Assessment of the stereoselective fungal biotransformation of albendazole and its analysis by HPLC in polar organic mode

A high-performance liquid chromatographic method using polar organic mode was developed to analyze albendazole (ABZ), albendazole sulfone (ABZSO(2)) and the chiral and active metabolite albendazole sulfoxide (ABZSOX, ricobendazole) that was further applied in stereoselective fungal biotransformation studies. The chromatographic separation was performed on a Chiralpak AS column using acetonitrile:ethanol (97:3, v/v) plus 0.2% triethylamine and 0.2% acetic acid as the mobile phase at a flow rate of 0.5 mL min(-1). The present study employed hollow fiber liquid-phase microextraction as sample preparation. The method showed to be linear over the concentration range of 25-5000 ng mL(-1) for each ABZSOX enantiomer, 200-10,000 ng mL(-1) for ABZ and 50-1000 ng mL(-1) for ABZSO(2) metabolite with correlation coefficient (r)> 0.9934. The mean recoveries for ABZ, rac-ABZSOX and ABZSO(2) were, respectively, 9%, 33% and 20% with relative standard deviation below 10%. Within-day and between-day precision and accuracy assays for these analytes were studied at three concentration levels and were lower than 15%. This study opens the door regarding the possibility of using fungi in obtaining of the active metabolite ricobendazole. Nigrospora sphaerica (Sacc.) E. W. Mason (5567), Pestalotiopsis foedans (VR8), Papulaspora immersa Hotson (SS13) and Mucor rouxii were able to stereoselectively metabolize ABZ into its chiral metabolite. Among them, the fungus Mucor rouxii was the most efficient in the production of (+)-ABZSOX. (C) 2011 Elsevier B.V. All rights reserved.

Optimal Timing for Assessment of Tumor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer: Do All Patients Benefit From Waiting Longer Than 6 Weeks?

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([18 FDG] PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied (ClinicalTrials. org identifier NCT00254683). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks fromCRT completion). Clinical assessment was at 12 weeks. Maximal standard uptakevalue (SUVmax) of the primary tumor wasmeasured and recorded at eachPET/CTstudy after 1 h (early) and3 h (late) from 18 FDGinjection. Patientswith an increase in early SUVmax between 6 and 12 weeks were considered " bad" responders and the others as "good" responders. Results: Ninety-one patients were included; 46 patients (51%) were "bad" responders, whereas 45 (49%) patients were " good" responders. " Bad" responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; PZ. 001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; PZ. 008) and exhibited greater final tumor dimension (4.3cmvs. 3.3cm; PZ. 03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CTwas a significant predictor of " good" response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients. (C) 2012 Elsevier Inc.

Quantitative coronary arterial stenosis assessment by multidetector CT and invasive coronary angiography for identifying patients with myocardial perfusion abnormalities

Semi-quantitative stenosis assessment by coronary CT angiography only modestly predicts stress-induced myocardial perfusion abnormalities. The performance of quantitative CT angiography (QCTA) for identifying patients with myocardial perfusion defects remains unclear. CorE-64 is a multicenter, international study to assess the accuracy of 64-slice QCTA for detecting a parts per thousand yen50% coronary arterial stenoses by quantitative coronary angiography (QCA). Patients referred for cardiac catheterization with suspected or known coronary artery disease were enrolled. Area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the most severe coronary artery stenosis in a subset of 63 patients assessed by QCTA and QCA for detecting myocardial perfusion abnormalities on exercise or pharmacologic stress SPECT. Diagnostic accuracy of QCTA for identifying patients with myocardial perfusion abnormalities by SPECT revealed an AUC of 0.71, compared to 0.72 by QCA (P = .75). AUC did not improve after excluding studies with fixed myocardial perfusion abnormalities and total coronary arterial occlusions. Optimal stenosis threshold for QCTA was 43% yielding a sensitivity of 0.81 and specificity of 0.50, respectively, compared to 0.75 and 0.69 by QCA at a threshold of 59%. Sensitivity and specificity of QCTA to identify patients with both obstructive lesions and myocardial perfusion defects were 0.94 and 0.77, respectively. Coronary artery stenosis assessment by QCTA or QCA only modestly predicts the presence and the absence of myocardial perfusion abnormalities by SPECT. Confounding variables affecting the relationship between coronary anatomy and myocardial perfusion likely account for some of the observed discrepancies between coronary angiography and SPECT results.

