Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD

PURPOSE: To test the hypothesis that the extension of areas with increased fundus autofluorescence (FAF) outside atrophic patches correlates with the rate of spread of geographic atrophy (GA) over time in eyes with age-related macular degeneration (AMD). METHODS: The database of the multicenter longitudinal natural history Fundus Autofluorescence in AMD (FAM) Study was reviewed for patients with GA recruited through the end of August 2003, with follow-up examinations within at least 1 year. Only eyes with sufficient image quality and with diffuse patterns of increased FAF surrounding atrophy were chosen. In standardized digital FAF images (excitation, 488 nm; emission, >500 nm), total size and spread of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon encompassing the entire area of increased FAF surrounding the central atrophic patches was quantified at baseline. Statistical analysis was performed with the Spearman's rank correlation coefficient (rho). RESULTS: Thirty-nine eyes of 32 patients were included (median age, 75.0 years; interquartile range [IQR], 67.8-78.9); median follow-up, 1.87 years; IQR, 1.43-3.37). At baseline, the median total size of atrophy was 7.04 mm2 (IQR, 4.20-9.88). The median size of the CH was 21.47 mm2 (IQR, 15.19-28.26). The median rate of GA progression was 1.72 mm2 per year (IQR, 1.10-2.83). The area of increased FAF around the atrophy (difference between the CH and the total GA size at baseline) showed a positive correlation with GA enlargement over time (rho=0.60; P=0.0002). CONCLUSIONS: FAF characteristics that are not identified by fundus photography or fluorescein angiography may serve as a prognostic determinant in advanced atrophic AMD. As the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since increased FAF indicates excessive LF accumulation, these findings would underscore the pathophysiological role of RPE-LF in AMD pathogenesis.

Multimodal augmented reality system for surgical microscopy

Image-guided, computer-assisted neurosurgery has emerged to improve localization and targeting, to provide a better anatomic definition of the surgical field, and to decrease invasiveness. Usually, in image-guided surgery, a computer displays the surgical field in a CT/MR environment, using axial, coronal or sagittal views, or even a 3D representation of the patient. Such a system forces the surgeon to look away from the surgical scene to the computer screen. Moreover, this kind of information, being pre-operative imaging, can not be modified during the operation, so it remains valid for guidance in the first stage of the surgical procedure, and mainly for rigid structures like bones. In order to solve the two constraints mentioned before, we are developing an ultrasoundguided surgical microscope. Such a system takes the advantage that surgical microscopy and ultrasound systems are already used in neurosurgery, so it does not add more complexity to the surgical procedure. We have integrated an optical tracking device in the microscope and an augmented reality overlay system with which we avoid the need to look away from the scene, providing correctly aligned surgical images with sub-millimeter accuracy. In addition to the standard CT and 3D views, we are able to track an ultrasound probe, and using a previous calibration and registration of the imaging, the image obtained is correctly projected to the overlay system, so the surgeon can always localize the target and verify the effects of the intervention. Several tests of the system have been already performed to evaluate the accuracy, and clinical experiments are currently in progress in order to validate the clinical usefulness of the system.

Semaphorins guide PerPlexeD endothelial cells

Abrogation of the endothelial cell-specific semaphorin receptor PlexinD1 in zebrafish and mouse reveals semaphorin functions selectively affecting the cardiovascular system. Neuropilins team up with PlexinD1 to form a novel endothelial receptor complex for class 3 semaphorins.

Female patients with atherosclerotic lesions of the lower limbs. Not all are alike

BACKGROUND: Data on female patients with atherosclerotic peripheral arterial disease (PAD) are scarce, and limited primarily to the elderly population with multilevel disease. In this longitudinal observational study we compare female patients below 60 years of age with isolated lesions at the aortic bifurcation or focal superficial femoral artery disease. PATIENTS AND METHODS: Analysis is based on consecutive series of 43 female patients with PAD limited to the aortoiliac bifurcation (n = 28, group I) or an isolated femoral segment at the adductor channel (n = 15, group II) seen in a tertiary referral center between 1998 and 2000. The first assessment provided baseline data, with follow up data obtained at this study. Traditional risk factors, carotid artery disease and clinical outcome (mortality, cardiovascular events, vascular re-intervention rate, PAD progression) were evaluated over an interval of 5 (2 to 8) years. RESULTS: Female patients with aortic disease [group I] were younger (51.8 +/- 7.7 vs. 56.7 +/- 7.6 years in group II; p = 0.048), presented a more masculine phenotype, and smoked significantly more often (82% vs. 40%; p = 0.007). Arterial hypertension and diabetes mellitus were more common in group II, though it missed statistical significance (p = 0.068 and p = 0.085). Cardiovascular and limb outcome were comparable in both groups of female patients, while carotid artery disease was more severe in group I (i.e., carotid plaques in 71 vs. 53%). CONCLUSION: Our data support previous findings that cigarette smoking is a stronger risk factor for aortic disease as compared to femoral disease in younger female patients, with the strongest effect of smoking on a localized region of the aortic bifurcation.

