Comparative Analysis of Gait Speed Estimation Using Wideband and Narrowband Radars, Thermal Camera, and Motion Tracking Suit Technologies.

Research has shown that cognitive and physical functioning of older adults can be reflected in indicators such as walking speed. While changes in cognition, mobility, or health cause changes in gait speed, often gradual variations in walking speed go undetected until severe problems arise. Discrete clinical assessments during clinical consultations often fail to detect changes in day-to-day walking speeds and do not reflect walking speeds in everyday environments, where most of the mobility issues happen. In this paper, we compare four walking speed measurement technologies to a GAITRite mat (gold standard): (1) an ultra wideband radar (covering the band from 3.3 GHz to 10 GHz), (2) a narrow band 24-GHz radar (with a bandwidth of 250 MHz), (3) a perception Neuron Motion Tracking suit, and (4) a thermal camera. Data were collected in parallel using all sensors at the same time for 10 healthy adults for normal and slow walking paces. A comparison of the sensors indicates better performance at lower gait speeds, with offsets (when compared to GAITRite) between 0.1 and 20% for the ultra wideband radar, 1.9 and 17% for the narrowband radar, 0.1 and 38% for the thermal camera, and 1.7 and 38% for the suit. This paper supports the potential of unobtrusive radar-based sensors and thermal camera technologies for ambient autonomous gait speed monitoring for contextual, privacy-preserving monitoring of participants in the community.

Reflux episodes detected by impedance in patients on and off esomeprazole: a randomised double-blinded placebo-controlled crossover study.

BACKGROUND: Combined with 24-h pH monitoring, the use of impedance is the most sensitive method available for detecting oesophageal reflux. Normal values for impedance have been previously established in healthy controls studied on and off proton pump inhibitors (PPI). AIMS: To determine the effects of PPIs on the total number of reflux episodes in the distal oesophagus measured by impedance in patients with and without gastro-oesophageal reflux disease (GERD). METHODS: In this prospective randomised double-blinded placebo controlled crossover study, all patients underwent two 24-h pH with impedance studies at least 2 weeks apart. Based on a randomisation scheme, patients received either 40 mg of esomeprazole twice daily for 1 week or identical capsule placebo for 1 week, then all patients were crossed over to the other treatment arm. GERD was defined by the validated Johnson-DeMeester score. Reflux by impedance was defined as a 50% decrease from baseline in retrograde movement of liquid between two impedance sites. RESULTS: Sixty-three patients were enrolled and 41 patients completed the study [mean age 52 ± 12 years, 42% (17/41) men, 56% (23/41) Caucasian and 34% (14/41) African American]. Overall, there was no significant decrease in the total number of distal impedance episodes with esomeprazole compared with placebo (mean change 6.1 ± 22, P = 0.100). When analysed separately by GERD status, among GERD-positive patients, there was a significant decrease in distal impedance episodes while on esomeprazole compared with placebo (mean change -16 ± 22, P = 0.023), but not in GERD-negative patients (mean change -0.35 ± 20, P = 0.872). CONCLUSION: Esomeprazole decreases significantly the number of reflux episodes detected by impedance, but only in patients with GERD.

Confocal microscopy of unfixed breast needle core biopsies: a comparison to fixed and stained sections.

BACKGROUND: Needle core biopsy, often in conjunction with ultrasonic or stereotactic guided techniques, is frequently used to diagnose breast carcinoma in women. Confocal scanning laser microscopy (CSLM) is a technology that provides real-time digital images of tissues with cellular resolution. This paper reports the progress in developing techniques to rapidly screen needle core breast biopsy and surgical specimens at the point of care. CSLM requires minimal tissue processing and has the potential to reduce the time from excision to diagnosis. Following imaging, specimens can still be submitted for standard histopathological preparation. METHODS: Needle core breast specimens from 49 patients were imaged at the time of biopsy. These lesions had been characterized under the Breast Imaging Reporting And Data System (BI-RADS) as category 3, 4 or 5. The core biopsies were imaged with the CSLM before fixation. Samples were treated with 5% citric acid and glycerin USP to enhance nuclear visibility in the reflectance confocal images. Immediately following imaging, the specimens were fixed in buffered formalin and submitted for histological processing and pathological diagnosis. CSLM images were then compared to the standard histology. RESULTS: The pathologic diagnoses by standard histology were 7 invasive ductal carcinomas, 2 invasive lobular carcinomas, 3 ductal carcinomas in-situ (CIS), 21 fibrocystic changes/proliferative conditions, 9 fibroadenomas, and 5 other/benign; two were excluded due to imaging difficulties. Morphologic and cellular features of benign and cancerous lesions were identified in the confocal images and were comparable to standard histologic sections of the same tissue. CONCLUSION: CSLM is a technique with the potential to screen needle core biopsy specimens in real-time. The confocal images contained sufficient information to identify stromal reactions such as fibrosis and cellular proliferations such as intra-ductal and infiltrating carcinoma, and were comparable to standard histologic sections of the same tissue. Morphologic and cellular features of benign and cancerous lesions were identified in the confocal images. Additional studies are needed to 1.) establish correlation of the confocal and traditional histologic images for the various diseases of the breast; 2.) validate diagnostic use of CSLM and; 3.) further define features of borderline lesions such as well-differentiated ductal CIS vs. atypical hyperplasia.

