Social Security could improve its management and detection of postentitlement changes by using postadjudication appraisal data /

"January 20, 1984."

Presentation and detection of invasive melanoma in a high-risk population

Background: Early detection of melanoma has been encouraged in Queensland for many years, yet little is known about the patterns of detection and the way in which they relate to tumor thickness. Objective: Our purpose was to describe current patterns of melanoma detection in Queensland. Methods: This was a population-based study, comprising 3772 Queensland residents diagnosed with a histologically confirmed melanoma between 2000 and 2003. Results: Almost half (44.0%) of the melanomas were detected by the patients themselves, with physicians detecting one fourth (25.3%) and partners one fifth (18.6%). Melanomas detected by doctors were more likely to be thin (\0.75 mm) than those detected by the patient or other layperson. Melanomas detected during a deliberate skin examination were thinner than those detected incidentally. Limitations: Although a participation rate of 78% was achieved, as in any survey, nonresponse bias cannot be completely excluded, and the ability of the results to be generalized to other geographical areas is unknown. Conclusion: There are clear differences in the depth distribution of melanoma in terms of method of detection and who detects the lesions that are consistent with, but do not automatically lead to, the conclusion that promoting active methods of detection may be beneficial. ( J Am Acad Dermatol 2006;54:783-92.)

Protein oxidation:role in signalling and detection by mass spectrometry

Proteins can undergo a wide variety of oxidative post-translational modifications (oxPTM); while reversible modifications are thought to be relevant in physiological processes, non-reversible oxPTM may contribute to pathological situations and disease. The oxidant is also important in determining the type of oxPTM, such as oxidation, chlorination or nitration. The best characterized oxPTMs involved in signalling modulation are partial oxidations of cysteine to disulfide, glutathionylated or sulfenic acid forms that can be reversed by thiol reductants. Proline hydroxylation in HIF signalling is also quite well characterized, and there is increasing evidence that specific oxidations of methionine and tyrosine may have some biological roles. For some proteins regulated by cysteine oxidation, the residues and molecular mechanism involved have been extensively studied and are well understood, such as the protein tyrosine phosphatase PTP1B and MAP3 kinase ASK1, as well as transcription factor complex Keap1-Nrf2. The advances in understanding of the role oxPTMs in signalling have been facilitated by advances in analytical technology, in particular tandem mass spectrometry techniques. Combinations of peptide sequencing by collisionally induced dissociation and precursor ion scanning or neutral loss to select for specific oxPTMs have proved very useful for identifying oxidatively modified proteins and mapping the sites of oxidation. The development of specific labelling and enrichment procedures for S-nitrosylation or disulfide formation has proved invaluable, and there is ongoing work to establish analogous methods for detection of nitrotyrosine and other modifications.

Redox signalling and detection of protein oxidation by mass spectrometry

It is now recognised that redox control of proteins plays an important role in many signalling pathways both in health and disease. Proteins can undergo a wide variety of oxidative post-translational modifications (oxPTM); while the reversible modifications are thought to be most important in physiological processes, non-reversible oxPTM may contribute to pathological situations and disease. The oxidant is also important in determining the type of oxPTM (chlorination, nitration, etc.), and the susceptibilities of residues vary depending on their structural location. The best characterized oxPTMs involved in signalling modulation are partial oxidations of cysteine to the disulfide, glutathionylated or sulfenic acid forms, but there is increasing evidence that specific oxidations of methionine and tyrosine may have some biological roles. Well understood examples of oxidative regulation include protein tyrosine phosphatases, e.g. PTP1B/C, and members of the MAPK pathways such as MEKK1 and ASK1. Transcription factors such as NFkB and Nrf-2 are also regulated by redox-active cysteines. Improved methods for analysing specific oxPTMs in biological samples are critical for understanding the physiological and pathological roles of these changes, and tandem or MS3 mass spectrometry techniques interfaced with nano-LC separation are being now used. MS3 fragmentation markers for a variety of oxidized residues including tyrosine, tryptophan and proline have been identified, and a precursor ion scanning method that allows the selective identification of these oxPTMs in complex samples has been developed. Such advances in technology offer potential for biomarker development, disease diagnosis and understanding pathology.