Theoretical considerations to the verification of dynamic multileaf collimated fields with a SLIC-type portal image detector

The verification possibilities of dynamically collimated treatment beams with a scanning liquid ionization chamber electronic portal image device (SLIC-EPID) are investigated. The ion concentration in the liquid of a SLIC-EPID and therefore the read-out signal is determined by two parameters of a differential equation describing the creation and recombination of the ions. Due to the form of this equation, the portal image detector describes a nonlinear dynamic system with memory. In this work, the parameters of the differential equation were experimentally determined for the particular chamber in use and for an incident open 6 MV photon beam. The mathematical description of the ion concentration was then used to predict portal images of intensity-modulated photon beams produced by a dynamic delivery technique, the sliding window approach. Due to the nature of the differential equation, a mathematical condition for 'reliable leaf motion verification' in the sliding window technique can be formulated. It is shown that the time constants for both formation and decay of the equilibrium concentration in the chamber is in the order of seconds. In order to guarantee reliable leaf motion verification, these time constants impose a constraint on the rapidity of the image-read out for a given maximum leaf speed. For a leaf speed of 2 cm s(-1), a minimum image acquisition frequency of about 2 Hz is required. Current SLIC-EPID systems are usually too slow since they need about a second to acquire a portal image. However, if the condition is fulfilled, the memory property of the system can be used to reconstruct the leaf motion. It is shown that a simple edge detecting algorithm can be employed to determine the leaf positions. The method is also very robust against image noise.

Evaluation of 41calcium as a new approach to assess changes in bone metabolism: effect of a bisphosphonate intervention in postmenopausal women with low bone mass

A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. INTRODUCTION: Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. MATERIALS AND METHODS: Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. RESULTS: Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). CONCLUSIONS: Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.