Short Assessment of Health Literacy for Portuguese-Speaking Adults

OBJECTIVE: To develop and validate a short health literacy assessment tool for Portuguese-speaking adults. METHODS: The Short Assessment of Health Literacy for Portuguese-speaking Adults is an assessment tool which consists of 50 items that assess an individual's ability to correctly pronounce and understand common medical terms. We evaluated the instrument's psychometric properties in a convenience sample of 226 Brazilian older adults. Construct validity was assessed by correlating the tool scores with years of schooling, self-reported literacy, and global cognitive functioning. Discrimination validity was assessed by testing the tool's accuracy in detecting inadequate health literacy, defined as failure to fully understand standard medical prescriptions. RESULTS: Moderate to high correlations were found in the assessment of construct validity (Spearman's coefficients ranging from 0.63 to 0.76). The instrument showed adequate internal consistency (Cronbach's alpha=0.93) and adequate test-retest reliability (intraclass correlation coefficient=0.95). The area under the receiver operating characteristic curve for detection of inadequate health literacy was 0.82. A version consisting of 18 items was tested and showed similar psychometric properties. CONCLUSIONS: The instrument developed showed good validity and reliability in a sample of Brazilian older adults. It can be used in research and clinical settings for screening inadequate health literacy.

Assessment of using digital manipulation tools for diagnosing mandibular radiolucent lesions

Objective: The purpose of this study was to analyse the use of digital tools for image enhancement of mandibular radiolucent lesions and the effects of this manipulation on the percentage of correct radiographic diagnoses. Methods: 24 panoramic radiographs exhibiting radiolucent lesions were selected, digitized and evaluated by non-experts (undergraduate and newly graduated practitioners) and by professional experts in oral diagnosis. The percentages of correct and incorrect diagnoses, according to the use of brightness/contrast, sharpness, inversion, highlight and zoom tools, were compared. All dental professionals made their evaluations without (T-1) and with (T-2) a list of radiographic diagnostic parameters. Results: Digital tools were used with low frequency mainly in T-2. The most preferred tool was sharpness (45.2%). In the expert group, the percentage of correct diagnoses did not change when any of the digital tools were used. For the non-expert group, there was an increase in the frequency of correct diagnoses when brightness/contrast was used in T-2 (p = 0.008) and when brightness/contrast and sharpness were not used in T-1 (p = 0.027). The use or non-use of brightness/contrast, zoom and sharpness showed moderate agreement in the group of experts [kappa agreement coefficient (kappa) = 0.514, 0.425 and 0.335, respectively]. For the non-expert group there was slight agreement for all the tools used (kappa <= 0.237). Conclusions: Consulting the list of radiographic parameters before image manipulation reduced the frequency of tool use in both groups of examiners. Consulting the radiographic parameters with the use of some digital tools was important for improving correct diagnosis only in the group of non-expert examiners. Dentomaxillofacial Radiology (2012) 41, 203-210. doi: 10.1259/dmfr/78567773

Evaluation of Pain and Accuracy Diagnostic in Hospitalized Children

PURPOSE: Acute pain occurs in over 50% of hospitalized children. The accuracy of this diagnosis has been underexplored in the literature, as has the role of training to implement pain assessment. This study analyzed the accuracy of acute pain diagnoses after the implementation of a systematic evaluation of pain (study intervention). METHOD: The sample was divided into: pre- and postintervention. The Nursing Diagnosis Accuracy Scale, which scores accuracy as null, low, moderate, or high, was used. RESULTS: In the postimplementation, acute pain was diagnosed more often. However, accuracy only improved in the moderate category. CONCLUSION: Diagnosis of acute pain increased in the postimplementation period, but accuracy did not. IMPLICATIONS: The development of strategies for improvement of diagnostic accuracy is warranted.

Short Assessment of Health Literacy for Portuguese-speaking Adults

OBJECTIVE: To develop and validate a short health literacy assessment tool for Portuguese-speaking adults. METHODS: The Short Assessment of Health Literacy for Portuguese-speaking Adults is an assessment tool which consists of 50 items that assess an individual's ability to correctly pronounce and understand common medical terms. We evaluated the instrument's psychometric properties in a convenience sample of 226 Brazilian older adults. Construct validity was assessed by correlating the tool scores with years of schooling, self-reported literacy, and global cognitive functioning. Discrimination validity was assessed by testing the tool's accuracy in detecting inadequate health literacy, defined as failure to fully understand standard medical prescriptions. RESULTS: Moderate to high correlations were found in the assessment of construct validity (Spearman's coefficients ranging from 0.63 to 0.76). The instrument showed adequate internal consistency (Cronbach's alpha=0.93) and adequate test-retest reliability (intraclass correlation coefficient=0.95). The area under the receiver operating characteristic curve for detection of inadequate health literacy was 0.82. A version consisting of 18 items was tested and showed similar psychometric properties. CONCLUSIONS: The instrument developed showed good validity and reliability in a sample of Brazilian older adults. It can be used in research and clinical settings for screening inadequate health literacy.

