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Over the last years two factors have deeply affected research in Manufacturing: the growing interest around Additive Manufacturing (AM) processes and the need to reduce the anthropogenic environmental impact. As result, a large papers concerning the environmental impact performance of AM compared to conventional processes have been published. Specifically, very complex models accounting for the impact of each life cycle stage of AMed components have been released. Results revealed that AM, at present, guarantees energy savings only within some domains, and the potential saving depends on several factors: product complexity, eco-properties of the material, energy intensity of the material deposition, light-weighting enabled by AM approaches and extent of the use phase. Above all, the result of the comparative analysis depends both on the considered factors and on the selected system boundaries. The already proposed models are very complex and many inventory data are needed, this could make them unapplicable at industrial level. In the presented paper, simplified models are proposed and the performances of these are quantified with varying the analyzed scenario (considered factors and selected system boundary). Results revealed that, for given scenarios, simplified models characterized by low computational effort, can provide reliable results. Guidelines for the implementation of different models with varying the system boundary are provided for the cumulative energy comparison of Electron Beam Melting and conventional turning for the production of titanium alloys components.

AbstractEqualizing opportunities for students to learn science and engineering in the ways described in the Next Generation Science Standards (NGSS) requires intentional planning. In this paper, we describe a framework for designing equitable and inclusive science lessons. We then share an example of how this framework was applied to the launch of a fifth-grade science unit, specifying the instructional strategies used to provide students with a meaningful, relevant, and engaging learning experience.

Advances in underwater camera technology provide an affordable means to quantify the environmental conditions under which fish spawn. This information is important for investigating spawning ecology, managing habitat, or providing information for captive breeding programs. We deployed 12 modified security cameras underwater to identify environmental conditions related to the spawning behavior of the critically endangered Moapa Dace Moapa coriacea, a Mojave Desert stream‐dwelling cyprinid that had never been observed spawning and that had fallen to a low of 459 individual fish 4 years prior to this study. Camera sites were selected systematically along the stream to represent the variety of conditions available. We divided the field of view in front of each camera into a grid, and we estimated both the available environment and the habitat over which Moapa Dace showed spawning behavior. From over 4,000 10‐min video clips that were randomly selected for analysis, 13 spawning events were identified. Using nonparametric contingency table analyses, we found that Moapa Dace selected depths between 30 and 34 cm, water velocities between 0.11 and 0.17 m/s, cobble substrate, and overhead instream cover. Although the recorded sample size of spawning events was small (13), our sample represents a large proportion of events given that the world's entire population of Moapa Dace at the time was approximately 650 fish distributed over multiple kilometers of stream length. Environmental conditions identified by this study were replicated in laboratory facilities to successfully propagate Moapa Dace for the first time in captivity. These propagation methods are now used in a management setting by the Nevada Department of Wildlife to maintain a captive population of this rare fish. Camera methods can be effective in helping to identify spawning conditions where water clarity is sufficient.

Cobalt−nickel bimetallic nanoparticles were synthesized by changing the sequence of the chemical reduction of Co(II) and Ni(II) ions confined in the core of bis(2-ethylhexyl)phosphate 2, and Ni(DEHP)2. The reduction was carried out by mixing, sequentially or contemporaneously, fixed amounts of n-heptane solution of Co(DEHP)2and Ni(DEHP)2micelles with a solution of sodium borohydride in ethanol at a fixed (reductant)/(total metal) molar ratio. This procedure involves the rapid formation of surfactant-coated nanoparticles, indicated as Co/Ni (Co after Ni), Ni/Co (Ni after Co), and Co + Ni (simultaneous), followed by their slow separation as nanostructures embedded in a sodium bis(2-ethylhexyl)phosphate matrix. The resulting composites, together with those obtained by reducing the n-heptane solutions of pure Co(DEHP)2or Ni(DEHP)2, were characterized by XPS, EXAFS, WAXS, and SAXS. The data analysis confirms the presence of nanometer-sized surfactant-coated cobalt, nickel, and cobalt/nickel particles. As expected, the composition and internal structure of cobalt/nickel bimetallic nanoparticles are influenced by the preparation sequence as well as by the “chemical affinity” between the surfactant and the metal. However, some atomic-scale physicochemical processes play a subtle role in determining the structural features of bimetallic nanoparticles. Further effects due to the competition between nanoparticle growing process and surfactant adsorption at the nanoparticle surface were observed.

