Hypogonadism in HIV-1-infected men is common and does not resolve during antiretroviral therapy

OBJECTIVES: To assess the prevalence of abnormal testosterone and gonadotropin values in HIV-infected men before and after 2 years of combination antiretroviral therapy (cART). DESIGN: Multicentre cohort of HIV-infected adults. METHODS: We identified 139 Caucasian antiretroviral-naive male patients who started zidovudine/ lamivudine-based cART that was virologically successful over a 2 year period. Ninety-seven were randomly chosen and plasma hormone determinations of free testosterone (fT) and luteinizing hormone (LH) at baseline and after 2 years of cART were evaluated. RESULTS: At baseline 68 patients (70%) had subnormal fT levels. In these, LH levels were low in 44%, normal in 47% and high in 9%. There was a trend for an association between lower CD4+ T-cell counts and hypogonadism. Most participants had normal FSH levels. No significant changes of fT, LH and FSH levels were observed after 2 years of cART. CONCLUSIONS: Low fT levels, mainly with normal or low LH levels and thus indicating secondary hypogonadism, are found in the majority of HIV-infected men and do not resolve during 2 years of successful cART.

Flow impairment during protected carotid artery stenting: impact of filter device design

PURPOSE: To investigate the impact of filter design on blood flow impairment in the internal carotid artery (ICA) among patients undergoing carotid artery stenting (CAS) using filter-type emboli protection devices (EPD). METHODS: Between July 2003 and March 2007, 115 filter-protected CAS procedures were performed at an academic institution in 107 consecutive patients (78 men; mean age 68 years, range 38-87). The Angioguard, FilterWire EZ, and Spider filters were used in 68 (59%), 32 (28%), and 15 (13%) of cases, respectively. Patient characteristics, procedural and angiographic data, and outcomes were prospectively entered into an electronic database and reviewed retrospectively along with all angiograms. RESULTS: Flow impairment while the filter was in place was observed in 25 (22%) cases. The presumptive reason of flow impairment was filter obstruction in 21 (18%) instances and flow-limiting spasm at the level of the filter in 4 (4%). In all cases, flow was restored after retrieval of the filter. Flow obstruction in the ICA occurred more frequently with Angioguard (22/68; 32.3%) than with FilterWire EZ (2/32; 6.2%) or Spider (1/15; 6.7%; p = 0.004). No flow occurred in 13 (19%) procedures, all of them protected with Angioguard; no patient treated with other devices experienced this event (p = 0.007). Two (8.0%) strokes occurred in procedures associated with flow impairment, while 1 (1.1%) event was observed in the presence of preserved flow throughout the intervention (p = 0.11). CONCLUSION: Flow impairment in the ICA during filter-based CAS is common and related to the type of filter used.

Study of and design procedure for dual circularly polarized waveguide slot arrays

For the past sixty years, waveguide slot radiator arrays have played a critical role in microwave radar and communication systems. They feature a well-characterized antenna element capable of direct integration into a low-loss feed structure with highly developed and inexpensive manufacturing processes. Waveguide slot radiators comprise some of the highest performance—in terms of side-lobe-level, efficiency, etc. — antenna arrays ever constructed. A wealth of information is available in the open literature regarding design procedures for linearly polarized waveguide slots. By contrast, despite their presence in some of the earliest published reports, little has been presented to date on array designs for circularly polarized (CP) waveguide slots. Moreover, that which has been presented features a classic traveling wave, efficiency-reducing beam tilt. This work proposes a unique CP waveguide slot architecture which mitigates these problems and a thorough design procedure employing widely available, modern computational tools. The proposed array topology features simultaneous dual-CP operation with grating-lobe-free, broadside radiation, high aperture efficiency, and good return loss. A traditional X-Slot CP element is employed with the inclusion of a slow wave structure passive phase shifter to ensure broadside radiation without the need for performance-limiting dielectric loading. It is anticipated this technology will be advantageous for upcoming polarimetric radar and Ka-band SatCom systems. The presented design methodology represents a philosophical shift away from traditional waveguide slot radiator design practices. Rather than providing design curves and/or analytical expressions for equivalent circuit models, simple first-order design rules – generated via parametric studies — are presented with the understanding that device optimization and design will be carried out computationally. A unit-cell, S-parameter based approach provides a sufficient reduction of complexity to permit efficient, accurate device design with attention to realistic, application-specific mechanical tolerances. A transparent, start-to-finish example of the design procedure for a linear sub-array at X-Band is presented. Both unit cell and array performance is calculated via finite element method simulations. Results are confirmed via good agreement with finite difference, time domain calculations. Array performance exhibiting grating-lobe-free, broadside-scanned, dual-CP radiation with better than 20 dB return loss and over 75% aperture efficiency is presented.