Optimisation of chromatographic separation of oxidised phospholipids and detection with targeted approaches provides greater coverage of the oxidised lipidome

Phospholipid oxidation by adventitious damage generates a wide variety of products with potentially novel biological activities that can modulate inflammatory processes associated with various diseases. To understand the biological importance of oxidised phospholipids (OxPL) and their potential role as disease biomarkers requires precise information about the abundance of these compounds in cells and tissues. There are many chemiluminescence and spectrophotometric assays available for detecting oxidised phospholipids, but they all have some limitations. Mass spectrometry coupled with liquid chromatography is a powerful and sensitive approach that can provide detailed information about the oxidative lipidome, but challenges still remain. The aim of this work is to develop improved methods for detection of OxPLs by optimisation of chromatographic separation through testing several reverse phase columns and solvent systems, and using targeted mass spectrometry approaches. Initial experiments were carried out using oxidation products generated in vitro to optimise the chromatography separation parameters and mass spectrometry parameters. We have evaluated the chromatographic separation of oxidised phosphatidylcholines (OxPCs) and oxidised phosphatidylethanolamines (OXPEs) using C8, C18 and C30 reverse phase, polystyrene – divinylbenzene based monolithic and mixed – mode hydrophilic interaction (HILIC) columns, interfaced with mass spectrometry. Our results suggest that the monolithic column was best able to separate short chain OxPCs and OxPEs from long chain oxidised and native PCs and PEs. However, variation in charge of polar head groups and extreme diversity of oxidised species make analysis of several classes of OxPLs within one analytical run impractical. We evaluated and optimised the chromatographic separation of OxPLs by serially coupling two columns: HILIC and monolith column that provided us the larger coverage of OxPL species in a single analytical run.

Improved sampling and detection of ignitable liquid residues and explosives by mass spectrometry and ion mobility spectrometry

Fire debris evidence is submitted to crime laboratories to determine if an ignitable liquid (IL) accelerant was used to commit arson. An ignitable liquid residue (ILR) may be difficult to analyze due to interferences, complex matrices, degradation, and low concentrations of analytes. Debris from an explosion and pre-detonated explosive compounds are not trivial to detect and identify due to sampling difficulties, complex matrices, and extremely low amounts (nanogram) of material present. The focus of this research is improving the sampling and detection of ILR and explosives through enhanced sensitivity, selectivity, and field portable instrumentation. Solid Phase MicroExtraction (SPME) enhanced the extraction of ILR by two orders of magnitude over conventional activated charcoal strip (ACS) extraction. Gas chromatography tandem mass spectrometry (GC/MS/MS) improved sensitivity of ILR by one order of magnitude and explosives by two orders of magnitude compared to gas chromatography mass spectrometry (GC/MS). Improvements in sensitivity were attributed to enhanced selectivity. An interface joining SPME to ion mobility spectrometry (IMS) has been constructed and evaluated to improve field detection of hidden explosives. The SPME-IMS interface improved the detection of volatile and semi-volatile explosive compounds and successfully adapted the IMS from a particle sampler into a vapor sampler. ^

Improved dynamic headspace sampling and detection using capillary microextraction of volatiles coupled to gas chromatography mass spectrometry

