50 research outputs found
A nonlinear complementary filter for underwater navigation using inertial measurements
This paper describes a nonlinear complementary filter capable of estimating the course motion variables namely the position, velocity, heading and accelerometers bias of an agile, over-actuated AUV during underwater operations, using the inertial sensors (IMU), the DVL, the depth sensor and the compass. The proposed work is within the framework of the V-Fides project, co-funded by Tuscany Region (Italy) and developed by a team lead by WASS S.p.A. (Whitehead Sistemi Subacquei, Livorno). The aim of the project was to develop and evaluate an high-depth, over-actuated, long endurance Autonomous Underwater Vehicle (AUV). The paper proposes the mathematical development of the observer, together with some experimental results, able to demonstrate the capabilities of the estimation scheme, compared with the estimations obtained via a standard Kalman Filter
Scaling Up Magnetic Nanobead Synthesis with Improved Stability for Biomedical Applications
The growing interest in multifunctional nano-objects based on polymers and magnetic nanoparticles for biomedical applications motivated us to develop a scale-up protocol to increase the yield of polymeric magnetic nanobeads while aiming at keeping the structural features at optimal conditions. The protocol was applied to two different types of magnetic ferrite nanoparticles: the Mn-ferrite selected for their properties as contrast agents in magnetic resonance imaging and iron oxide nanostar shaped nanoparticles chosen for their heat performance in magnetic hyperthermia. At the same time, some experiments on surface functionalization of nanobeads with amino modified polyethyelene glycol (PEG) molecules have provided further insight into the formation mechanism of magnetic nanobeads and the need to cross-link the polymer shell to improve the stability of the beads, making them more suitable for further manipulation and use. The present work summarizes the most important parameters required to be controlled for the upscaling of nanobead synthesis in a bench protocol and proposes an alternative cross-linking strategy based on prefunctionalization of the polymer prior to the nanobead formation as a key parameter to improve the nanobead structural stability in solutions at different pHs and during surface functionalization
Magnetic nanocarriers with tunable pH dependence for controlled loading and release of cationic and anionic payloads.
Superparamagnetic nanocarriers with tunable pH dependence of the surface charge are designed by a simple co-precipitation method. By exploiting electrostatic interactions, cationic or anionic payloads can be adsorbed and desorbed depending on the pH. On three different resulting nanocarrier systems, experiments of loading and release of gold nanoparticles as well as effective siRNA loading and in vitro delivery on human cells are performed
Controlled Release of Doxorubicin Loaded within Magnetic Thermo-responsive Nanocarriers under Magnetic and Thermal Actuation in a Microfluidic Channel
We report a procedure to grow thermo-responsive polymer shells at the surface of magnetic nanocarriers made of multiple iron oxide superparamagnetic nanoparticles embedded in poly(maleic anhydride-alt-1-ocatadecene) polymer nanobeads. Depending on the comonomers and on their relative composition, tunable phase transition temperatures in the range between 26 and 47 °C under physiological conditions could be achieved. Using a suitable microfluidic platform combining magnetic nanostructures and channels mimicking capillaries of the circulatory system, we demonstrate that thermo-responsive nanobeads are suitable for localized drug delivery with combined thermal and magnetic activation. Below the critical temperature nanobeads are stable in suspension, retain their cargo, and cannot be easily trapped by magnetic fields. Increasing the temperature above the critical temperature causes the aggregation of nanobeads, forming clusters with a magnetic moment high enough to permit their capture by suitable magnetic g..
The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study
The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy
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The role of clinical and neuroimaging features in the diagnosis of CADASIL.
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. METHODS: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. RESULTS: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. CONCLUSIONS: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.The Lombardia GENS project has received funding from the Regione Lombardia Government as a Research Independent Project (DGR n°VIII/006128-12/12/2007). Lombardia GENS is an investigator-driven, academic, non-profit consortium and is publicly funded. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by the Cambridge University Hospitals NIHR Biomedical Research Centr
The Lesson We Can Learn from Familial ALS Patients Carrying a SOD1 Mutation
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease causing progressive death of the motor neurons in both brain cortex and spinal cord. Twenty per cent of ALS familial cases (fALS) are caused by a mutation in the SOD1 gene.
The SOD1 gene is located in the short arm of human chromosome 21 and consists of 5 exons encoding for 153 amino acids. More than 100 mutations have been identified that are spred in all parts of the SOD1 gene; the majority of them are missense mutations but there are both insertions and deletions. Two mutations, in 126 and 141 codons, define a signal stop that produces a shorter protein. Mutations have been found also in intronic parts of the gene in two ALS cases. All mutations behave as autosomal dominant traits except for the D90A and the L84F, that exist in both dominant and recessive forms.