Sulfoxides as an intramolecular sulfenylating agent for indoles and diverse applications of the sulfide-sulfoxide redox cycle in organic chemistry

This dissertation involves study of various aspects of sulfoxide chemistry. Specifically designed t-butyl and propanenitrile sulfoxides tethered to indole-2-carboxamide were used as a source of intramolecular sulfenylating agents to synthesize novel indolo[3,2-b]-1-5-benzothiazepinones which are structurally analogous to the other biologically active benzothiazepinones. This study reveals that the intramolecular cyclization of sulfoxide follows an electrophilic sulfenylation (Sulfoxide Electrophilic Sulfenylation, SES) reaction pathway. Evidence of the absence of sulfenic acid as a transient reactive intermediate in such intramolecular cyclization is also provided. In another study, sulfoxide was used as a “protecting group” of thioether to synthesize 8-membered, indole substituted, thiazocine-2-acetic acid derivative via Ring Closing Metathesis (RCM). Protection (oxidation) of inert (to RCM) sulfide to sulfoxide followed by RCM produced cyclized product in good yields. Deprotection (reduction) of sulfoxide was achieved using Lawessons Reagent (L.R.). Application of the sulfide-sulfoxide redox cycle to solve the existing difficulties in using RCM methodology to thioethers is illustrated. A new design of a “molecular brake”, based on the sulfide-sulfoxide redox cycle is described. N-Ar rotation in simple isoindolines is controlled by the oxidation state of the proximate sulfur atom. Sulfide [S(II)] shows “free” [brake OFF] N-Ar rotation whereas sulfoxide displayed hindered [brake ON] N-Ar rotation. The semi-empirical molecular orbital (PM3) calculations revealed concerted pyramidalization of amidic nitrogen with N-Ar rotation.

International Common Otology Database: taste disturbance after stapes surgery

OBJECTIVE: To use a study on dysgeusia to assess the usefulness of an otology database. STUDY DESIGN: Data were extracted from the international Common Otology Database. INTERVENTION: Primary stapes operations. MAIN OUTCOME MEASURE AND RESULTS: From a cohort of 14 otologists, only 8 (57%) were able to satisfy external validation and maintain data input for a period of at least 6 months. The rates of dysgeusia varied from 0 to 39% at 3 months and 0 to 27% at 6 months. The percentages of patients with taste disturbance at 6 months in the "nerve-cut" and "nerve-preserved" groups were 22.7 and 10.9%, respectively, although this was not statistically significant (chi2; p = 0.325). CONCLUSION: Many surgeons found it difficult to maintain a prospective otology database. The rates of certain subjective symptoms such as dysgeusia are influenced by how vigorously the reviewers prompt the response from the patients. Dysgeusia after stapes surgery is common even if the chorda tympani nerve is preserved. Many patients whose chorda tympani nerve is divided may not complain of dysgeusia.

Control design and genetic algorithm optimization for electrostatic MEMS

This dissertation discusses structural-electrostatic modeling techniques, genetic algorithm based optimization and control design for electrostatic micro devices. First, an alternative modeling technique, the interpolated force model, for electrostatic micro devices is discussed. The method provides improved computational efficiency relative to a benchmark model, as well as improved accuracy for irregular electrode configurations relative to a common approximate model, the parallel plate approximation model. For the configuration most similar to two parallel plates, expected to be the best case scenario for the approximate model, both the parallel plate approximation model and the interpolated force model maintained less than 2.2% error in static deflection compared to the benchmark model. For the configuration expected to be the worst case scenario for the parallel plate approximation model, the interpolated force model maintained less than 2.9% error in static deflection while the parallel plate approximation model is incapable of handling the configuration. Second, genetic algorithm based optimization is shown to improve the design of an electrostatic micro sensor. The design space is enlarged from published design spaces to include the configuration of both sensing and actuation electrodes, material distribution, actuation voltage and other geometric dimensions. For a small population, the design was improved by approximately a factor of 6 over 15 generations to a fitness value of 3.2 fF. For a larger population seeded with the best configurations of the previous optimization, the design was improved by another 7% in 5 generations to a fitness value of 3.0 fF. Third, a learning control algorithm is presented that reduces the closing time of a radiofrequency microelectromechanical systems switch by minimizing bounce while maintaining robustness to fabrication variability. Electrostatic actuation of the plate causes pull-in with high impact velocities, which are difficult to control due to parameter variations from part to part. A single degree-of-freedom model was utilized to design a learning control algorithm that shapes the actuation voltage based on the open/closed state of the switch. Experiments on 3 test switches show that after 5-10 iterations, the learning algorithm lands the switch with an impact velocity not exceeding 0.2 m/s, eliminating bounce.