Self‐assembling of amphiphilic molecules under electrospray ionization (ESI) conditions is characterized by quite unexpected phenomenology. The noticeable differences with respect to the condensed phase are attributable to the absence of the surfactant‐solvent interactions, the presence of net charge in the aggregates, and the strong deviation from equilibrium conditions. Aiming to investigate the effects of the net charge on abundance and stability of supramolecular surfactant aggregates, positively and negatively charged aggregates of sodium bis(2‐ethylhexyl)sulfosuccinate (AOT) and sodium methane sulfonate (MetS), butane sulfonate (ButS) and octane sulfonate (OctS) have been studied by ESI mass spectrometry, energy resolved mass spectrometry and density functional theory calculations. The negatively charged aggregates are found to be less stable than their positive counterparts. The results are consistent with a self‐assembling pattern dominated by electrostatic interactions involving the counterions and head groups of the investigated amphiphilic compounds while the alkyl chains point outwards, protecting the aggregates from unlimited growth processes. Copyright © 2011 John Wiley & Sons, Ltd.

Introduction Toxicity is a major problem for patients undergoing intravesical therapy with Bacillus Calmette-Guérin (BCG) for the conservative management of intermediate or high-risk non-muscle invasive bladder cancer (NMI-BC). A prospective pilot trial was designed to evaluate the adoption of a single dose of prulifloxacin to prevent the toxicity of BCG. Treatment tolerability and its possible influence on BCG efficacy have been analyzed.Materials and Methods The study was designed to evaluate the action of prulifloxacin in patients with intermediate or high-risk NMI-BC, undergoing 6–week induction cycle of BCG. Main exclusion criteria were previous intravesical therapy, urinary infection and any other factor that could influence tolerability to BCG intravesical immunotherapy. The patients were randomized to receive BCG alone versus BCG plus prulifloxacin. BCG toxicity and local tolerability were evaluated by self-administered EORTC QLQ-BLS24 questionnaire, and BCG adverse events (AEs) were classified according a four-class classification. The toxicity and tolerability evaluations were performed at baseline, one week after every instillation and one week and one month after the last instillation. Cystoscopy and cytology were performed 3–monthly. Recurrence and progression were recorded.Results The study included 43 patients receiving 258 instillations of BCG. The patients were randomized to receive BCG alone (Arm A: 132 instillations in 22 patients) versus BCG plus prulifloxacin given as a single oral dose (600 mg) 6 hours after the instillation. An advantage in favor of prulifloxacin prophylaxis emerged, according to EORTC QLQ-BLS24, in overall incidence of nocturnal micturitions (56% vs 28.6%; p=0.001), insomnia (40% vs 14.3%; p=0.002), urgency (70% vs 42.6%; p=0.05), incontinence (44% vs 12.7%; p=0.01) and bothersome events due to intravesical therapy (84% vs 63.5%; p=0.02). Systemic class IIB and III adverse events occurred in only 14.2% and 3.5% of the patients, respectively. No class IV AE was detected. Due to the low incidence no statistically significant difference was evident between the two arms (p=0.6). Three patients of Arm B and 1 patient of Arm A interrupted the treatment, after the 3rd- 4thinstillation. Anti-tuberculosis therapy war required for 3 months in only one patient. Three and 2 instillations were postponed for one-(two) week(s) in Arm B and Arm A, respectively. Prulifloxacin, generally well tolerated, was withdrawn in one patient due to skin allergic reaction. Recurrence rate at a mean follow-up of 12 months did not significantly differ between the two arms.Conclusions Prulifloxacin decreases the incidence of local symptoms and improves the compliance to BCG intravesical therapy. Due to the low number of events, no evidence emerges in our study about its capability of preventing severe systemic toxicity, although it has proved effective in reducing local symptoms.