In vivo confocal microscopy of Meissner corpuscles as a measure of sensory neuropathy.

OBJECTIVE: To assess feasibility of noninvasive in vivo reflectance confocal microscopy (RCM) of Meissner corpuscles (MCs) as a measure of sensory neuropathy (SN). BACKGROUND: MCs are touch-pressure sensation receptors in glabrous skin. Skin biopsy studies suggest that fingertip MC density (MCs/mm(2)) is a sensitive measure of diabetic and idiopathic SN. In vivo RCM of skin is an emerging field, with applications including evaluation of cancer. It is painless and noninvasive. Feasibility of in vivo RCM of MCs has not been explored. METHODS: Fifteen adults (10 controls, 5 SN subjects) underwent in vivo RCM at the fingertip (Digit V) and thenar eminence. In vivo RCM was conducted to determine whether MCs were visible within dermal papillae and, if visible, to characterize their imaging appearance and assess MCs/mm(2) at each site. RESULTS: MCs were identified in dermal papillae at all sites in controls. MCs appeared as heterogeneous bright structures within dermal papillae, which appeared as dark "pits." Mean MC density in controls was 12 +/- 5.3/mm(2) (Digit V) and 5.1 +/- 2.2/mm(2) at the thenar eminence. MC density in SN was lower than controls at Digit V (2.8 +/- 5.7/mm(2), p = 0.01) and the thenar eminence (1.4 +/- 1.1/mm(2), p = 0.004). MCs were absent in a sensory neuronopathy; milder reductions in MC density were seen among diabetic and HIV-positive subjects. CONCLUSIONS: Meissner corpuscles (MCs) can be visualized and quantitated in controls and sensory neuropathy (SN) using in vivo reflectance confocal microscopy (RCM). In vivo RCM of MCs has potential for noninvasive detection and monitoring of SN, if subsequent studies show that with denervation or reinnervation, reliable and recognizable changes or loss can be detected using our described approaches.

Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino Observatory with enhanced neutral current sensitivity.

The Sudbury Neutrino Observatory has precisely determined the total active (nu(x)) 8B solar neutrino flux without assumptions about the energy dependence of the nu(e) survival probability. The measurements were made with dissolved NaCl in heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27(stat)+/-0.38(syst) x 10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Deltam(2)=7.1(+1.2)(-0.6) x 10(-5) eV(2) and theta=32.5(+2.4)(-2.3) degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.

Constraints on nucleon decay via invisible modes from the Sudbury Neutrino Observatory.

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to "invisible" modes, such as n-->3nu. The analysis was based on a search for gamma rays from the deexcitation of the residual nucleus that would result from the disappearance of either a proton or neutron from 16O. A limit of tau(inv)>2 x 10(29) yr is obtained at 90% confidence for either neutron- or proton-decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton-decay modes and 400 times more stringent than similar neutron modes.

Direct evidence for neutrino flavor transformation from neutral-current interactions in the Sudbury Neutrino Observatory.

Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.

Measurement of day and night neutrino energy spectra at SNO and constraints on neutrino mixing parameters.

The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is 14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.

Measurement of the rate of nu(e) + d --> p + p + e(-) interactions produced by (8)B solar neutrinos at the Sudbury Neutrino Observatory.