Orbits design for Leo space based solar power satellite system

Space Based Solar Power satellites use solar arrays to generate clean, green, and renewable electricity in space and transmit it to earth via microwave, radiowave or laser beams to corresponding receivers (ground stations). These traditionally are large structures orbiting around earth at the geo-synchronous altitude. This thesis introduces a new architecture for a Space Based Solar Power satellite constellation. The proposed concept reduces the high cost involved in the construction of the space satellite and in the multiple launches to the geo-synchronous altitude. The proposed concept is a constellation of Low Earth Orbit satellites that are smaller in size than the conventional system. For this application a Repeated Sun-Synchronous Track Circular Orbit is considered (RSSTO). In these orbits, the spacecraft re-visits the same locations on earth periodically every given desired number of days with the line of nodes of the spacecraft’s orbit fixed relative to the Sun. A wide range of solutions are studied, and, in this thesis, a two-orbit constellation design is chosen and simulated. The number of satellites is chosen based on the electric power demands in a given set of global cities. The orbits of the satellites are designed such that their ground tracks visit a maximum number of ground stations during the revisit period. In the simulation, the locations of the ground stations are chosen close to big cities, in USA and worldwide, so that the space power constellation beams down power directly to locations of high electric power demands. The j2 perturbations are included in the mathematical model used in orbit design. The Coverage time of each spacecraft over a ground site and the gap time between two consecutive spacecrafts visiting a ground site are simulated in order to evaluate the coverage continuity of the proposed solar power constellation. It has been observed from simulations that there always periods in which s spacecraft does not communicate with any ground station. For this reason, it is suggested that each satellite in the constellation be equipped with power storage components so that it can store power for later transmission. This thesis presents a method for designing the solar power constellation orbits such that the number of ground stations visited during the given revisit period is maximized. This leads to maximizing the power transmission to ground stations.

STATISTICAL METHODS FOR RARE AND COMMON VARIANT ASSOCIATION STUDIES

Complex human diseases are a major challenge for biological research. The goal of my research is to develop effective methods for biostatistics in order to create more opportunities for the prevention and cure of human diseases. This dissertation proposes statistical technologies that have the ability of being adapted to sequencing data in family-based designs, and that account for joint effects as well as gene-gene and gene-environment interactions in the GWA studies. The framework includes statistical methods for rare and common variant association studies. Although next-generation DNA sequencing technologies have made rare variant association studies feasible, the development of powerful statistical methods for rare variant association studies is still underway. Chapter 2 demonstrates two adaptive weighting methods for rare variant association studies based on family data for quantitative traits. The results show that both proposed methods are robust to population stratification, robust to the direction and magnitude of the effects of causal variants, and more powerful than the methods using weights suggested by Madsen and Browning [2009]. In Chapter 3, I extended the previously proposed test for Testing the effect of an Optimally Weighted combination of variants (TOW) [Sha et al., 2012] for unrelated individuals to TOW &ndash F, TOW for Family &ndash based design. Simulation results show that TOW &ndash F can control for population stratification in wide range of population structures including spatially structured populations, is robust to the directions of effect of causal variants, and is relatively robust to percentage of neutral variants. In GWA studies, this dissertation consists of a two &ndash locus joint effect analysis and a two-stage approach accounting for gene &ndash gene and gene &ndash environment interaction. Chapter 4 proposes a novel two &ndash stage approach, which is promising to identify joint effects, especially for monotonic models. The proposed approach outperforms a single &ndash marker method and a regular two &ndash stage analysis based on the two &ndash locus genotypic test. In Chapter 5, I proposed a gene &ndash based two &ndash stage approach to identify gene &ndash gene and gene &ndash environment interactions in GWA studies which can include rare variants. The two &ndash stage approach is applied to the GAW 17 dataset to identify the interaction between KDR gene and smoking status.