The formation and structural features of positively mono-charged aggregates of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and sodium methane—(MetS), butane—(ButS) and octane—(OctS) sulfonate molecules in the gas phase have been investigated by electrospray ionization mass spectrometry, energy-resolved mass spectrometry and density functional theory (DFT) calculations. The experimental results show that the center-of-mass collision energy required to dissociate 50% of these mono-charged aggregates scantly depends on the length of the alkyl chain as well as on the aggregation number. This, together with the large predominance of mono-charged species in the mass spectra, was rationalized in terms of an aggregation pattern mainly driven by the counter ions and head groups electrostatic interactions while minor effects were attributed to the steric hindrance caused by the size of the surfactant head group and alkyl chain. DFT calculations show that the most favored structural arrangement of these aggregates is always characterized by an internal polar core constituted by the sodium counter ions and surfactant head groups surrounded by an external layer composed by the surfactant alkyl chains.

Introduction Prostate biopsy is nowadays one of the most frequent diagnostic procedures in urology. The incidence of bacteraemia, bacteriuria and infective complications is higher after the transrectal procedure than after the transperineal one. A survey demonstrated that 98% of the urologists in USA use antibiotics to prevent infective complications. The transrectal prostate biopsy is the only diagnostic intervention procedure in urology for which an antibiotic prophylaxis is recommended, also for low-risk patients, by the guidelines of the European Association of Urology. If the perineal route is adopted, the antibiotic prophylaxis is recommended only in high-risk patients.Materials and Methods The patient should preferably receive an evacuative enema to achieve a rectal cleansing and to ameliorate the diagnostic accuracy of transrectal ultrasound. A survey in the US demonstrated that an evacuative enema with saline solution is adopted by more than 80% of urologists. Criteria for antibiotics choice. The majority of bacteraemias are transitory, asymptomatic and self-limiting. On the other side, bacteriuria can persist for several days. Antibiotics must achieve high drug concentrations not only in plasma and tissue but also in urine. Symptomatic infections are generally caused by E. Coli and less frequently by the Streptococcus faecalis. Nevertheless, other agents as Klebsiella and Chlostridium, although rare, might cause severe infections. Thus, prophylaxis needs antibiotics at large spectrum and a single agent may not be enough for high-risk patients. Risk determination and drug schedules. It is essential to point out the infective risk of the patient. The choice of the drug, the timing and schedule of antibiotic prophylaxis are still object of debate. Several randomized studies have been conducted with contradictory results.Results The antibiotic prophylaxis should be tailored according to patients’ infective risk and to the procedure adopted. It is able to reduce infections rate after transrectal biopsy below 5%. The adoption of periprostatic anesthesia and the number of cores can influence the incidence of infective complications. Commonly, one-three days oral administration of fluoroquinolone is adopted. A single-dose prophylaxis can be also used with favorable results. Tolerability and route of administration should be taken into account, and also costs should be considered.Conclusions Considering the low cost of antibiotics adopted as short-term prophylaxis and the high cost of the treatment of infective complications, it seems reasonable to provide antibiotics prophylaxis for all patients at high risk for infective complications and for all cases submitted to transrectal prostate biopsy.