Attempts to correlate genotype with phenotype demonstrated that prediction of disease severity based on age of onset and disease duration on the basis of the single SOD1 mutation remains uncertain. Some mutations are associated with early onset (L38V, G37S), while others are associated with particularly short (A4V) or relatively long (D100G) disease duration. Mutations in SOD1 gene were also found in ALS patients with no family history. Subjects with SOD1 mutations (L84F, L144F and D76V) that did not develop the disease were reported. Epidemiological data underline that, in some cases, a mutation is present only in a single population: A4T mutation in the Japanese population, D76V in the hispanic one, the L144F mutation in several patients coming from Slavic regions (Yugoslavia, Croatia). Correlation between sex, regional disease onset, age of onset and SOD1 gene mutations have not been found. SOD1 mutations have been divided in three groups considering the three-dimensional structure of the wt protein. One group of mutations occurs within the dimer interface (A4V), while another group is positioned in loop regions at the end of beta Ć’{strands (G93A). Mutant proteins falling into these two groups appear to have full SOD1 activity and biophysical properties similar to the wt SOD1 protein. The third group of mutations is located near the metal binding site, in particular the protein region that binds copper ion. These mutant proteins (H46R, H48Q) carry little amount of copper or zinc and have biophysical properties quite different from the wt SOD1 protein.
In fALS carrying a SOD1 mutation the mutated protein is the cause for the development of ALS. In fALS various mutated SOD1 proteins show unaltered enzymatic activity, thus suggesting that the mutations in SOD1 gene may act causing a toxic ¡§gain of function¡¨ in SOD1 rather than a loss of function. In fALS SOD1 accumulates within the cytoplasm of the motor neurons. Similarly in sporadic ALS, intracellular aggregates in motor neurons have been found, possibly containing SOD1. As ALS, several other neurodegenerative disorders, like Alzheimer¡¦s disease, Parkinson¡¦s disease and prion diseases, are characterized by the accumulation of specific proteins in the brain areas in which neuronal loss occurs. The majority of neurodegenerative disorders have both familial and sporadic presentation and the gene involved in the familial form encodes for the protein that accumulates in both familial and sporadic form. Moreover, the mutated proteins may function normally, but tend to accumulate in a conformation that hampers degradation (amyloid). While the specific features of each disorder is related to the affected neuronal population and to the protein involved, the common aspect relies in the mechanisms of cell death. In fact, many experimental data demonstrate that in neurodegenerative disorders a common apoptotic mechanism causes the neuronal death through the activation of different factors (such as cdk5, Apaf-1 and JNK) belonging to the same pathway.
We think that the neuronal cell peculiar condition of being unable to replicate is of fundamental importance in understanding neurodegeneration. In the CNS the condition of permanent neuronal cells throughout the individual life span exists only by the strict interaction between neurons and glial cells. In ALS peripheral blood cells express mutated SOD1 and display alterations in mitochondrial metabolism and calcium homeostasis, but they show no degeneration. In our hypothesis neurodegenerative diseases are the expression of a general difficulty in degradation of misfolded proteins that are toxic to the cell. Whereas replicating tissues can resolve such problem by replacing itscellular components, nervous tissue can not. This is the reason why only neurons contain the aggregated protein. This could also explain why neurodegeneration and aging are so closely related
A Randomized Phase III study: Comparison between Intra-venous and Intra-arterial ACNU Administration in Newly Diagnosed Primary Glioblastomas.
Optimal aided inertial navigation, augmented with inter-sensors self-calibration
The proposed work is in the framework of the V-Fides project, in which is a general purpose, 3000m depth rated underwater vehicle with highly maneuverability capabilities was developed. The project was co-funded by Tuscany Region (Italy) and developed by a team lead by WASS S.p.A. (Whitehead Sistemi Subacquei, Livorno) with the participation of several partners including two research institutions of the University of Pisa and Small-Medium Enterprises in the Pisa-Livorno area. The vehicle is equipped with a sensors payload for autonomous navigation. This contribution describes an integrated calibration/navigation filter capable of estimating the relative (rotational) calibration parameters between the IMU and the DVL, and producing the standard velocity and attitude navigation output together with accelerometers biases. The results were demonstrated with real data sets collected during extensive experimental campaigns. Finally the observability analysis is proposed in order to define the motion requirements for the asymptotic convergence of the parameter estimates
The project V-fides: A new generation AUV for deep underwater exploration, operation and monitoring
The proposed work is in the framework of the V-Fides project, aiming at developing a new generation of agile, over-actuated, long endurance Autonomous Underwater Vehicles, for deep underwater exploration, operation and monitoring. The project is co-funded by Tuscany Region (Italy) and is developed by a team lead by WASS S.p.A. (Whitehead Sistemi Subacquei, Livorno) with the participation of several partners including two research institutions of the University of Pisa and Small-Medium Enterprises in the Pisa-Livorno area. The vehicle is a general purpose, 3000m depth rated underwater vehicle with highly maneuverability capabilities, which can operate both as AUV and ROV. The vehicle is equipped with seven thrusters, with asymmetric input-output characteristic, and with a sensors payload for autonomous navigation, composed by: a tactical grade Inertial Measurement Unit (IMU), a Doppler Velocity Logger (DVL), a depth sensor, a magnetic compass and an acoustic modem for underwater communication and localization. This contribution gives an overview of the developed general architecture of the Navigation and Control module of the vehicle, from the algorithmic and system implementation stand-points