Study of water use and supply in the district of Independencia, Peru

Peru is a developing country with abundant fresh water resources, yet the lack of infrastructure leaves much of the population without access to safe water for domestic uses. The author of this report was a Peace Corps Volunteer in the sector of water & sanitation in the district of Independencia, Ica, Peru. Independencia is located in the arid coastal region of the country, receiving on average 15 mm of rain annually. The water source for this district comes from the Pisco River, originating in the Andean highlands and outflowing into the Pacific Ocean near the town of Pisco, Peru. The objectives of this report are to assess the water supply and sanitation practices, model the existing water distribution system, and make recommendations for future expansion of the distribution system in the district of Independencia, Peru. The assessment of water supply will be based on the results from community surveys done in the district of Independencia, water quality testing done by a detachment of the U.S. Navy, as well as on the results of a hydraulic model built in EPANET 2.0 to represent the distribution system. Sanitation practice assessments will be based on the surveys as well as observations from the author while living in Peru. Recommendations for system expansions will be made based on results from the EPANET model and the municipality’s technical report for the existing distribution system. Household water use and sanitation surveys were conducted with 84 families in the district revealing that upwards of 85% store their domestic water in regularly washed containers with lids. Over 80% of those surveyed are drinking water that is treated, mostly boiled. Of those surveyed, over 95% reported washing their hands and over 60% mentioned at least one critical time for hand washing when asked for specific instances. From the surveys, it was also discovered that over 80% of houses are properly disposing of excrement, in either latrines or septic tanks. There were 43 families interviewed with children five years of age or under, and just over 18% reported the child had a case of diarrhea within the last month at the time of the interview. Finally, from the surveys it was calculated that the average water use per person per day is about 22 liters. Water quality testing carried out by a detachment of the U.S. Navy revealed that the water intended for consumption in the houses surveyed was not suitable for consumption, with a median E. coli most probable number of 47/100 ml for the 61 houses sampled. The median total coliforms was 3,000 colony forming units per 100 ml. EPANET was used to simulate the water delivery system and evaluate its performance. EPANET is designed for continuous water delivery systems, assuming all pipes are always flowing full. To account for the intermittent nature of the system, multiple EPANET network models were created to simulate how water is routed to the different parts of the system throughout the day. The models were created from interviews with the water technicians and a map of the system created using handheld GPS units. The purpose is to analyze the performance of the water system that services approximately 13,276 people in the district of Independencia, Peru, as well as provide recommendations for future growth and improvement of the service level. Performance evaluation of the existing system is based on meeting 25 liters per person per day while maintaining positive pressure at all nodes in the network. The future performance is based on meeting a minimum pressure of 20 psi in the main line, as proposed by Chase (2000). The EPANET model results yield an average nodal pressure for all communities of 71 psi, with a range from 1.3 – 160 psi. Thus, if the current water delivery schedule obtained from the local municipality is followed, all communities should have sufficient pressure to deliver 25 l/p/d, with the exception of Los Rosales, which can only supply 3.25 l/p/d. However, if the line to Los Rosales were increased from one to four inches, the system could supply this community with 25 l/p/d. The district of Independencia could greatly benefit from increasing the service level to 24-hour water delivery and a minimum of 50 l/p/d, so that communities without reliable access due to insufficient pressure would become equal beneficiaries of this invaluable resource. To evaluate the feasibility of this, EPANET was used to model the system with a range of population growth rates, system lifetimes, and demands. In order to meet a minimum pressure of 20 psi in the main line, the 6-inch diameter main line must be increased and approximately two miles of trench must be excavated up to 30 feet deep. The sections of the main line that must be excavated are mile 0-1 and 1.5-2.5, and the first 3.4 miles of the main line must be increased from 6 to 16 inches, contracting to 10 inches for the remaining 5.8 miles. Doing this would allow 24-hour water delivery and provide 50 l/p/d for a range of population growth rates and system lifetimes. It is expected that improving the water delivery service would reduce the morbidity and mortality from diarrheal diseases by decreasing the recontamination of the water due to transport and household storage, as well as by maintaining continuous pressure in the system to prevent infiltration of contaminated groundwater. However, this expansion must be carefully planned so as not to affect aquatic ecosystems or other districts utilizing water from the Pisco River. It is recommended that stream gaging of the Pisco River and precipitation monitoring of the surrounding watershed is initiated in order to begin a hydrological study that would be integrated into the district’s water resource planning. It is also recommended that the district begin routine water quality testing, with the results available to the public.

Quantum dot / optical protein bio-nano hybrid system biosensing

The integration of novel nanomaterials with highly-functional biological molecules has advanced multiple fields including electronics, sensing, imaging, and energy harvesting. This work focuses on the creation of a new type of bio-nano hybrid substrate for military biosensing applications. Specifically it is shown that the nano-scale interactions of the optical protein bacteriorhodopsin and colloidal semiconductor quantum dots can be utilized as a generic sensing substrate. This work spans from the basic creation of the protein to its application in a novel biosensing system. The functionality of this sensor design originates from the unique interactions between the quantum dot and bacteriorhodopsin molecule when in nanoscale proximity. A direct energy transfer relationship has been established between coreshell quantum dots and the optical protein bacteriorhodopsin that substantially enhances the protein’s native photovoltaic capabilities. This energy transfer phenomena is largely distance dependent, in the sub-10nm realm, and is characterized experimentally at multiple separation distances. Experimental results on the energy transfer efficiency in this hybrid system correlate closely to theoretical predictions. Deposition of the hybrid system with nano-scale control has allowed for the utilization of this energy transfer phenomena as a modulation point for a functional biosensor prototype. This work reveals that quantum dots have the ability to activate the bacteriorhodopsin photocycle through both photonic and non-photonic energy transfer mechanisms. By altering the energy transferred to the bacteriorhodopsin molecule from the quantum dot, the electrical output of the protein can be modulated. A biosensing prototype was created in which the energy transfer relationship is altered upon target binding, demonstrating the applicability of a quantum dot/bacteriorhodopsin hybrid system for sensor applications. The electrical nature of this sensing substrate will allow for its efficient integration into a nanoelectronics array form, potentially leading to a small-low power sensing platform for remote toxin detection applications.