Introduction Conservative management is not applicable to all T1G3 tumors. The appropriate treatment should minimize mortality while assuring reduced morbidity and good quality of life. Several attempts have been done to identify categories of T1G3 patients at higher risk. The role of biologic markers is unclear and the prognostic risk factors are mainly clinical. The proper time to abandon the conservative approach in favor of cystectomy is still object of debate.Objectives The aim of the present study is to assess the clinical tumor features showing a detrimental effect on survival, identify the clinical risk factors impacting survival in patients undergoing conservative management of T1G3 bladder tumor, and to analyze the prognostic role of recurrence.Methods The present analysis is extended to 236 patients with T1G3 bladder tumors treated by TUR plus intravesical therapy between 1976 and 2005. Patients with previous T1G3, Tis, more than 3 tumors or greater than 3cm were excluded. Urinary cytology was obtained within 30 days after TUR. Since 2000 re-TUR has been performed. A sequential combination of mitomycin-C (30mg/30ml) and epirubicin (50mg/50ml) was adopted in 106 patients (44.9%). BCG or other agents were given intravesically in 85 (36.0%) and 38 (16.1%) patients, respectively. Seven (3%) patients refused intravescical therapy. In the case of Ta-T1 recurrence, TUR and one year of adjuvant intravesical therapy were repeated. Patients went off study if Tis, T1G3 or T-category tumor over T1 were detected. Age, previous history, number of tumors, re-TUR, adjuvant therapy, recurrence and progression were considered for survival analysis.Results Tumors were primary in 177 (75.3%) and single in 144 (61.5%) cases. At a mean follow-up of 52 months (range: 3–246 months), 116 patients (49.2%) relapsed. The recurring tumor was T1 in 47 (40.5%) cases and T1G3 in 33 (28.4%). In 11 additional patients (9.5%) a Tis was detected. Twenty-five patients (10.6%) progressed and 15 patients (6.4%) underwent cystectomy. Median overall survival was 167 months. The 5-year progression-free survival rate was 87.8%. Thirty-two patients (13.6%) died, 22 (9.3%) for bladder cancer. A higher mortality was detected in recurrent (p= 0.002) and multiple (p=0.009) tumors undergoing conservative management. Survival was decreased by NMI recurrence (p<0.0001) and by progression (p=0.009). No statistical significant difference in survival was evident in relation to the grade and stage of the recurrent tumor.Conclusions Previous positive history and multiplicity are relevant risk factors for survival in patients affected by T1G3 NMI TCCB conservatively treated. Survival is decreased if conservative management is not given up at the time of NMI recurrence, independently from its grade and stage.

To promote multiculturalism among grade school students through drama education. Grade 3–6 students (N=665) from 6 targeted schools including lead-class students (n=158) representing each school. Elementary schools in Windsor-Essex County, Ontario, Canada. In this non-experimental design study, group discussions conducted with each lead class to explore students’ understanding of multiculturalism were developed into an interactive drama performance and performed for all grades 3–6 students in their respective schools. A follow-up drama workshop was offered to each lead class one week after the drama performance. All students completed a 7-item questionnaire before and after the drama performance and after the drama workshop. Pre-test and post-test data collected were analyzed using T-test and ANOVA to determine the effects of drama education on students’ attitudes toward multiculturalism. Statistical analysis at 0.05 significance level revealed that both the performance and the drama workshop heightened students’ awareness of racism, and instilled cultural respect through “talking with others”, “accepting others”, and “believing that they can make a difference” in multiculturalism promotion. Drama education was an effective experiential tool for promoting multiculturalism in a school setting. The key to promoting inter-racial harmony is to respect and accept individual differences and to broaden the social determinants of health by providing culture safety care. D’utiliser l’éducation de drame pour promouvoir le multiculturalisme parmi les étudiants d’écoles élémentaires. Des élèves du 3e aux 6eannées (N=665) venant de six écoles visées, incluant des étudiants (N=158) représentant des classes à la tête de chaque école. Des écoles élémentaires dans la comté de Windsor-Essex, Ontario, Canada. L’p ]Intervention: Des discussions sur le multiculturalisme menées avec chaque classe à la tête étaient dévelopées dans une performance dramatique exécutée aux étudiants des 3e aux 6eannées. La semaine suivante, un atelier de drame était offert à chaque classe à la tête. Les étudiants ont répondu à une questionnaire à sept questions avant et après la performance et après l’atelier. Des analyses avec le T-test et l’ANOVA ont déterminé les effets de l’éducation de drame sur les attitudes des étudiants envers le multiculturalisme. À significance de 0,05, les analyses statistiques ont révélé que la performance et l’atelier de drame ont amélioré la conscience des étudiants de la racisme, et inculqué un respect pour d’autres cultures en « parlant avec les autres, » « accepter les autres, » et « croyant qu’ils peuvent faire une différence » dans la promotion du multiculturalisme. La L’éducation de drame était éffectif pour promouvoir le multiculturalisme parmi les élèves élémentaires. Afin de réaliser l’harmonie raciale, il faut respecter les différences individuelles, et élargir les déterminants sociaux de la santé en fournissant le soin sensible aux différences culturelles.

