Compact, High Energy 2-micron Coherent Doppler Wind Lidar Development for NASA's Future 3-D Winds Measurement from Space

This paper presents an overview of 2-micron laser transmitter development at NASA Langley Research Center for coherent-detection lidar profiling of winds. The novel high-energy, 2-micron, Ho:Tm:LuLiF laser technology developed at NASA Langley was employed to study laser technology currently envisioned by NASA for future global coherent Doppler lidar winds measurement. The 250 mJ, 10 Hz laser was designed as an integral part of a compact lidar transceiver developed for future aircraft flight. Ground-based wind profiles made with this transceiver will be presented. NASA Langley is currently funded to build complete Doppler lidar systems using this transceiver for the DC-8 aircraft in autonomous operation. Recently, LaRC 2-micron coherent Doppler wind lidar system was selected to contribute to the NASA Science Mission Directorate (SMD) Earth Science Division (ESD) hurricane field experiment in 2010 titled Genesis and Rapid Intensification Processes (GRIP). The Doppler lidar system will measure vertical profiles of horizontal vector winds from the DC-8 aircraft using NASA Langley s existing 2-micron, pulsed, coherent detection, Doppler wind lidar system that is ready for DC-8 integration. The measurements will typically extend from the DC-8 to the earth s surface. They will be highly accurate in both wind magnitude and direction. Displays of the data will be provided in real time on the DC-8. The pulsed Doppler wind lidar of NASA Langley Research Center is much more powerful than past Doppler lidars. The operating range, accuracy, range resolution, and time resolution will be unprecedented. We expect the data to play a key role, combined with the other sensors, in improving understanding and predictive algorithms for hurricane strength and track.

An expression signature of the angiogenic response in gastrointestinal neuroendocrine tumours: correlation with tumour phenotype and survival outcomes.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are heterogeneous with respect to biological behaviour and prognosis. As angiogenesis is a renowned pathogenic hallmark as well as a therapeutic target, we aimed to investigate the prognostic and clinico-pathological role of tissue markers of hypoxia and angiogenesis in GEP-NETs. METHODS: Tissue microarray (TMA) blocks were constructed with 86 tumours diagnosed from 1988 to 2010. Tissue microarray sections were immunostained for hypoxia inducible factor 1α (Hif-1α), vascular endothelial growth factor-A (VEGF-A), carbonic anhydrase IX (Ca-IX) and somatostatin receptors (SSTR) 1–5, Ki-67 and CD31. Biomarker expression was correlated with clinico-pathological variables and tested for survival prediction using Kaplan–Meier and Cox regression methods. RESULTS: Eighty-six consecutive cases were included: 51% male, median age 51 (range 16–82), 68% presenting with a pancreatic primary, 95% well differentiated, 51% metastatic. Higher grading (P=0.03), advanced stage (P<0.001), high Hif-1α and low SSTR-2 expression (P=0.03) predicted for shorter overall survival (OS) on univariate analyses. Stage, SSTR-2 and Hif-1α expression were confirmed as multivariate predictors of OS. Median OS for patients with SSTR-2+/Hif-1α-tumours was not reached after median follow up of 8.8 years, whereas SSTR-2-/Hif-1α+ GEP-NETs had a median survival of only 4.2 years (P=0.006). CONCLUSION: We have identified a coherent expression signature by immunohistochemistry that can be used for patient stratification and to optimise treatment decisions in GEP-NETs independently from stage and grading. Tumours with preserved SSTR-2 and low Hif-1α expression have an indolent phenotype and may be offered less aggressive management and less stringent follow up

TH17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26.