Muffler characterization with implementation of the finite element method and experimental techniques

Determining how an exhaust system will perform acoustically before a prototype muffler is built can save the designer both a substantial amount of time and resources. In order to effectively use the simulation tools available it is important to understand what is the most effective tool for the intended purpose of analysis as well as how typical elements in an exhaust system affect muffler performance. An in-depth look at the available tools and their most beneficial uses are presented in this thesis. A full parametric study was conducted using the FEM method for typical muffler elements which was also correlated to experimental results. This thesis lays out the overall ground work on how to accurately predict sound pressure levels in the free field for an exhaust system with the engine properties included. The accuracy of the model is heavily dependent on the correct temperature profile of the model in addition to the accuracy of the source properties. These factors will be discussed in detail and methods for determining them will be presented. The secondary effects of mean flow, which affects both the acoustical wave propagation and the flow noise generation, will be discussed. Effective ways for predicting these secondary effects will be described. Experimental models will be tested on a flow rig that showcases these phenomena.

Control of recycle processes using neural networks combined with PID controller

This thesis is focused on the control of a system with recycle. A new control strategy using neural network combined with PID controller was proposed. The combined controller was studied and tested on the pressure control of a vaporizer inside a para-xylene production process. The major problems are the negative effects of recycle and the delays on instability and performance. The neural network was designed to move the process close to the set points while the PID accomplishes the finer level of disturbance rejection and offset reductions. Our simulation results show that during control, the neural network was able to determine the nonlinear relationship between steady state and manipulated variables. The results also show the disturbance rejection was handled by PID controller effectively.

Enhancing Optical Isolator Performance in Nonreciprocal Waveguide Arrays

We investigate the operation of optical isolators based on magneto-optics waveguide arrays beyond the coupled mode analysis. Semi-vectorial beam propagation simulations demonstrate that evanescent tail coupling and the effects of radiation are responsible for degrading the device’s performance. Our analysis suggests that these effects can be mitigated when the array size is scaled up. In addition, we propose the use of radiation blockers in order to offset some of these effects, and we show that they provide a dramatic improvement in performance. Finally, we also study the robustness of the system with respect to fabrication tolerances using the coupled mode theory. We show that small, random variations in the system’s parameters tend to average out as the number of optical guiding channels increases.

MODELING AND PROTOCOL DESIGN FOR EMERGING WIRELESS SYSTEMS

Mobile Mesh Network based In-Transit Visibility (MMN-ITV) system facilitates global real-time tracking capability for the logistics system. In-transit containers form a multi-hop mesh network to forward the tracking information to the nearby sinks, which further deliver the information to the remote control center via satellite. The fundamental challenge to the MMN-ITV system is the energy constraint of the battery-operated containers. Coupled with the unique mobility pattern, cross-MMN behavior, and the large-spanned area, it is necessary to investigate the energy-efficient communication of the MMN-ITV system thoroughly. First of all, this dissertation models the energy-efficient routing under the unique pattern of the cross-MMN behavior. A new modeling approach, pseudo-dynamic modeling approach, is proposed to measure the energy-efficiency of the routing methods in the presence of the cross-MMN behavior. With this approach, it could be identified that the shortest-path routing and the load-balanced routing is energy-efficient in mobile networks and static networks respectively. For the MMN-ITV system with both mobile and static MMNs, an energy-efficient routing method, energy-threshold routing, is proposed to achieve the best tradeoff between them. Secondly, due to the cross-MMN behavior, neighbor discovery is executed frequently to help the new containers join the MMN, hence, consumes similar amount of energy as that of the data communication. By exploiting the unique pattern of the cross-MMN behavior, this dissertation proposes energy-efficient neighbor discovery wakeup schedules to save up to 60% of the energy for neighbor discovery. Vehicular Ad Hoc Networks (VANETs)-based inter-vehicle communications is by now growingly believed to enhance traffic safety and transportation management with low cost. The end-to-end delay is critical for the time-sensitive safety applications in VANETs, and can be a decisive performance metric for VANETs. This dissertation presents a complete analytical model to evaluate the end-to-end delay against the transmission range and the packet arrival rate. This model illustrates a significant end-to-end delay increase from non-saturated networks to saturated networks. It hence suggests that the distributed power control and admission control protocols for VANETs should aim at improving the real-time capacity (the maximum packet generation rate without causing saturation), instead of the delay itself. Based on the above model, it could be determined that adopting uniform transmission range for every vehicle may hinder the delay performance improvement, since it does not allow the coexistence of the short path length and the low interference. Clusters are proposed to configure non-uniform transmission range for the vehicles. Analysis and simulation confirm that such configuration can enhance the real-time capacity. In addition, it provides an improved trade off between the end-to-end delay and the network capacity. A distributed clustering protocol with minimum message overhead is proposed, which achieves low convergence time.

