Bifurcation analysis of an aeroelastic system with concentrated nonlinearities

Analytical and numerical analyses of the nonlinear response of a three-degree-of-freedom nonlinear aeroelastic system are performed. Particularly, the effects of concentrated structural nonlinearities on the different motions are determined. The concentrated nonlinearities are introduced in the pitch, plunge, and flap springs by adding cubic stiffness in each of them. Quasi-steady approximation and the Duhamel formulation are used to model the aerodynamic loads. Using the quasi-steady approach, we derive the normal form of the Hopf bifurcation associated with the system's instability. Using the nonlinear form, three configurations including supercritical and subcritical aeroelastic systems are defined and analyzed numerically. The characteristics of these different configurations in terms of stability and motions are evaluated. The usefulness of the two aerodynamic formulations in the prediction of the different motions beyond the bifurcation is discussed.

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP-EBMT analysis

To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) = 0.4, P = 0.01) and for those transplanted in CR1 and CR2 (HR = 0.3, P = 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P = 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR = 2, P = 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes. Leukemia (2012) 26, 2455-2461; doi:10.1038/leu.2012.123

Longitudinal familial analysis of blood pressure involving parametric (co)variance functions

Abstract Background For analyzing longitudinal familial data we adopted a log-linear form to incorporate heterogeneity in genetic variance components over the time, and additionally a serial correlation term in the genetic effects at different levels of ages. Due to the availability of multiple measures on the same individual, we permitted environmental correlations that may change across time. Results Systolic blood pressure from family members from the first and second cohort was used in the current analysis. Measures of subjects receiving hypertension treatment were set as censored values and they were corrected. An initial check of the variance and covariance functions proposed for analyzing longitudinal familial data, using empirical semi-variogram plots, indicated that the observed trait dispersion pattern follows the assumptions adopted. Conclusion The corrections for censored phenotypes based on ordinary linear models may be an appropriate simple model to correct the data, ensuring that the original variability in the data was retained. In addition, empirical semi-variogram plots are useful for diagnosis of the (co)variance model adopted.

Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria

Abstract Background The development of protective immunity against malaria is slow and to be maintained, it requires exposure to multiple antigenic variants of malaria parasites and age-associated maturation of the immune system. Evidence that the protective immunity is associated with different classes and subclasses of antibodies reveals the importance of considering the quality of the response. In this study, we have evaluated the humoral immune response against Plasmodium falciparum blood stages of individuals naturally exposed to malaria who live in endemic areas of Brazil in order to assess the prevalence of different specific isotypes and their association with different malaria clinical expressions. Methods Different isotypes against P. falciparum blood stages, IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgE and IgA, were determined by ELISA. The results were based on the analysis of different clinical expressions of malaria (complicated, uncomplicated and asymptomatic) and factors related to prior malaria exposure such as age and the number of previous clinical malaria attacks. The occurrence of the H131 polymorphism of the FcγIIA receptor was also investigated in part of the studied population. Results The highest levels of IgG, IgG1, IgG2 and IgG3 antibodies were observed in individuals with asymptomatic and uncomplicated malaria, while highest levels of IgG4, IgE and IgM antibodies were predominant among individuals with complicated malaria. Individuals reporting more than five previous clinical malaria attacks presented a predominance of IgG1, IgG2 and IgG3 antibodies, while IgM, IgA and IgE antibodies predominated among individuals reporting five or less previous clinical malaria attacks. Among individuals with uncomplicated and asymptomatic malaria, there was a predominance of high-avidity IgG, IgG1, IgG2 antibodies and low-avidity IgG3 antibodies. The H131 polymorphism was found in 44.4% of the individuals, and the highest IgG2 levels were observed among asymptomatic individuals with this allele, suggesting the protective role of IgG2 in this population. Conclusion Together, the results suggest a differential regulation in the anti-P. falciparum antibody pattern in different clinical expressions of malaria and showed that even in unstable transmission areas, protective immunity against malaria can be observed, when the appropriated antibodies are produced.