A wide investigation of the solubilization of the water-soluble salt Yb(NO3)3in sodium bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles and AOT liquid crystals has been carried out. After saturation of water/AOT/organic solvent w/o microemulsions with pure Yb(NO3)3, the Yb(NO3)3/AOT composites were prepared by complete evaporation under vacuum of the volatile components (water and organic solvent) of the salt-containing microemulsions. It was observed that these composites can be totally dissolved in pure n-heptane or CCl4, allowing the solubilization of a noticeable amount of Yb(NO3)3in quite dry apolar media. By UV–vis–NIR, FT-IR, and 1H NMR spectroscopies, some information on the state of Yb(NO3)3within AOT reverse micelles were acquired, whereas by small angle X-ray scattering (SAXS), it has been ascertained that Yb(NO3)3is quite homogeneously distributed as very small clusters among the reverse micelles. An analysis of SAXS and wide-angle X-ray scattering spectra of Yb(NO3)3/AOT composites leads to the hypothesis that, also in these systems, Yb(NO3)3is dispersed in the surfactant matrix as very small clusters.A wide investigation of the solubilization of the water-soluble salt Yb(NO3)3in sodium bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles and AOT liquid crystals has been carried out. After saturation of water/AOT/organic solvent w/o microemulsions with pure Yb(NO3)3, the Yb(NO3)3/AOT composites were prepared by complete evaporation under vacuum of the volatile components (water and organic solvent) of the salt-containing microemulsions. It was observed that these composites can be totally dissolved in pure n-heptane or CCl4, allowing the solubilization of a noticeable amount of Yb(NO3)3in quite dry apolar media. By UV–vis–NIR, FT-IR, and 1H NMR spectroscopies, some information on the state of Yb(NO3)3within AOT reverse micelles were acquired, whereas by small angle X-ray scattering (SAXS), it has been ascertained that Yb(NO3)3is quite homogeneously distributed as very small clusters among the reverse micelles. An analysis of SAXS and wide-angle X-ray scattering spectra of Yb(NO3)3/AOT composites leads to the hypothesis that, also in these systems, Yb(NO3)3is dispersed in the surfactant matrix as very small clusters.

The self‐assembling of sodium bis (2‐ethylhexyl) sulfosuccinate (AOT) in gas phase has been investigated by electrospray ionization‐ and matrix‐assisted laser desorption/ionization mass spectrometry. Large surfactant clusters with an aggregation number close to that found in apolar media have been observed either as positive or negative ions. Moreover, the marked predominance of singly charged species as well as preliminary theoretical calculations strongly suggest an aggregate structure characterized by an internal hydrophilic core hosting the extra charge surrounded by an apolar shell constituted by the surfactant alkyl chains. This structure is similar to that of the more familiar reversed micelles formed when an appropriate surfactant is solubilized in apolar solvents. Finally, similar trends are observed independently either on the ionization technique or the polarity of the solvent used. This, together with the large dependence of the aggregation number on the flow rates, strongly indicates that self‐assembling of the surfactant molecules occurs during the evaporation step. Copyright © 2005 John Wiley & Sons, Ltd.