Expression and hypoxic regulation of the endothelin system in endocrine cells of human and rat pancreatic islets

CONTEXT: The success of pancreatic islet transplantation depends largely on the capacity of the islet graft to survive the initial phase immediately after transplantation until revascularization is completed. Endothelin-1 (ET-1) is a strong vasoconstrictor which has been involved in solid organ graft failure but is also known to be a potent mitogenic/anti-apoptotic factor which could also potentially enhance the survival of the transplanted islets. OBJECTIVE: Characterization of the endothelin system with regard to a potential endothelin agonist/antagonist treatment. DESIGN: Regulated expression of the endothelin system in human and rat pancreatic islets and beta-cell lines was assessed by means of immunohistochemistry, competition binding studies, western blot, RT-PCR, real-time PCR and transplant studies. RESULTS: ET-1, ETA- and ETB-receptor immunoreactivity was identified in the endocrine cells of human and rat pancreatic islets. The corresponding mRNA was detectable in rat beta-cell lines and isolated rat and human pancreatic islets. Competition binding studies on rat islets revealed binding sites for both receptor types. ET-1 stimulated the phosphorylation of mitogen-activated protein kinase, which was prevented by ETA- and ETB-receptor antagonists. After exposure to hypoxia equal to post-transplant environment oxygen tension, mRNA levels of ET-1 and ETB-receptor of human islets were robustly induced whereas ETA-receptor mRNA did not show significant changes. Immunostaining signals for ET-1 and ETA-receptor of transplanted rat islets were markedly decreased when compared to native pancreatic sections. CONCLUSIONS: In pancreatic islets, ET-1 and its receptors are differentially expressed by hypoxia and after transplantation. Our results provide the biological basis for the study of the potential use of endothelin agonists/antagonists to improve islet transplantation outcome.

Colloidal Nano-apatite Particles with Active Luminescent and Magentic Properties for Biotechnology Applications

Colloidal Nano-apatite Particles with Active Luminescent and Magentic Properties for Biotechnology Applications. The synthesis of functional nano-materials is a burgeoning field that has produced remarkable and consistent breakthroughs over the last two decades. Individual particles have become smaller and shown potential for well defined functionality. However, there are still unresolved problems, a primary one being the loss of functionality and novelty due to uncontrolled aggregation driven by surface energy considerations. As such the first design criteria to harness the true potential of nanoparticles is to prevent unwanted agglomeration by: (1) improving, and, if possible, (2) controlling aggregation behavior. This requires specific knowledge of the chemistry of the immediate locale of the intended application; especially for biologically relevant applications. The latter criterion is also application driven but should be considered, generally, to diversify the range of functional properties that can be achieved. We have now reason to believe that such a novel system with multifunctional capabilities can be synthesized rather conveniently and have far reaching impact in biotechnology and other applications in the near future. We are presently experimenting with the syntheses of spheroidal, metal-doped, colloidal apatite nano-particles (~10 nm) for several potential biomedical applications.

HOUSEHOLD SOLAR POWER SYSTEM

Photovoltaic power has become one of the most popular research area in new energy field. In this report, the case of household solar power system is presented. Based on the Matlab environment, the simulation is built by using Simulink and SimPowerSystem. There are four parts in a household solar system, solar cell, MPPT system, battery and power consumer. Solar cell and MPPT system are been studied and analyzed individually. The system with MPPT generates 30% more energy than the system without MPPT. After simulating the household system, it is can be seen that the power which generated by the system is 40.392 kWh per sunny day. By combining the power generated by the system and the price of the electric power, 8.42 years are need for the system to achieve a balance of income and expenditure when weather condition is considered.