Experimental demonstration of a classical analog to quantum noise cancellation for use in gravitational wave detection

We present results that are a classical analog to quantum noise cancellation. It is possible to breach the standard quantum limit in an interferometer by the use of squeezing to correlate orthogonal quadratures of quantum noise, causing their effects on the resulting sensitivity to cancel. A laser beam incident on a Fabry-Perot cavity was imprinted with classical, correlated noise in the same quadratures that cause shot noise and radiation pressure noise. Couplings between these quadratures due to a movable mirror, sensitive to radiation pressure, cause the excess classical noise to cancel. This cancellation was shown to improve the signal to noise ratio of an injected signal by approximately a factor of 10

Squeezing in the audio gravitational wave detection band

We demonstrate the generation of broad-band continuous-wave optical squeezing down to 200Hz using a below threshold optical parametric oscillator (OPO). The squeezed state phase was controlled using a noise locking technique. We show that low frequency noise sources, such as seed noise, pump noise and detuning fluctuations, present in optical parametric amplifiers have negligible effect on squeezing produced by a below threshold OPO. This low frequency squeezing is ideal for improving the sensitivity of audio frequency measuring devices such as gravitational wave detectors.Comment: 5 pages, 6 figure

Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?

<p>Abstract</p> <p>Background</p> <p>Pain is often a dominant clinical feature of chronic pancreatitis but the frequency and severity is highly variable between subjects. We hypothesized that genetic polymorphisms contribute to variations in clinical pain patterns. Since genetic variations in the GTP cyclohydrolase (GCH1) gene have been reported to protect some patients from pain, we investigated the effect of the "pain protective haplotype" in well characterized patients with chronic pancreatitis (CP) or recurrent acute pancreatitis (RAP) from the North American Pancreatitis Study 2 (NAPS2).</p> <p>Results</p> <p>Subjects in the NAPS2 study were asked to rank their pain in one of 5 categories reflecting different levels of pain frequency and severity. All subjects were genotyped at rs8007267 and rs3783641 to determine the frequency of the GCH1 pain-protective haplotype. In Caucasian subjects the frequency of the pain-protective GCH1 haplotype was no different in the control group (n = 236), CP patients (n = 265), RAP patients (N = 131), or in CP patients subclassified by pain category compared to previously reported haplotype frequencies in the general Caucasian population.</p> <p>Conclusion</p> <p>The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in RAP or CP. These results are important for helping to define the regulators of visceral pain, and to distinguish different mechanisms of pain.</p

Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop

A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities

OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients. METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL. RESULTS: Mean PCS and MCS scores were 36.7+/-11.7 and 42.4+/-12.2, respectively. Significant (P \u3c 0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild-moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild-moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P \u3c 0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8-6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL. CONCLUSIONS: Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses

Enhanced Neutrophil Extracellular Trap Formation in Acute Pancreatitis Contributes to Disease Severity and Is Reduced by Chloroquine

Background: Neutrophil extracellular traps (NETs) are generated when activated neutrophils, driven by PAD4, release their DNA, histones, HMGB1, and other intracellular granule components. NETs play a role in acute pancreatitis, worsening pancreatic inflammation, and promoting pancreatic duct obstruction. The autophagy inhibitor chloroquine (CQ) inhibits NET formation; therefore, we investigated the impact of CQ mediated NET inhibition in murine models of pancreatitis and human correlative studies. Methods: L-arginine and choline deficient ethionine supplemented (CDE) diet models of acute pancreatitis were studied in wild type and PAD4−/− mice, incapable of forming NETs. Isolated neutrophils were stimulated to induce NET formation and visualized with fluorescence microscopy. CQ treatment (0.5 mg/ml PO) was initiated after induction of pancreatitis. Biomarkers of NET formation, including cell-free DNA, citrullinated histone H3 (CitH3), and MPO-DNA conjugates were measured in murine serum and correlative human patient serum samples. Results: We first confirmed the role of NETs in the pathophysiology of acute pancreatitis by demonstrating that PAD4−/− mice had decreased pancreatitis severity and improved survival compared to wild-type controls. Furthermore, patients with severe acute pancreatitis had elevated levels of cell-free DNA and MPO-DNA conjugates, consistent with NET formation. Neutrophils from mice with pancreatitis were more prone to NET formation and CQ decreased this propensity to form NETs. CQ significantly reduced serum cell-free DNA and citrullinated histone H3 in murine models of pancreatitis, increasing survival in both models. Conclusions: Inhibition of NETs with CQ decreases the severity of acute pancreatitis and improves survival. Translating these findings into clinical trials of acute pancreatitis is warranted

Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer

Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes are clinically significant; however, currently, there is no validated method to differentiate these diabetes subtypes. We describe a study, "Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study," that seeks to address this knowledge gap. The DETECT study is a multicenter study that will examine differences in hormone and glucose excursions after a mixed meal test. The study will also create a biorepository that will be used to evaluate novel diagnostic biomarkers for differentiating these diabetes subtypes

Pathways to Injury in Chronic Pancreatitis: Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis

Background: The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP) are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways) that are initiated by different metabolic or environmental factors (etiologies) and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis. Methods and Findings: The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls) using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93), but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85) was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67) or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56). Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I2 = 80.95%. Conclusion: The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint. © 2008 Aoun MD et al