Il toposclassico del sogno premonitore rivivenel teatro tragico italiano del Rinascimento configurandosi come componente strutturale fondamentale, semanticamente pregnante, sulla quale diversi autori basano la sintassi drammatica dei loro testi. Attraverso l'analisi comparativa di cinque opere esemplari di quella stagione letteraria (la Sofonisbadi Trissino, l'Oraziadell'Aretino, l'Orbecchedi Giraldi Cinthio, la Canacedi Speroni e il Torrismondodi Tasso), questo studio cerca di dimostrare come la rinascita della lingua tragica italiana nel Cinquecento si fondi anche sul tentativo di raggiungere una comunicazione più pienamente transitiva fra testo e fruitori, chiamati ad avanzare, per tutta la durata della rappresentazione, possibili “scioglimenti” dei nodi drammatici. Il sogno costituisce non solo un sintomo della rinnovata attenzione verso le strutture immaginative dei testi, ma anche un canale privilegiato per questa comunicazione, un momento topico in cui si tocca quella zona “liminale” dell'esperire umano dove la ragione e la logica lasciano spazio ad altre dimensioni cognitive come l'intuito e le emozioni tragiche per eccellenza della “pietà” e dell‘“orrore.”

To study the ablative activity of intravescical gemcitabine against superficial transitional cell carcinoma of the bladder at different doses and concentrations.Methods Twenty-seven patients were treated with intravescical gemcitabine after transurethral resection, during which one to three papillary marker lesions were left unresected. Starting 14 days after transurethral resection, six gemcitabine instillations were given at weekly intervals. Gemcitabine, diluted in 50 mL of saline solution and maintained for 2 hr, was given at a dose of 500, 1000 and 2000 mg in groups of nine patients each. A complete response (CR) was defined as negative cutologycystoscopy and biopsy findings.Results Of the 27 patients, one was lost to follow-up, and of the remaining 26 patients, six (23%) achieved a CR. A CR was achieved in one patient (12.5%), in two patients (22.2%) and in three patients (33.3%) at dose of 500, 1000 and 2000 mg, respectively. A partial response was obtained in two additional patients (22%) at a dose of 500 and 1000 mg. Bladder Tis was diagnosed in two patients with a CR at 8 and 3 months, respectively. Systemic and local tolerability was excellent, and the interruption of treatment was not required.Conclusions Our experience has shown the good tolerability and the potential efficacy of intravescical gemcitabine against recurrent transitional cell carcinoma of the bladder. Gemcitabine could be proposed, if our results are confirmed by larger studies, as a second-line therapy in patients who cannot tolerate more aggressive intravescical therapy.

Cobalt–iron cyanide (Co x[Fe(CN) 6]) nanoparticles have been synthesized by a novel solid–solid reaction in the confined space of dry sodium bis(2-ethylhexyl)sulfosuccinate (AOT) reversed micelles dispersed in n-heptane. The reaction has been carried out by mixing two dry AOT/ n-heptane solutions containing CoCl 2 and K 4Fe(CN) 6 or K 3Fe(CN) 6 nanoparticles in the micellar core, respectively. By UV-Vis spectroscopy it was ascertained that, after the mixing process, the formation of stable nanoparticles is fast and complete. Microcalorimetric measurements of the thermal effect due to the Co x[Fe(CN) 6] nanoparticle formation allowed the determination of the stoichiometric ratio (x) and of the molar enthalpy of reaction in the core of AOT reversed micelles. The observed behavior suggests the occurrence of confinement effects and surfactant adsorption on the nanoparticle surface. Further structural information was achieved by small-angle X-ray scattering (SAXS) measurements. From all liquid samples, interesting salt/AOT composites were prepared by simple evaporation of the apolar solvent. Size, crystal structure, and electronic properties of Co x[Fe(CN) 6] nanoparticles containing composites were obtained by wide-angle X-ray scattering (WAXS) and X-ray photoelectron spectroscopy (XPS).