Physicochemical analysis of blood and urine in the course of acute kidney injury in critically ill patients: a prospective, observational study

Abstract Background Sequential physicochemical alterations in blood and urine in the course of acute kidney injury (AKI) development have not been previously described. We aimed to describe these alterations in parallel to traditional renal and acid–base parameters. Methods One hundred and sixty eight consecutive critically ill patients with no previous kidney disease, who had an indwelling urinary catheter at ICU admission and who remained with the catheter for at least two days without dialysis were included. A sample of blood and spot urine were collected simultaneously, once daily, until catheter removal or dialysis requirement. Traditional acid–base and renal parameters were sequentially evaluated in parallel to blood and urinary physicochemical parameters. Patients were classified during this period as having or not AKI and, for patients with AKI, duration (transient or persistent) and severity (creatinine-based AKIN stage) were evaluated. Results One hundred and thirteen patients (67.3%) had AKI: 92 at ICU admission and 21 during the observation period. AKI development was characterized in blood by increased values of phosphate and unmeasured anions (SIG), decreased albumin, and in urine by decreased values of sodium (NaU), chloride (ClU) as well as high urinary strong ion difference (SIDu). These alterations began to occur before AKI diagnosis, and they reverted in transient AKI but remained in persistent AKI. NaU, ClU and albumin decreased, and phosphate, SIG and SIDu increased with AKI severity progression. NaU and ClU values increased again when AKIN stage 3 was reached. Conclusions Simultaneous physicochemical analysis of blood and urine revealed standardized alterations that characterize AKI development in critically ill patients. These alterations paralleled AKI duration and severity. Future studies should consider including sequential evaluation of urine biochemistry as part of the armamentarium for AKI diagnosis and management.

Automated system of seedling image analysis (SVIS) and electrical conductivity to assess sun hemp seed vigor

The development of new procedures for quickly obtaining accurate information on the physiological potential of seed lots is essential for developing quality control programs for the seed industry. In this study, the effectiveness of an automated system of seedling image analysis (Seed Vigor Imaging System - SVIS) in determining the physiological potential of sun hemp seeds and its relationship with electrical conductivity tests, were evaluated. SVIS evaluations were performed three and four days after sowing and data on the vigor index and the length and uniformity of seedling growth were collected. The electrical conductivity test was made on 50 seed replicates placed in containers with 75 mL of deionised water at 25 ºC and readings were taken after 1, 2, 4, 8 and 16 hours of imbibition. Electrical conductivity measurements at 4 or 8 hours and the use of the SVIS on 3-day old seedlings can effectively detect differences in vigor between different sun hemp seed lots.

Performance of six diagnostic tests to screen for Chagas disease in blood banks and prevalence of Trypanosoma cruzi infection among donors with inconclusive serology screening based on the analysis of epidemiological variables

OBJECTIVE: The frequent occurrence of inconclusive serology in blood banks and the absence of a gold standard test for Chagas'disease led us to examine the efficacy of the blood culture test and five commercial tests (ELISA, IIF, HAI, c-ELISA, rec-ELISA) used in screening blood donors for Chagas disease, as well as to investigate the prevalence of Trypanosoma cruzi infection among donors with inconclusive serology screening in respect to some epidemiological variables. METHODS: To obtain estimates of interest we considered a Bayesian latent class model with inclusion of covariates from the logit link. RESULTS: A better performance was observed with some categories of epidemiological variables. In addition, all pairs of tests (excluding the blood culture test) presented as good alternatives for both screening (sensitivity > 99.96% in parallel testing) and for confirmation (specificity > 99.93% in serial testing) of Chagas disease. The prevalence of 13.30% observed in the stratum of donors with inconclusive serology, means that probably most of these are non-reactive serology. In addition, depending on the level of specific epidemiological variables, the absence of infection can be predicted with a probability of 100% in this group from the pairs of tests using parallel testing. CONCLUSION: The epidemiological variables can lead to improved test results and thus assist in the clarification of inconclusive serology screening results. Moreover, all combinations of pairs using the five commercial tests are good alternatives to confirm results.