Sampling and preconcentration techniques play a critical role in headspace analysis in analytical chemistry. My dissertation presents a novel sampling design, capillary microextraction of volatiles (CMV), that improves the preconcentration of volatiles and semivolatiles in a headspace with high throughput, near quantitative analysis, high recovery and unambiguous identification of compounds when coupled to mass spectrometry. The CMV devices use sol-gel polydimethylsiloxane (PDMS) coated microglass fibers as the sampling/preconcentration sorbent when these fibers are stacked into open-ended capillary tubes. The design allows for dynamic headspace sampling by connecting the device to a hand-held vacuum pump. The inexpensive device can be fitted into a thermal desorption probe for thermal desorption of the extracted volatile compounds into a gas chromatography-mass spectrometer (GC-MS). The performance of the CMV devices was compared with two other existing preconcentration techniques, solid phase microextraction (SPME) and planar solid phase microextraction (PSPME). Compared to SPME fibers, the CMV devices have an improved surface area and phase volume of 5000 times and 80 times, respectively. One (1) minute dynamic CMV air sampling resulted in similar performance as a 30 min static extraction using a SPME fiber. The PSPME devices have been fashioned to easily interface with ion mobility spectrometers (IMS) for explosives or drugs detection. The CMV devices are shown to offer dynamic sampling and can now be coupled to COTS GC-MS instruments. Several compound classes representing explosives have been analyzed with minimum breakthrough even after a 60 min. sampling time. The extracted volatile compounds were retained in the CMV devices when preserved in aluminum foils after sampling. Finally, the CMV sampling device were used for several different headspace profiling applications which involved sampling a shipping facility, six illicit drugs, seven military explosives and eighteen different bacteria strains. Successful detection of the target analytes at ng levels of the target signature volatile compounds in these applications suggests that the CMV devices can provide high throughput qualitative and quantitative analysis with high recovery and unambiguous identification of analytes.

Evaluation of non-contact sampling and detection of explosives using receiver operating characteristic curves

The growing need for fast sampling of explosives in high throughput areas has increased the demand for improved technology for the trace detection of illicit compounds. Detection of the volatiles associated with the presence of the illicit compounds offer a different approach for sensitive trace detection of these compounds without increasing the false positive alarm rate. This study evaluated the performance of non-contact sampling and detection systems using statistical analysis through the construction of Receiver Operating Characteristic (ROC) curves in real-world scenarios for the detection of volatiles in the headspace of smokeless powder, used as the model system for generalizing explosives detection. A novel sorbent coated disk coined planar solid phase microextraction (PSPME) was previously used for rapid, non-contact sampling of the headspace containers. The limits of detection for the PSPME coupled to IMS detection was determined to be 0.5-24 ng for vapor sampling of volatile chemical compounds associated with illicit compounds and demonstrated an extraction efficiency of three times greater than other commercially available substrates, retaining >50% of the analyte after 30 minutes sampling of an analyte spike in comparison to a non-detect for the unmodified filters. Both static and dynamic PSPME sampling was used coupled with two ion mobility spectrometer (IMS) detection systems in which 10-500 mg quantities of smokeless powders were detected within 5-10 minutes of static sampling and 1 minute of dynamic sampling time in 1-45 L closed systems, resulting in faster sampling and analysis times in comparison to conventional solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) analysis. Similar real-world scenarios were sampled in low and high clutter environments with zero false positive rates. Excellent PSPME-IMS detection of the volatile analytes were visualized from the ROC curves, resulting with areas under the curves (AUC) of 0.85-1.0 and 0.81-1.0 for portable and bench-top IMS systems, respectively. Construction of ROC curves were also developed for SPME-GC-MS resulting with AUC of 0.95-1.0, comparable with PSPME-IMS detection. The PSPME-IMS technique provides less false positive results for non-contact vapor sampling, cutting the cost and providing an effective sampling and detection needed in high-throughput scenarios, resulting in similar performance in comparison to well-established techniques with the added advantage of fast detection in the field.

Tsunami simulation and detection using global navigation satellite system reflectometry