The state of acetamide nanoparticles encapsulated in the hydrophilic core of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reversed micelles and dispersed in CCl 4 has been investigated by Fourier transform infrared spectroscopy. The analysis of the vibrational spectra reveals even at the higher acetamide to AOT molar ratio some changes of the typical H-bonded structure of solid acetamide ascribable to their small size, confinement effects, and acetamide-AOT head group interactions. The stretching modes of acetamide CO and AOT sulfonate groups indicate unambiguously specific acetamide-AOT head group interactions.

The structure of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and that of urea containing AOT reversed micelles has been investigated by small-angle neutron scattering (SANS) and Fourier transform infrared (FT-IR) spectroscopy at different AOT concentrations and urea/AOT molar ratios. For the AOT/n-heptane system, SANS data analysis indicates that AOT molecules form prolate ellipsoidal aggregates, which grow asymmetrically along the major axis upon increasing the surfactant concentration. For the urea/AOT/n-heptane system, the SANS results are consistent with the hypothesis that urea is encapsulated as small-sized ellipsoidal hydrogen-bonded clusters within the hydrophilic micellar core of the AOT reversed micelles. The insertion of urea in the micellar core causes a significant increase of the aggregate size along the minor-axis direction. FT-IR data indicates that, quite independently from the urea and AOT concentrations, the encapsulation of urea clusters in the AOT micellar core involves some changes of the H-bonded structure characterizing pure solid urea. This structural change was rationalized in terms of the specific interactions between the urea NH2 and the AOT SO3^- groups in small-sized urea clusters. Moreover, the CO stretching mode analysis suggests that within the cluster the urea CO groups interact with the urea NH2 groups whereas the AOT CO groups do not.

The state of N-methylurea (NMU) confined within the hydrophilic core of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reversed micelles (radius 1.5–1.8 nm) has been investigated by Fourier transform infrared spectroscopy. The analysis of the spectral features leads to the hypothesis that NMU is encapsulated in the micellar core as small-sized molecular clusters. As a consequence of their small size and of NMU–AOT head group interactions, these clusters display marked departures from the H-bonded structure of the pure solid NMU even at the higher NMU to AOT molar ratio. The stretching modes of NMU CO, AOT CO and sulfonate groups indicate unambiguously specific NMU–AOT head group interactions.

A variance-stabilizing transformation (VST) was applied to the linear regression of calibration standards of different drugs in plasma. This transformation involved the normalization of the dependent variable peak height or peak area ratio (Y), and the independent variable, plasma drug concentration (C). This transformation led to a constant variance in the regression error term across the measured concentration range and allowed the evaluation of the unbiased slope and y intercept with minimum variance. The utility of the VST procedure in comparison with the ordinary least squares (OLS) approach, routinely used in pharmaceutical studies for constructing calibration lines, is described. The principal advantage of the VST approach is allowing a lower minimum level of drug quantification while using a single calibration line over a wide range of drug concentrations. The VST method is especially useful to quantify drug plasma levels in pharmacokinetic evaluation of sustainedrelease dosage forms, where the precise quantification of low levels of drug is critical. The application of the VST method was explored and evaluated in comparison with the OLS method for pharmacokinetic assays of diltiazem, gallopamil, nitroglycerin, and nicotine.

The FDA Cooperative Efficacy Study of transdermal nitroglycerin utilized a combination of marketed products over a wide dose range. Unfortunately, plasma nitroglycerin concentrations were not determined. The current study was conducted to assess plasma nitrate concentrations after transdermal doses of 15, 30, 60, and 105 mg/24 hr employing the FDA Cooperative Study design. Plasma concentrations of nitroglycerin, 1,3-glyceryl dinitrate, and 1,2-glyceryl dinitrate were determined during the 24 hr of application and for 1 hr after transdermal system removal. Dose proportionality was assessed after normalizing the data by theoretical dose. For nitroglycerin, dose-normalized AUC(0_8) and Cmax were higher for the 105 mg/24 hr dose than for the other doses. For the metabolites, 1,3-glyceryl dinitrate and 1,2-glyceryl dinitrate, there were no differences in dose-normalized AUC(0_8) and dose-normalized Cmax between the dose levels. No differences were seen in Tmax between the dose levels for all three species. Based on the dinitrate metabolites, dose proportionality was seen over the 15 to 105 mg/24 hr dose range. Nitroglycerin, however, was found to be linear only between 15 and 60 mg/24 hr.

