Lung cancer screening in 2008: A review and update

SummaryThis article discusses the strengths and weaknesses of using sputum cytology, plain chest radiograph and computerized tomography (CT) as screening modalities for lung cancer and provides recommendations for screening

Medical training simulation for central venous catheterization

Our Creative Inquiry, in collaboration with clinicians, local hospitals, and MBA students, has involved the development, testing, and commercialization of a central venous catheterization training simulator. Medical training simulators are important tools for educating physicians without needing to practice on patients. Central venous catheterization (CVC) is the insertion of a catheter into a sizable vein in order to deliver a large influx of drugs to the heart. The risky nature of the procedure comes from the proximity of the vein to the heart, lungs, and major arteries. Many complications can arise, often the cause of expensive and ineffective training methods. We have created an affordable simulator with features that address the limitations of current simulators, including a fully rotatable head, proper anatomical landmarks, and ultrasoundability. Our patent-pending design is currently being prepared for manufacturing and marketing in hopes of increasing the safety of CVC procedures

Space Shuttle Body Flap Actuator Bearing Testing for NASA Return to Flight

The Space Shuttle body flap is located beneath the main engine nozzles and is required for proper aerodynamic control during orbital descent. Routine inspection of one of four body flap actuators found one of the actuator bearings had degraded and blackened balls. A test program was initiated to demonstrate that it is acceptable to operate bearings which are degraded from operation over several flights. This test exposed the bearing to predicted flight axial loads, speeds and temperatures. Testing at 140 F has been completed, and results indicate the previously flown bearings are acceptable for up to 12 additional missions. Additional testing is underway to determine the lubricant life at various temperatures and stresses and to further understand the mechanism that caused the blacken balls. Initial results of this testing indicates that bearing life is shorten at room temperature possibly due fact that higher temperature (140 F) accelerates the flow of grease and oil into the wear surfac

Polygenic risk associated with post-traumatic stress disorder onset and severity.

Post-traumatic stress disorder (PTSD) is a psychiatric illness with a highly polygenic architecture without large effect-size common single-nucleotide polymorphisms (SNPs). Thus, to capture a substantial portion of the genetic contribution, effects from many variants need to be aggregated. We investigated various aspects of one such approach that has been successfully applied to many traits, polygenic risk score (PRS) for PTSD. Theoretical analyses indicate the potential prediction ability of PRS. We used the latest summary statistics from the largest published genome-wide association study (GWAS) conducted by Psychiatric Genomics Consortium for PTSD (PGC-PTSD). We found that the PRS constructed for a cohort comprising veterans of recent wars (n = 244) explains a considerable proportion of PTSD onset (Nagelkerke R2 = 4.68%, P = 0.003) and severity (R2 = 4.35%, P = 0.0008) variances. However, the performance on an African ancestry sub-cohort was minimal. A PRS constructed with schizophrenia GWAS also explained a significant fraction of PTSD diagnosis variance (Nagelkerke R2 = 2.96%, P = 0.0175), confirming previously reported genetic correlation between the two psychiatric ailments. Overall, these findings demonstrate the important role polygenic analyses of PTSD will play in risk prediction models as well as in elucidating the biology of the disorder

Audit of the autoantibody test, EarlyCDT®-Lung, in 1600 patients: An evaluation of its performance in routine clinical practice

ObjectivesEarlyCDT®-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient.MethodsClinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging.ResultsSix month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity = 41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II.ConclusionsEarlyCDT-Lung has been extensively tested and validated in case–control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer

Three-Dimensional Flow Field Measurements in a Transonic Turbine Cascade

Three-dimensional flow field measurements are presented for a large scale transonic turbine blade cascade. Flow field total pressures and pitch and yaw flow angles were measured at an inlet Reynolds number of 1.0 x 10(exp 6) and at an isentropic exit Mach number of 1.3 in a low turbulence environment. Flow field data was obtained on five pitchwise/spanwise measurement planes, two upstream and three downstream of the cascade, each covering three blade pitches. Three-hole boundary layer probes and five-hole pitch/yaw probes were used to obtain data at over 1200 locations in each of the measurement planes. Blade and endwall static pressures were also measured at an inlet Reynolds number of 0.5 x 10(exp 6) and at an isentropic exit Mach number of 1.0. Tests were conducted in a linear cascade at the NASA Lewis Transonic Turbine Blade Cascade Facility. The test article was a turbine rotor with 136 deg of turning and an axial chord of 12.7 cm. The flow field in the cascade is highly three-dimensional as a result of thick boundary layers at the test section inlet and because of the high degree of flow turning. The large scale allowed for very detailed measurements of both flow field and surface phenomena. The intent of the work is to provide benchmark quality data for CFD code and model verification

Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily

BACKGROUND: The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. OBJECTIVES: We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1-4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 mg/kg/day diazinon. METHODS: Using microarrays, we then examined the regional expression of mRNAs encoding the FGFs and their receptors (FGFRs) in the forebrain and brain stem. RESULTS: Chlorpyrifios and diazinon both markedly suppressed fgf20 expression in the forebrain and fgf2 in the brain stem, while elevating brain stem fgfr4 and evoking a small deficit in brain stem fgfr22. However, they differed in that the effects on fgf2 and f4 were significantly larger for diazinon, and the two agents also showed dissimilar, smaller effects on fgf11, fgf14, and fgfr1. CONCLUSIONS: The fact that there are similarities but also notable disparities in the responses to chlorpyrifos and diazinon, and that robust effects were seen even at doses that do not inhibit cholinesterase, supports the idea that organophosphates differ in their propensity to elicit developmental neurotoyicity, unrelated to their anticholinesterase activity. Effects on neurotrophic factors provide a mechanistic link between organophosphate injury to developing neurons and the eventual, adverse neurodevelopmental outcome

Diffusion of Zn into GaAs and AlGaAs from isothermal Liquid-phase epitaxy solutions

In this work we present results of zinc diffusion in GaAs using the liquid phase epitaxy technique from liquid solutions of Ga‐As‐Zn and Ga‐As‐Al‐Zn. Using silicon‐doped n‐GaAs substrates, working at a diffusion temperature of 850 °C, and introducing a dopant concentration ranging 1018–1019 cm−3, the most important findings regarding the diffusion properties are as follows: (a) zinc concentration in the solid depends on the square root of zinc atomic fraction in the liquid; (b) the diffusion is dominated by the interstitial‐substitutional process; (c) the diffusivity D varies as about C3 in the form D=2.9×10−67C3.05; (d) aluminum plays the role of the catalyst of the diffusion process, if it is introduced in the liquid solution, since it is found that D varies as (γAsXlAs)−1; (e) the zinc interstitial is mainly doubly ionized (Zn++i); (f) the zinc diffusion coefficient in Al0.85 Ga0.15 As is about four times greater than in GaAs; (g) by means of all these results, it is possible to control zinc diffusion processes in order to obtain optimized depth junctions and doping levels in semiconductor device fabrication

Ultrasensitive flow cytometric analyses

New techniques and approaches to cellular analysis being developed at the Los Alamos National Flow Cytometry Resource can be divided into those that improve sensitivity and those that move the technology into new areas by refining existing approaches. An example of the first category is a flow cytometric system capable of measuring the phase shift of fluorescence emitted by fluorophors bound to cells is being assembled. This phase sensitive cytometer is be capable of quantifying fluorescence life time on a cell-by-cell basis as well as using the phase sensitive detection to separate fluorescence emissions that overlap spectrally but have different lifetimes. A Fourier transform flow cytometer capable of measuring the fluorescence emission spectrum of individual labeled cells at rates approaching several hundred per second is also in the new technology category. The current implementation is capable of resolving the visible region of the spectrum into 8 bands. With this instrument, it is possible to resolve the contributions of fluorophors with overlapping emission spectra and to determine the emission spectra of dyes such as calcium concentration indicators that are sensitive to the physiological environment. Flow cytometric techniques have been refined to the point that it is possible to detect individual fluorescent molecules in solution as they flow past a laser beam. This capability has lead to a rapid DNA sequencing project. The goal of the project is to develop a technique that is capable of sequencing long strands of DNA (40,000 kb) at a rate of between 100 and 1,000 bases per second

Predictive biomarkers for response to EGFR-directed monoclonal antibodies for advanced squamous cell lung cancer

Writing assistance was funded by Eli Lilly and Company (no grant numbers apply).Peer reviewedPublisher PD