Natural blood feeding and temperature shift modulate the global transcriptional profile of Rickettsia rickettsii infecting its tick vector

Rickettsia rickettsii is an obligate intracellular tick-borne bacterium that causes Rocky Mountain Spotted Fever (RMSF), the most lethal spotted fever rickettsiosis. When an infected starving tick begins blood feeding from a vertebrate host, R. rickettsii is exposed to a temperature elevation and to components in the blood meal. These two environmental stimuli have been previously associated with the reactivation of rickettsial virulence in ticks, but the factors responsible for this phenotype conversion have not been completely elucidated. Using customized oligonucleotide microarrays and high-throughput microfluidic qRT-PCR, we analyzed the effects of a 10 degrees C temperature elevation and of a blood meal on the transcriptional profile of R. rickettsii infecting the tick Amblyomma aureolatum. This is the first study of the transcriptome of a bacterium in the genus Rickettsia infecting a natural tick vector. Although both stimuli significantly increased bacterial load, blood feeding had a greater effect, modulating five-fold more genes than the temperature upshift. Certain components of the Type IV Secretion System (T4SS) were up-regulated by blood feeding. This suggests that this important bacterial transport system may be utilized to secrete effectors during the tick vector's blood meal. Blood feeding also up-regulated the expression of antioxidant enzymes, which might correspond to an attempt by R. rickettsii to protect itself against the deleterious effects of free radicals produced by fed ticks. The modulated genes identified in this study, including those encoding hypothetical proteins, require further functional analysis and may have potential as future targets for vaccine development.

Quantitative analysis of photodynamic therapy effects in rat mammary tumor vascular density using image-pro plus software

Photodynamic therapy (PDT) is a treatment modality that has advanced rapidly in recent years. It causes tissue and vascular damage with the interaction of a photosensitizing agent (PS), light of a proper wavelength, and molecular oxygen. Evaluation of vessel damage usually relies on histopathology evaluation. Results are often qualitative or at best semi-quantitative based on a subjective system. The aim of this study was to evaluate, using CD31 immunohistochem- istry and image analysis software, the vascular damage after PDT in a well-established rodent model of chemically induced mammary tumor. Fourteen Sprague-Dawley rats received a single dose of 7,12-dimethylbenz(a)anthraxcene (80 mg/kg by gavage), treatment efficacy was evaluated by comparing the vascular density of tumors after treatment with Photogem® as a PS, intraperitoneally, followed by interstitial fiber optic lighting, from a diode laser, at 200 mW/cm and light dose of 100 J/cm directed against his tumor (7 animals), with a control group (6 animals, no PDT). The animals were euthanized 30 hours after the lighting and mammary tumors were removed and samples from each lesion were formalin-fixed. Immunostained blood vessels were quantified by Image Pro-Plus version 7.0. The control group had an average of 3368.6 ± 4027.1 pixels per picture and the treated group had an average of 779 ± 1242.6 pixels per area (P < 0.01), indicating that PDT caused a significant decrease in vascular density of mammary tumors. The combined immu- nohistochemistry using CD31, with selection of representative areas by a trained pathology, followed by quantification of staining using Image Pro-Plus version 7.0 system was a practical and robust methodology for vessel damage evalua- tion, which probably could be used to assess other antiangiogenic treatments.

