Impact of Pain, Opioids, and the Mu-opioid Receptor on Progression and Survival in Patients With Newly Diagnosed Stage IV Pancreatic Cancer.

OBJECTIVES: Pancreatic adenocarcinoma is frequently associated with pain requiring opioid therapy. Opioids, however, have been implicated in causing tumor progression, ultimately shortening survival. We examined the impact of pain, opioid use, and the mu-opioid receptor (MOP-R) expression in tumor tissue on progression-free survival and overall survival of patients with metastatic pancreatic cancer. METHODS: We identified 103 patients with metastatic pancreatic adenocarcinoma receiving chemotherapy and abstracted data from Tumor Registry, in addition to pain, opioid exposure, carbohydrate antigen 19-9 values, survival, and imaging response. MOP-R expression was evaluated using an immunohistochemistry assay. The association of variables with progression-free survival and overall survival was analyzed in univariate and multivariate models. RESULTS: Patients with low opioid use (<5 mg oral morphine equivalent/d) survived longer than patients with high opioid (HO) use (≥5 mg oral morphine equivalent/d) (median overall survival of 315 vs. 150 d; hazard ratio [HR]=1.79; 95% confidence interval [CI]: 1.13, 2.84). This effect persisted on multivariate models (adjusted HR=2.76; 95% CI: 1.39, 5.48). Low opioid patients tended to respond better to treatment than HO patients, based on carbohydrate antigen 19-9. Patients with low MOP-R expression had longer median survival (230 vs. 193 d), though the HR was not significant (1.15; 95% CI: 0.71, 1.88). Baseline pain was not associated with outcomes. CONCLUSION: In patients with metastatic pancreatic adenocarcinoma, HO use is associated with decreased survival, but the severity of baseline pain and MOP-R expression score in tumor tissue does not correlate with clinical outcomes.

Miniature Fiber Optic Acoustic Pressure Sensors With Air-Backed Graphene Diaphragms.

Graphene has been known to possess exceptional mechanical properties, including its extremely high Young's modulus and atomic layer thickness. Although there are several reported fiber optic pressure sensors using graphene film, a key question that is not well understood is how the suspended graphene film interacts with the backing air cavity and affects the sensor performance. Based on our previous analytical model, we will show that the sensor performance suffers due to the significantly reduced mechanical sensitivity by the backing cavity. To remedy this limitation, we will, through experimental and numerical methods, investigate two approaches to enhance the sensitivity of fiber optic acoustic pressure sensors using graphene film. First, a graphene-silver composite diaphragm is used to enhance the optical sensitivity by increasing the reflectivity. Compared with a sensor with pure graphene diaphragm, graphene-silver composite can enhance the sensitivity by threefold, while the mechanical sensitivity is largely unchanged. Second, a fiber optic sensor is developed with enlarged backing air volume through the gap between an optical fiber and a silica capillary tube. Experimental results show that the mechanical sensitivity is increased by 10× from the case where the gap side space is filled. For both approaches, signal-to-noise ratio (SNR) is improved due to the enhanced sensitivity, and COMSOL Thermoviscous acoustics simulation compares well with the experimental results. This study is expected to not only enhance the understanding of fluid-structural interaction in sensor design but also benefit various applications requiring high-performance miniature acoustic sensors.

Automated Piston Gauge Calibration System.

Piston gauges or pressure balances are important primary standards for the realization of the SI unit of pressure, the pascal. Because of their long-term stability, they are also used as secondary or working standards in the dissemination of the pressure scale. The National Institute of Standards and Technology (NIST) operates and maintains a calibration service for these devices, and has recently undertaken a modernization effort. Following a preliminary investigation into the feasibility of using transducers as instantaneous in-situ transfer standards, we now present the results of a near fully automated calibration system. This effort includes the design, building, and validation of an automated gas-handling manifold, and the development of a new software suite. The new system demonstrates an expanded uncertainty on the order of 1 in 105, comparable to the traditional system, but offers a five-fold decrease in calibration turnaround time.

On-fiber plasmonic interferometer for multi-parameter sensing.

We demonstrate a novel miniature multi-parameter sensing device based on a plasmonic interferometer fabricated on a fiber facet in the optical communication wavelength range. This device enables the coupling between surface plasmon resonance and plasmonic interference in the structure, which are the two essential mechanisms for multi-parameter sensing. We experimentally show that these two mechanisms have distinctive responses to temperature and refractive index, rendering the device the capability of simultaneous temperature and refractive index measurement on an ultra-miniature form factor. A high refractive index sensitivity of 220 nm per refractive index unit (RIU) and a high temperature sensitivity of -60 pm/ °C is achieved with our device.