The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro-Dur. Twenty-four healthy male volunteers completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24h after topical application of the units, and 30min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steadystate concentrations of nitroglycerin were 182 and 224pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 ± 4.11 and 10.67 ± 4.78mg, respectively, or ∼ 10mg in 24h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p=0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established.

Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.

Introduction The European guidelines classify primary bladder tumors of Ta category and G1–2 grade as low risk tumors when single or less than 7 in number and 3 cm in diameter. The aim of the present paper was to evaluate the usefulness of EORTC Risk Tables when applied to non-selected patients in daily clinical practice.Material and Methods In the present retrospective study 129 consecutive patients affected by primary bladder tumors category Ta and Grade G1–2 have been considered. The median follow-up was 48 months. Bladder tumors were TaG1 in 69 (53.5%) patients, TaG2 in 60 (46.5%), single in 82 (63.6%) and multiple in 47 (36.4%) cases. Fifty-one patients (39.5%) received adjuvant intravesical chemotherapy.Results At a median follow-up of 48 months, 70 (41.8%) patients recurred. Recurrence occurred in 43.5% of TaG1 versus 66.7% of TaG2 tumors (p=0.003), in 50% of single tumors versus 61.7% of multiple (p=0.096), in 41.2% of patients receiving adjuvant chemotherapy versus 62.8% of untreated patients (p=0.007). Progression to G3 grade, T1 category and muscle invasive tumor occurred in 3%, 10% and 2% of cases, respectively.Conclusions The EORTC Risk Tables can be applied in common clinical practice to unselected low-risk patients.

The efficacy and local toxicity of the intravesical combination of microwave-induced hyperthermia with a cytostatic agent in patients affected by superficial bladder cancer is presented. Between 1994 and 2002, two studies were performed on ablative and adjuvant intravesical thermo-chemotherapy. The ablative study demonstrated complete tumor eradication in 88% of patients who should have undergone cystectomy due to diffuse multiple papillary tumors non-responsive TUR and intravescical adjuvant therapy. In a randomized study, comparing adjuvant thermo-chemotherapy vs. standard chemotherapy with mitomycin C, recurrence-free survival analysis at 24 months revealed a significant difference in favor of thermo-chemotherapy. Our preliminary experience confirmed that local side effects, mainly cystitis, suprapubic pain and thermal reaction of the posterior bladder wall, were transitory and did not require treatment interruption.

Subclinical infections of the prostate can increase the prostate-specific antigen (PSA) values in patients with normal digital rectal examination. This study aimed to evaluate the role of short-term antimicrobial therapy in reducing the PSA value in patients as candidates for transrectal biopsy. Fifty-eight patients with negative digital rectal examination and PSA values between 4 and 20 ng/mL were included in the study. Antibiotics were administered to all patients for 3 weeks, and the PSA was reassessed 10 days after the end of the treatment. Patients were subsequently submitted to prostate biopsy.A reduction in PSA was detected in 34 patients (59%). Mean percentage reduction was 32%. In only six patients (10%) did the PSA return to normal levels. Prostate biopsy revealed prostate cancer in 26 patients (45%). Prostate cancer was not detected in patients with PSA levels above 4 ng/mL. Prostate biopsy can be avoided only in a small number of patients showing the normalization of PSA levels after short-term antimicrobial therapy. These patients should be strictly monitored with frequent PSA determinations.