Bovine Teeth in Age Assessment, from Medieval Cattle to Belgian Blue : Methodology, Possibilities and Limitations

The overall aim of the present thesis was to develop and characterise an age assessment method based on incremental lines in dental cementum using contemporary bovine teeth and teeth from archaeological faunal assemblages. The investigations also included two other age assessment methods: tooth wear pattern and macroscopic dental measurements. The first permanent mandibular molar and lower jaws from 70 contemporary cattle of known age and 170 archaeological molar sets from ten different Swedish archaeological sites were used. The following conclusions were drawn: • The number of incremental lines in the dental cementum varied between different parts of the tooth root as well as within one and the same individual. The results from contemporary cattle of known age showed a strong relationship between age and incremental lines in the cementum of the distal part of the mesial root (R2=65.5%) and the known ages of the animals. • With the “best” model variation in age could be explained to 65.5% (R2) by the number of incremental lines. Thus, the remaining age variation (approximately 35%) could not be explained by these lines. Other factors than must thus be responsible. However, with the exception of calves born the present material did not reveal any such significant relationship. • The results from cattle of known age indicate that the method of assessing age on the basis of cemental incremental lines is more reliable than other methods such as tooth wear or tooth measurements. However, by combining counting incremental lines and one variable assessing tooth dimension (tooth height) a slightly stronger relationship could be obtained (R2=74.5%). The results from age assessment of the medieval and post-Reformation cattle emphasize the importance of supplementing any age estimation of archaeological assemblages based on dental indicators with characteristics for the particular assessment model. Furthermore, conclusions based on age assessment with such models can not be drawn with any more detailed time scale than about 2 years leaving at best only 25% (R2) of factors influencing the dental indicator(s) utilized in the model unexplained. The accuracy of the age assessment required by the particular historical context in which the archaeological remains are found should thus decide what level of accuracy should be chosen.

Towards Rapid Environmental Assessment and Coastal Forecasting in the Northern Adriatic Sea

A new Coastal Rapid Environmental Assessment (CREA) strategy has been developed and successfully applied to the Northern Adriatic Sea. CREA strategy exploits the recent advent of operational oceanography to establish a CREA system based on an operational regional forecasting system and coastal monitoring networks of opportunity. The methodology wishes to initialize a coastal high resolution model, nested within the regional forecasting system, blending the large scale parent model fields with the available coastal observations to generate the requisite field estimates. CREA modeling system consists of a high resolution, O(800m), Adriatic SHELF model (ASHELF) implemented into the Northern Adriatic basin and nested within the Adriatic Forecasting System (AFS) (Oddo et al. 2006). The observational system is composed by the coastal networks established in the framework of ADRICOSM (ADRiatic sea integrated COastal areaS and river basin Managment system) Pilot Project. An assimilation technique exerts a correction of the initial field provided by AFS on the basis of the available observations. The blending of the two data sets has been carried out through a multi-scale optimal interpolation technique developed by Mariano and Brown (1992). Two CREA weekly exercises have been conducted: the first, at the beginning of May (spring experiment); the second in middle August (summer experiment). The weeks have been chosen looking at the availability of all coastal observations in the initialization day and one week later to validate model results, verifying our predictive skills. ASHELF spin up time has been investigated too, through a dedicated experiment, in order to obtain the maximum forecast accuracy within a minimum time. Energetic evaluations show that for the Northern Adriatic Sea and for the forcing applied, a spin-up period of one week allows ASHELF to generate new circulation features enabled by the increased resolution and its total kinetic energy to establish a new dynamical balance. CREA results, evaluated by mean of standard statistics between ASHELF and coastal CTDs, show improvement deriving from the initialization technique and a good model performance in the coastal areas of the Northern Adriatic basin, characterized by a shallow and wide continental shelf subject to substantial freshwater influence from rivers. Results demonstrate the feasibility of our CREA strategy to support coastal zone management and wish an additional establishment of operational coastal monitoring activities to advance it.