Multitemporal analysis of satellite imagery: implementation of a land evolution model in ALCS (ATSR LAND CLASSIFICATION SYSTEM)

In this report it was designed an innovative satellite-based monitoring approach applied on the Iraqi Marshlands to survey the extent and distribution of marshland re-flooding and assess the development of wetland vegetation cover. The study, conducted in collaboration with MEEO Srl , makes use of images collected from the sensor (A)ATSR onboard ESA ENVISAT Satellite to collect data at multi-temporal scales and an analysis was adopted to observe the evolution of marshland re-flooding. The methodology uses a multi-temporal pixel-based approach based on classification maps produced by the classification tool SOIL MAPPER ®. The catalogue of the classification maps is available as web service through the Service Support Environment Portal (SSE, supported by ESA). The inundation of the Iraqi marshlands, which has been continuous since April 2003, is characterized by a high degree of variability, ad-hoc interventions and uncertainty. Given the security constraints and vastness of the Iraqi marshlands, as well as cost-effectiveness considerations, satellite remote sensing was the only viable tool to observe the changes taking place on a continuous basis. The proposed system (ALCS – AATSR LAND CLASSIFICATION SYSTEM) avoids the direct use of the (A)ATSR images and foresees the application of LULCC evolution models directly to „stock‟ of classified maps. This approach is made possible by the availability of a 13 year classified image database, conceived and implemented in the CARD project (http://earth.esa.int/rtd/Projects/#CARD).The approach here presented evolves toward an innovative, efficient and fast method to exploit the potentiality of multi-temporal LULCC analysis of (A)ATSR images. The two main objectives of this work are both linked to a sort of assessment: the first is to assessing the ability of modeling with the web-application ALCS using image-based AATSR classified with SOIL MAPPER ® and the second is to evaluate the magnitude, the character and the extension of wetland rehabilitation.

A skin surface characterization system based on capacitive image analysis

During the last few years, several methods have been proposed in order to study and to evaluate characteristic properties of the human skin by using non-invasive approaches. Mostly, these methods cover aspects related to either dermatology, to analyze skin physiology and to evaluate the effectiveness of medical treatments in skin diseases, or dermocosmetics and cosmetic science to evaluate, for example, the effectiveness of anti-aging treatments. To these purposes a routine approach must be followed. Although very accurate and high resolution measurements can be achieved by using conventional methods, such as optical or mechanical profilometry for example, their use is quite limited primarily to the high cost of the instrumentation required, which in turn is usually cumbersome, highlighting some of the limitations for a routine based analysis. This thesis aims to investigate the feasibility of a noninvasive skin characterization system based on the analysis of capacitive images of the skin surface. The system relies on a CMOS portable capacitive device which gives 50 micron/pixel resolution capacitance map of the skin micro-relief. In order to extract characteristic features of the skin topography, image analysis techniques, such as watershed segmentation and wavelet analysis, have been used to detect the main structures of interest: wrinkles and plateau of the typical micro-relief pattern. In order to validate the method, the features extracted from a dataset of skin capacitive images acquired during dermatological examinations of a healthy group of volunteers have been compared with the age of the subjects involved, showing good correlation with the skin ageing effect. Detailed analysis of the output of the capacitive sensor compared with optical profilometry of silicone replica of the same skin area has revealed potentiality and some limitations of this technology. Also, applications to follow-up studies, as needed to objectively evaluate the effectiveness of treatments in a routine manner, are discussed.

Innovative analytical methods for Central Nervous System Drug analysis in biological fluids

During recent years a consistent number of central nervous system (CNS) drugs have been approved and introduced on the market for the treatment of many psychiatric and neurological disorders, including psychosis, depression, Parkinson disease and epilepsy. Despite the great advancements obtained in the treatment of CNS diseases/disorders, partial response to therapy or treatment failure are frequent, at least in part due to poor compliance, but also genetic variability in the metabolism of psychotropic agents or polypharmacy, which may lead to sub-therapeutic or toxic plasma levels of the drugs, and finally inefficacy of the treatment or adverse/toxic effects. With the aim of improving the treatment, reducing toxic/side effects and patient hospitalisation, Therapeutic Drug Monitoring (TDM) is certainly useful, allowing for a personalisation of the therapy. Reliable analytical methods are required to determine the plasma levels of psychotropic drugs, which are often present at low concentrations (tens or hundreds of nanograms per millilitre). The present PhD Thesis has focused on the development of analytical methods for the determination of CNS drugs in biological fluids, including antidepressants (sertraline and duloxetine), antipsychotics (aripiprazole), antiepileptics (vigabatrin and topiramate) and antiparkinsons (pramipexole). Innovative methods based on liquid chromatography or capillary electrophoresis coupled to diode-array or laser-induced fluorescence detectors have been developed, together with the suitable sample pre-treatment for interference removal and fluorescent labelling in case of LIF detection. All methods have been validated according to official guidelines and applied to the analysis of real samples obtained from patients, resulting suitable for the TDM of psychotropic drugs.