Interleukin 17-producing helper T cells (TH17 cells) have a major role in protection against infections and in mediating autoimmune diseases, yet the mechanisms involved are incompletely understood. We found that interleukin 26 (IL-26), a human TH17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, TH17 cell-derived IL-26 formed complexes with bacterial DNA and self-DNA released by dying bacteria and host cells. The resulting IL-26-DNA complexes triggered the production of type I interferon by plasmacytoid dendritic cells via activation of Toll-like receptor 9, but independently of the IL-26 receptor. These findings provide insights into the potent antimicrobial and proinflammatory function of TH17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death

Development and validation of a severity scale for leprosy Type 1 Reactions

Objectives: To develop a valid and reliable quantitative measure of leprosy Type 1 reactions.Methods: A scale was developed from previous scales which had not been validated. The face and content validity were assessed following consultation with recognised experts in the field. The construct validity was determined by applying the scale to patients in Bangladesh and Brazil who had been diagnosed with leprosy Type 1 reaction. An expert categorized each patient's reaction as mild or moderate or severe. Another worker applied the scale. This was done independently. In a subsequent stage of the study the agreement between two observers was assessed.Results: The scale had good internal consistency demonstrated by a Cronbach's alpha &gt;0.8. Removal of three items from the original scale resulted in better discrimination between disease severity categories. Cut off points for Type 1 reaction severities were determined using Receiver Operating Characteristic curves. A mild Type 1 reaction is characterized using the final scale by a score of 4 or less. A moderate reaction is a score of between 4.5 and 8.5. A severe reaction is a score of 9 or more.Conclusions: We have developed a valid and reliable tool for quantifying leprosy Type 1 reaction severity and believe this will be a useful tool in research of this condition, in observational and intervention studies, and in the comparison of clinical and laboratory parameters.<br/

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Circulating Transcript Analysis (NETest) in GEP-NETs Treated With Somatostatin Analogs Defines Therapy

Context: Early and precise delineation of therapeutic responses are key issues in neuroendocrine neoplasm/tumor management. Imaging is currently used but exhibits limitations in sensitivity and specificity. The utility of biomarkers is unclear. Objective, Setting, and Design: This prospective cohort study (11 mo) sought to determine whether measurements of circulating neuroendocrine tumor transcripts (NETest) predict responses to somatostatin analogs (SSAs). Patients: The test set consisted of 35 SSA-treated gastroenteropancreatic-NETs (RECISTevaluated). The prospective set consisted of 28 SSA-treated Grade 1–Grade 2 GEP-NETs. Intervention(s): Whole blood for transcript analysis (NETest) and plasma for Chromogranin A (CgA) (baseline), were collected every 4 weeks (prior to SSA injection). Morphologic (multidetector computed tomography/MRI) and functional imaging (99mTc-[HYNIC, Tyr3]-Octreotide) was undertaken at entry and 6-month intervals until progression (RECIST 1.0). Main Outcome Measure(s): Treatment response. Results: Test set: NETest (≥80%; scale, 0–100%) differentiated stable (SD) and progressive (PD) disease (P &lt; .0001). Prospective set: 28 patients (26/28 SD) undergoing standard SSA. Grading: 12 G1, 16 G2. SSA Response: progression-free survival: 315 days: 14 (50%) SD, 14 (50%) PD. NETest: Twenty had elevated (≥80%) values; 14 developed PD; six, SD. CgA: Twelve of 28 exhibited elevated baseline values and/or subsequent &gt;25% increase; eight developed PD; four, SD. NETest (P = .002) and grade (P = .054) were the only factors associated with treatment response. Multiple regression analysis established that the NETest could predict disease progression (P = .0002). NETest changes occurred significantly earlier (146 d prior to progression vs 56 d CgA; P &lt; .0001; χ2 = 19) and in more patients (100 vs 57%; P &lt; .02). Conclusions: NETest values (80–100%) were more accurate and occurred at a significantly earlier time point than CgA and predicted SSA treatment response

A rare combination of an endocrine tumour of the common bile duct and a follicular lymphoma of the ampulla of Vater: a case report and review of the literature

Carcinoid tumours of the common bile duct represent an extremely rare entity. Similarly, primary follicular lymphomas of the ampulla of Vater constitute an infrequent neoplasia. Herein, we report the first case of a synchronous development of a carcinoid tumour of the common bile duct and an ampullary follicular lymphoma that was treated surgically with a Whipple's procedure, due to inability to establish definitive preoperative diagnosis despite the extensive diagnostic investigation