Quality assessment of a landslide inventory map and its application to land‐use planning. A case study in the Northern Apennines (Emilia‐Romagna region, Italy)

Landslide hazard and risk are growing as a consequence of climate change and demographic pressure. Land‐use planning represents a powerful tool to manage this socio‐economic problem and build sustainable and landslide resilient communities. Landslide inventory maps are a cornerstone of land‐use planning and, consequently, their quality assessment represents a burning issue. This work aimed to define the quality parameters of a landslide inventory and assess its spatial and temporal accuracy with regard to its possible applications to land‐use planning. In this sense, I proceeded according to a two‐steps approach. An overall assessment of the accuracy of data geographic positioning was performed on four case study sites located in the Italian Northern Apennines. The quantification of the overall spatial and temporal accuracy, instead, focused on the Dorgola Valley (Province of Reggio Emilia). The assessment of spatial accuracy involved a comparison between remotely sensed and field survey data, as well as an innovative fuzzylike analysis of a multi‐temporal landslide inventory map. Conversely, long‐ and short‐term landslide temporal persistence was appraised over a period of 60 years with the aid of 18 remotely sensed image sets. These results were eventually compared with the current Territorial Plan for Provincial Coordination (PTCP) of the Province of Reggio Emilia. The outcome of this work suggested that geomorphologically detected and mapped landslides are a significant approximation of a more complex reality. In order to convey to the end‐users this intrinsic uncertainty, a new form of cartographic representation is needed. In this sense, a fuzzy raster landslide map may be an option. With regard to land‐use planning, landslide inventory maps, if appropriately updated, confirmed to be essential decision‐support tools. This research, however, proved that their spatial and temporal uncertainty discourages any direct use as zoning maps, especially when zoning itself is associated to statutory or advisory regulations.

Assessment of gait spatio-temporal parameters in neurological disorders using wearable inertial sensors

Movement analysis carried out in laboratory settings is a powerful, but costly solution since it requires dedicated instrumentation, space and personnel. Recently, new technologies such as the magnetic and inertial measurement units (MIMU) are becoming widely accepted as tools for the assessment of human motion in clinical and research settings. They are relatively easy-to-use and potentially suitable for estimating gait kinematic features, including spatio-temporal parameters. The objective of this thesis regards the development and testing in clinical contexts of robust MIMUs based methods for assessing gait spatio-temporal parameters applicable across a number of different pathological gait patterns. First, considering the need of a solution the least obtrusive as possible, the validity of the single unit based approach was explored. A comparative evaluation of the performance of various methods reported in the literature for estimating gait temporal parameters using a single unit attached to the trunk first in normal gait and then in different pathological gait conditions was performed. Then, the second part of the research headed towards the development of new methods for estimating gait spatio-temporal parameters using shank worn MIMUs on different pathological subjects groups. In addition to the conventional gait parameters, new methods for estimating the changes of the direction of progression were explored. Finally, a new hardware solution and relevant methodology for estimating inter-feet distance during walking was proposed. Results of the technical validation of the proposed methods at different walking speeds and along different paths against a gold standard were reported and showed that the use of two MIMUs attached to the lower limbs associated with a robust method guarantee a much higher accuracy in determining gait spatio-temporal parameters. In conclusion, the proposed methods could be reliably applied to various abnormal gaits obtaining in some cases a comparable level of accuracy with respect to normal gait.

Assessment of the population structure and temporal changes in spatial dynamics and genetic characteristics of the Atlantic bluefin tuna under a fishery independent framework.

As a large and long-lived species with high economic value, restricted spawning areas and short spawning periods, the Atlantic bluefin tuna (BFT; Thunnus thynnus) is particularly susceptible to over-exploitation. Although BFT have been targeted by fisheries in the Mediterranean Sea for thousands of years, it has only been in these last decades that the exploitation rate has reached far beyond sustainable levels. An understanding of the population structure, spatial dynamics, exploitation rates and the environmental variables that affect BFT is crucial for the conservation of the species. The aims of this PhD project were 1) to assess the accuracy of larval identification methods, 2) determine the genetic structure of modern BFT populations, 3) assess the self-recruitment rate in the Gulf of Mexico and Mediterranean spawning areas, 4) estimate the immigration rate of BFT to feeding aggregations from the various spawning areas, and 5) develop tools capable of investigating the temporal stability of population structuring in the Mediterranean Sea. Several weaknesses in modern morphology-based taxonomy including demographic decline of expert taxonomists, flawed identification keys, reluctance of the taxonomic community to embrace advances in digital communications and a general scarcity of modern user-friendly materials are reviewed. Barcoding of scombrid larvae revealed important differences in the accuracy of the taxonomic identifications carried out by different ichthyoplanktologists following morphology-based methods. Using a Genotyping-by-Sequencing a panel of 95 SNPs was developed and used to characterize the population structuring of BFT and composition of adult feeding aggregations. Using novel molecular techniques, DNA was extracted from bluefin tuna vertebrae excavated from late iron age, ancient roman settlements Byzantine-era Constantinople and a 20th century collection. A second panel of 96 SNPs was developed to genotype historical and modern samples in order to elucidate changes in population structuring and allele frequencies of loci associated with selective traits.

