study

Background Current knowledge about risk factors promoting hypertensive crisis originates from retrospective data. Therefore, potential risk factors of hypertensive crisis were assessed in a prospective longitudinal study. Methods Eighty-nine patients of the medical outpatient unit at the University Hospital of Bern (Bern, Switzerland) with previously diagnosed hypertension participated in this study. At baseline, 33 potential risk factors were assessed. All patients were followed-up for the outcome of hypertensive crisis. Cox regression models were used to detect relationships between risk factors and hypertensive crisis (defined as acute rise of systolic blood pressure (BP) ≥200mmHg and/or diastolic BP ≥120mmHg). Results The mean duration of follow-up was 1.6 ± 0.3 years (range 1.0–2.4 years). Four patients (4.5%) were lost to follow-up. Thirteen patients (15.3%) experienced hypertensive crisis during follow-up. Several potential risk factors were significantly associated with hypertensive crisis: female sex, higher grades of obesity, the presence of a hypertensive or coronary heart disease, the presence of a somatoform disorder, a higher number of antihypertensive drugs, and nonadherence to medication. As measured by the hazard ratio, nonadherence was the most important factor associated with hypertensive crisis (hazard ratio 5.88, 95% confidence interval 1.59–21.77, P < 0.01). Conclusions This study identified several potential risk factors of hypertensive crisis. Results of this study are consistent with the hypothesis that improvement of medical adherence in antihypertensive therapy would help to prevent hypertensive crises. However, larger studies are needed to assess potential confounding, other risk factors and the possibility of interaction between predictors.

Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Design Network meta-analysis. Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

Interleukin-6, -7, -8 and -10 predict outcome in acute myocardial infarction complicated by cardiogenic shock

The IABP-SHOCK-trial was a morbidity-based randomized controlled trial in patients with infarction-related cardiogenic shock (CS), which used the change of the quantified degree of multiorgan failure as determined by APACHE II score over a 4-day period as primary outcome measure. The prospective hypothesis was that adding IABP therapy to "standard care" would improve CS-triggered multi organ dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with IABP support. In an inflammatory marker substudy, we analysed the prognostic value of interleukin (IL)-1β, -6, -7, -8, and -10 in patients with acute myocardial infarction complicated by cardiogenic shock.

Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance

The identification of associations between interleukin-28B (IL-28B) variants and the spontaneous clearance of hepatitis C virus (HCV) raises the issues of causality and the net contribution of host genetics to the trait. To estimate more precisely the net effect of IL-28B genetic variation on HCV clearance, we optimized genotyping and compared the host contributions in multiple- and single-source cohorts to control for viral and demographic effects. The analysis included individuals with chronic or spontaneously cleared HCV infections from a multiple-source cohort (n = 389) and a single-source cohort (n = 71). We performed detailed genotyping in the coding region of IL-28B and searched for copy number variations to identify the genetic variant or haplotype carrying the strongest association with viral clearance. This analysis was used to compare the effects of IL-28B variation in the two cohorts. Haplotypes characterized by carriage of the major alleles at IL-28B single-nucleotide polymorphisms (SNPs) were highly overrepresented in individuals with spontaneous clearance versus those with chronic HCV infections (66.1% versus 38.6%, P = 6 × 10(-9) ). The odds ratios for clearance were 2.1 [95% confidence interval (CI) = 1.6-3.0] and 3.9 (95% CI = 1.5-10.2) in the multiple- and single-source cohorts, respectively. Protective haplotypes were in perfect linkage (r(2) = 1.0) with a nonsynonymous coding variant (rs8103142). Copy number variants were not detected. CONCLUSION: We identified IL-28B haplotypes highly predictive of spontaneous HCV clearance. The high linkage disequilibrium between IL-28B SNPs indicates that association studies need to be complemented by functional experiments to identify single causal variants. The point estimate for the genetic effect was higher in the single-source cohort, which was used to effectively control for viral diversity, sex, and coinfections and, therefore, offered a precise estimate of the net host genetic contribution.

Analysis of 3D Soft Tissue Changes After 1- and 2-Jaw Orthognathic Surgery in Mandibular Prognathism Patients

Purpose Orthognathic surgery has the objective of altering facial balance to achieve esthetic results in patients who have severe disharmony of the jaws. The purpose was to quantify the soft tissue changes after orthognathic surgery, as well as to assess the differences in 3D soft tissue changes in the middle and lower third of the face between the 1- and 2-jaw surgery groups, in mandibular prognathism patients. Materials and Methods We assessed soft tissue changes of patients who have been diagnosed with mandibular prognathism and received either isolated mandibular surgery or bimaxillary surgery. The quantitative surface displacement was assessed by superimposing preoperative and postoperative volumetric images. An observer measured a surface-distance value that is shown as a contour line. Differences between the groups were determined by the Mann-Whitney U test. The Spearman correlation coefficient was used to evaluate a potential correlation between patients' surgical and cephalometric variables and soft tissue changes after orthognathic surgery in each group. Results There were significant differences in the middle third of the face between the 1- and 2-jaw surgery groups. Soft tissues in the lower third of the face changed in both surgery groups, but not significantly. The correlation patterns were more evident in the lower third of the face. Conclusion The overall soft tissue changes of the midfacial area were more evident in the 2-jaw surgery group. In 2-jaw surgery, significant changes would be expected in the midfacial area, but caution should be exercised in patients who have a wide alar base.