A capacitive probe for measuring the clearance between the piston and the cylinder of a gas piston gauge.

We used a capacitive technique to determine the radial clearance between the piston and cylinder of a gas piston gauge. This method determines the effective area of a piston gauge pressure standard, independent of calibration against another piston gauge or manometer, as long as the diameter of the piston is dimensionally measured. It also allows an independent determination of piston gauge distortion due to pressure. We have used this technique to measure the clearance and the distortion of six gas piston gauges of the Ruska 2465 type operating in gauge mode. Measurements were made on two gauges each in the low, middle, and high ranges. We describe the capacitance technique and the results of the measurements on the six piston gauges.

A Gas Pressure Scale Based on Primary Standard Piston Gauges.

The National Institute of Standards and Technology (NIST) has redefined its gas pressure scale, up to 17 MPa, based on two primary standard piston gauges. The primary standard piston gauges are 35.8 mm in diameter and operate from 20 kPa to 1 MPa. Ten secondary standard piston gauges, two each of five series of the Ruska 2465 type, with successively smaller diameters form the scale extending up to 17 MPa. Six of the piston gauges were directly compared to the primary standards to determine their effective area and expanded (k = 2) uncertainty. Two piston gauges operating to 7 MPa were compared to the 1.4 MPa gauges, and two piston gauges operating to 17 MPa were compared to the 7 MPa gauges. Distortion in the 7 MPa piston gauges was determined by comparing those gauges to a DH Instruments PG7601 type piston gauge, whose distortion was calculated using elasticity theory. The relative standard uncertainties achieved by the primary standards range from 3.0 × 10(-6) to 3.2 × 10(-6). The relative standard uncertainty of the secondary standards is as low as 4.2 × 10(-6) at 300 kPa. The effective areas and uncertainties were validated by comparison to standards of other National Metrology Institutes (NMIs). Results show agreement in all cases to better than the expanded (k = 2) uncertainty of the difference between NIST and the other NMIs, and in most cases to better than the standard (k = 1) uncertainty of the difference.

Diagnostic performance of rapid diagnostic tests versus blood smears for malaria in US clinical practice.

BACKGROUND: Approximately 4 million US travelers to developing countries are ill enough to seek health care, with 1500 malaria cases reported in the United States annually. The diagnosis of malaria is frequently delayed because of the time required to prepare malaria blood films and lack of technical expertise. An easy, reliable rapid diagnostic test (RDT) with high sensitivity and negative predictive value (NPV), particularly for Plasmodium falciparum, would be clinically useful. The objective of this study was to determine the diagnostic performance of a RDT approved by the US Food and Drug Administration compared with traditional thick and thin blood smears for malaria diagnosis. METHODS: This prospective study tested 852 consecutive blood samples that underwent thick and thin smears and blinded malaria RDTs at 3 hospital laboratories during 2003-2006. Polymerase chain reaction verified positive test results and discordant results. RESULTS: Malaria was noted in 95 (11%) of the 852 samples. The RDT had superior performance than the standard Giemsa thick blood smear (p = .003). The RDT's sensitivity for all malaria was 97% (92 of 95 samples), compared with 85% (81 of 95) for the blood smear, and the RDT had a superior NPV of 99.6%, compared with 98.2% for the blood smear (p = .001). The P. falciparum performance was excellent, with 100% rapid test sensitivity, compared with only 88% (65 of 74) by blood smear (p = .003). CONCLUSIONS: This operational study demonstrates that the US Food and Drug Administration-approved RDT for malaria is superior to a single set of blood smears performed under routine US clinical laboratory conditions. The most valuable clinical role of the RDT is in the rapid diagnosis or the exclusion of P. falciparum malaria, which is particularly useful in outpatient settings when evaluating febrile travelers.

In cerebrospinal fluid ER chaperones ERp57 and calreticulin bind beta-amyloid.

The beta-amyloids (abetas) are the major components of the plaque observed in the brains of patients with Alzheimer's disease. The conundrum is that although they are produced in everyone during the posttranslational processing in the endoplasmic reticulum (ER) of the amyloid precursor protein (APP), deposits are only observed in the elderly. Our work suggests that normals have a carrier protein(s) keeping them in solution. Based on immunoblotting studies of cerebrospinal fluid (CSF) from normals, we find that the bulk of the abetas are bound to the ER chaperones, ERp57 and calreticulin, suggesting that these may be carrier proteins which prevent aggregation of the abetas and that the deposits are due to faulty ER posttranslational processing of APP with the failure to form this complex. If membrane protein synthesis is similarly affected, it could explain the neuronal dysfunction characteristic of Alzheimer's disease.