Development of human visual system analysis for the implementation of a new instrument for flicker measurement

Flicker is a power quality phenomenon that applies to cycle instability of light intensity resulting from supply voltage fluctuation, which, in turn can be caused by disturbances introduced during power generation, transmission or distribution. The standard EN 61000-4-15 which has been recently adopted also by the IEEE as IEEE Standard 1453 relies on the analysis of the supply voltage which is processed according to a suitable model of the lamp – human eye – brain chain. As for the lamp, an incandescent 60 W, 230 V, 50 Hz source is assumed. As far as the human eye – brain model is concerned, it is represented by the so-called flicker curve. Such a curve was determined several years ago by statistically analyzing the results of tests where people were subjected to flicker with different combinations of magnitude and frequency. The limitations of this standard approach to flicker evaluation are essentially two. First, the provided index of annoyance Pst can be related to an actual tiredness of the human visual system only if such an incandescent lamp is used. Moreover, the implemented response to flicker is “subjective” given that it relies on the people answers about their feelings. In the last 15 years, many scientific contributions have tackled these issues by investigating the possibility to develop a novel model of the eye-brain response to flicker and overcome the strict dependence of the standard on the kind of the light source. In this light of fact, this thesis is aimed at presenting an important contribution for a new Flickermeter. An improved visual system model using a physiological parameter that is the mean value of the pupil diameter, has been presented, thus allowing to get a more “objective” representation of the response to flicker. The system used to both generate flicker and measure the pupil diameter has been illustrated along with all the results of several experiments performed on the volunteers. The intent has been to demonstrate that the measurement of that geometrical parameter can give reliable information about the feeling of the human visual system to light flicker.

Congenital Nystagmus eye movements analysis and oculomotor system models evaluation

The term Congenital Nystagmus (Early Onset Nystagmus or Infantile Nystagmus Syndrome) refers to a pathology characterised by an involuntary movement of the eyes, which often seriously reduces a subject’s vision. Congenital Nystagmus (CN) is a specific kind of nystagmus within the wider classification of infantile nystagmus, which can be best recognized and classified by means of a combination of clinical investigations and motility analysis; in some cases, eye movement recording and analysis are indispensable for diagnosis. However, interpretation of eye movement recordings still lacks of complete reliability; hence new analysis techniques and precise identification of concise parameters directly related to visual acuity are necessary to further support physicians’ decisions. To this aim, an index computed from eye movement recordings and related to the visual acuity of a subject is proposed in this thesis. This estimator is based on two parameters: the time spent by a subject effectively viewing a target (foveation time - Tf) and the standard deviation of eye position (SDp). Moreover, since previous studies have shown that visual acuity largely depends on SDp, a data collection pilot study was also conducted with the purpose of specifically identifying eventual slow rhythmic component in the eye position and to characterise in more detail the SDp. The results are presented in this thesis. In addition, some oculomotor system models are reviewed and a new approach to those models, i.e. the recovery of periodic orbits of the oculomotor system in patients with CN, is tested on real patients data. In conclusion, the results obtained within this research consent to completely and reliably characterise the slow rhythmic component sometimes present in eye position recordings of CN subjects and to better classify the different kinds of CN waveforms. Those findings can successfully support the clinicians in therapy planning and treatment outcome evaluation.