In this thesis, research for tsunami remote sensing using the Global Navigation Satellite System-Reflectometry (GNSS-R) delay-Doppler maps (DDMs) is presented. Firstly, a process for simulating GNSS-R DDMs of a tsunami-dominated sea sur- face is described. In this method, the bistatic scattering Zavorotny-Voronovich (Z-V) model, the sea surface mean square slope model of Cox and Munk, and the tsunami- induced wind perturbation model are employed. The feasibility of the Cox and Munk model under a tsunami scenario is examined by comparing the Cox and Munk model- based scattering coefficient with the Jason-1 measurement. A good consistency be- tween these two results is obtained with a correlation coefficient of 0.93. After con- firming the applicability of the Cox and Munk model for a tsunami-dominated sea, this work provides the simulations of the scattering coefficient distribution and the corresponding DDMs of a fixed region of interest before and during the tsunami. Fur- thermore, by subtracting the simulation results that are free of tsunami from those with presence of tsunami, the tsunami-induced variations in scattering coefficients and DDMs can be clearly observed. Secondly, a scheme to detect tsunamis and estimate tsunami parameters from such tsunami-dominant sea surface DDMs is developed. As a first step, a procedure to de- termine tsunami-induced sea surface height anomalies (SSHAs) from DDMs is demon- strated and a tsunami detection precept is proposed. Subsequently, the tsunami parameters (wave amplitude, direction and speed of propagation, wavelength, and the tsunami source location) are estimated based upon the detected tsunami-induced SSHAs. In application, the sea surface scattering coefficients are unambiguously re- trieved by employing the spatial integration approach (SIA) and the dual-antenna technique. Next, the effective wind speed distribution can be restored from the scat- tering coefficients. Assuming all DDMs are of a tsunami-dominated sea surface, the tsunami-induced SSHAs can be derived with the knowledge of background wind speed distribution. In addition, the SSHA distribution resulting from the tsunami-free DDM (which is supposed to be zero) is considered as an error map introduced during the overall retrieving stage and is utilized to mitigate such errors from influencing sub- sequent SSHA results. In particular, a tsunami detection procedure is conducted to judge the SSHAs to be truly tsunami-induced or not through a fitting process, which makes it possible to decrease the false alarm. After this step, tsunami parameter estimation is proceeded based upon the fitted results in the former tsunami detec- tion procedure. Moreover, an additional method is proposed for estimating tsunami propagation velocity and is believed to be more desirable in real-world scenarios. The above-mentioned tsunami-dominated sea surface DDM simulation, tsunami detection precept and parameter estimation have been tested with simulated data based on the 2004 Sumatra-Andaman tsunami event.

I/Q imbalance in two-way AF relaying: Performance analysis and detection mode switch

This paper studies the impact of in-phase and quadrature-phase imbalance (IQI) in two-way amplify-and-forward (AF) relaying systems. In particular, the effective signal-to-interference-plus-noise ratio (SINR) is derived for each source node, considering four different linear detection schemes, namely, uncompensated (Uncomp) scheme, maximal-ratio-combining (MRC), zero-forcing (ZF) and minimum mean-square error (MMSE) based schemes. For each proposed scheme, the outage probability (OP) is investigated over independent, non-identically distributed Nakagami-m fading channels, and exact closed-form expressions are derived for the first three schemes. Based on the closed-form OP expressions, an adaptive detection mode switching scheme is designed for minimizing the OP of both sources. An important observation is that, regardless of the channel conditions and transmit powers, the ZF-based scheme should always be selected if the target SINR is larger than 3 (4.77dB), while the MRC-based scheme should be avoided if the target SINR is larger than 0.38 (-4.20dB).

The Burkholderia Cenocepacia OmpA-Like Protein BCAL2958: Identification, Characterization, and Detection of Anti-BCAL2958 Antibodies in Serum from B. Cepacia Complex-Infected Cystic Fibrosis Patients

Respiratory infections by bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among cystic fibrosis patients, highlighting the need for novel therapeutic strategies. In the present work we have studied the B. cenocepacia protein BCAL2958, a member of the OmpA-like family of proteins, demonstrated as highly immunogenic in other pathogens and capable of eliciting strong host immune responses. The encoding gene was cloned and the protein, produced as a 6× His-tagged derivative, was used to produce polyclonal antibodies. Bioinformatics analyses led to the identification of sequences encoding proteins with a similarity higher than 96 % to BCAL2958 in all the publicly available Bcc genomes. Furthermore, using the antibody it was experimentally demonstrated that this protein is produced by all the 12 analyzed strains from 7 Bcc species. In addition, results are also presented showing the presence of anti-BCAL2958 antibodies in sera from cystic fibrosis patients with a clinical record of respiratory infection by Bcc, and the ability of the purified protein to in vitro stimulate neutrophils. The widespread production of the protein by Bcc members, together with its ability to stimulate the immune system and the detection of circulating antibodies in patients with a documented record of Bcc infection strongly suggest that the protein is a potential candidate for usage in preventive therapies of infections by Bcc.

Respiratory electron transport activity in plankton: determinants and detection

Programa de doctorado en Oceanografía. La fecha de publicación es la fecha de lectura