The role of paved surfaces in the Urban Heat Island phenomenon: Assessment of fundamental thermal parameters and finite element analysis for UHI mitigation

Nowadays the environmental issues and the climatic change play fundamental roles in the design of urban spaces. Our cities are growing in size, many times only following immediate needs without a long-term vision. Consequently, the sustainable development has become not only an ethical but also a strategic need: we can no longer afford an uncontrolled urban expansion. One serious effect of the territory industrialisation process is the increase of urban air and surfaces temperatures compared to the outlying rural surroundings. This difference in temperature is what constitutes an urban heat island (UHI). The purpose of this study is to provide a clarification on the role of urban surfacing materials in the thermal dynamics of an urban space, resulting in useful indications and advices in mitigating UHI. With this aim, 4 coloured concrete bricks were tested, measuring their emissivity and building up their heat release curves using infrared thermography. Two emissivity evaluation procedures were carried out and subsequently put in comparison. Samples performances were assessed, and the influence of the colour on the thermal behaviour was investigated. In addition, some external pavements were analysed. Albedo and emissivity parameters were evaluated in order to understand their thermal behaviour in different conditions. Surfaces temperatures were recorded in a one-day measurements campaign. ENVI-met software was used to simulate how the tested materials would behave in two typical urban scenarios: a urban canyon and a urban heat basin. Improvements they can carry to the urban microclimate were investigated. Emissivities obtained for the bricks ranged between 0.92 and 0.97, suggesting a limited influence of the colour on this parameter. Nonetheless, white concrete brick showed the best thermal performance, whilst the black one the worst; red and yellow ones performed pretty identical intermediate trends. De facto, colours affected the overall thermal behaviour. Emissivity parameter was measured in the outdoor work, getting (as expected) high values for the asphalts. Albedo measurements, conducted with a sunshine pyranometer, proved the improving effect given by the yellow paint in terms of solar reflection, and the bad influence of haze on the measurement accuracy. ENVI-met simulations gave a demonstration on the effectiveness in thermal improving of some tested materials. In particular, results showed good performances for white bricks and granite in the heat basin scenario, and painted concrete and macadam in the urban canyon scenario. These materials can be considered valuable solutions in UHI mitigation.

A novel marker for heart failure: Cross sectional area assessment in a large vein by conductance catheter.

The present study investigates the feasibility of a new application able to check the heart failure status in a patient through the estimation of the venous distension. In this way it would be possible to follow up patients, avoiding invasive or expensive exams such as cardiac catheterization and echocardiography. Moreover, the devices would also be able to diagnose the decline of the disease, in order to allow a new adaptation to therapy, and vice versa to check the improvement in the patient’s conditions after the CRT device implant. This thesis is essentially divided into three parts: an analytical model was used to obtain an estimation of the error committed for the calculation of the CSA and to understand how the accuracy and sensitivity depend on the different configurations of the electrodes and the catheter position inside the vein; secondly, an in-vitro experiment was carried out in order to verify the practical feasibility for these kinds of measurements, in a very simplified model; in the end, several animal experiments were done to test the in-vivo practicability of the proposed method. The obtained results showed the feasibility of this approach. In fact, the error committed in the estimation of CSA, during the animal experiments, can be considered acceptable (CSAerror_max ≈ -14%). Moreover, it has been demonstrated that the conductance catheter allows assessing, not only the vein CSA, but also the breathing of the animal.

Evaluation of the new Statscan radiography device for ventriculoperitoneal shunt assessment

We assessed the diagnostic accuracy and time effectiveness of the Statscan low-dose full-body digital x-ray machine in the evaluation of ventriculoperitoneal (VP) shunt dysfunction.