Solar neutrinos from (8)B decay have been detected at the Sudbury Neutrino Observatory via the charged current (CC) reaction on deuterium and the elastic scattering (ES) of electrons. The flux of nu(e)'s is measured by the CC reaction rate to be straight phi(CC)(nu(e)) = 1.75 +/- 0.07(stat)(+0.12)(-0.11)(syst) +/- 0.05(theor) x 10(6) cm(-2) s(-1). Comparison of straight phi(CC)(nu(e)) to the Super-Kamiokande Collaboration's precision value of the flux inferred from the ES reaction yields a 3.3 sigma difference, assuming the systematic uncertainties are normally distributed, providing evidence of an active non- nu(e) component in the solar flux. The total flux of active 8B neutrinos is determined to be 5.44+/-0.99 x 10(6) cm(-2) s(-1).

Pupil-plane speckle imaging with a referenced polarization technique.

Pupil-plane speckle imaging is demonstrated by use of a polarimeter to estimate the complex wave front from an actively illuminated target. An experimental technique, referenced polarization imaging (RPI), closely parallels optical heterodyne imaging but is easier to perform in a laboratory. Further, RPI is less sensitive to target motions than the heterodyne method. The RPI technique is described, along with experimental results.

Double-exposure heterodyne imaging for observing line-of-sight deformation.

An optical heterodyne array imaging system is described for double-exposure interferometric measurement of objects that change because of stress or vibration. The signal measurement and processing approach is summarized, and the method is demonstrated in the laboratory. An advantage of this technique over other electronic interferometric imaging methods is that complex exposures are created with digital phase and amplitude values at each image pixel. In addition, measurement of object deformation does not require time synchronization between the camera exposure time, or laser pulse time, and object vibration frequency.

Infusion therapy with milrinone in the home care setting for patients who have advanced heart failure.

Advanced heart failure (AHF) is a serious cause of mortality and morbidity in the United States. The treatment of AHF exacts a great financial and manpower toll on the healthcare infrastructure. The quality of life of patients with AHF also is reduced severely. When it is infused at home, Milrinone, which is an intravenous inodilator agent, reduces the number of hospitalizations. Milrinone decreases the overall treatment costs of AHF. Highly skilled home nursing care is required in the treatment of patients. The home care nurse plays a major role in the outcome of a patient with AHF.

Laboratory validation of range-resolved reflective tomography signal-to-noise expressions.

The Air Force Phillips Laboratory is in the process of demonstrating an advanced space surveillance capability with a heterodyne laser radar (ladar) system. Notable features of this ladar system include its narrow micropulses (<1.5 ns) contained in a pulse-burst wave form that allows high-resolution range data to be obtained and its high power (30 J/pulse burst) that permits reasonable signal returns from satellites. Recently, time-resolved image-domain signal-to-noise ratios have been derived for both the intensity projections calculated from the range-resolved reflective data and image information obtained with linear combinations of the projections. In this paper the signal-to-noise expression for intensity projections is validated by laboratory data.

Cellular and biochemical characterization of VX-710 as a chemosensitizer: reversal of P-glycoprotein-mediated multidrug resistance in vitro.

VX-710 or (S)-N[2-Oxo-2-(3,4,5-trimethoxyphenyl)acetyl]-piperidine-2-carboxylic acid 1,7-bis(3-pyridyl)-4-heptyl ester, a novel non-macrocyclic ligand of the FK506-binding protein FKBP12, was evaluated for its ability to reverse P-glycoprotein-mediated multidrug resistance in vitro. VX-710 at 0.5-5 microM restored sensitivity of a variety of multidrug resistant cells to the cytotoxic action of doxorubicin, vincristine, etoposide or paclitaxel, including drug-selected human myeloma and epithelial carcinoma cells, and human MDR1 cDNA-transfected mouse leukemia and fibroblast cells. Uptake experiments showed that VX-710 at 0.5-2.5 microM fully restored intracellular accumulation of [14C]doxorubicin in multidrug resistant cells, suggesting that VX-710 inhibits the drug efflux activity of P-glycoprotein. VX-710 effectively inhibited photoaffinity labeling of P-glycoprotein by [3H]azidopine or [125I]iodoaryl azidoprazosin with EC50 values of 0.75 and 0.55 microM. Moreover, P-glycoprotein was specifically labeled by a tritiated photoaffinity analog of VX-710 and unlabeled VX-710 inhibited analog binding with an EC50 of 0.75 microM. VX-710 also stimulated the vanadate-inhibitable P-glycoprotein ATPase activity 2- to 3-fold in a concentration-dependent manner with an apparent k(a) of 0.1 microM. These data indicate that a direct, high-affinity interaction of VX-710 with P-glycoprotein prevents efflux of cytotoxic drugs by the MDR1 gene product in multidrug resistant tumor cells.

Comparative X-ray structures of the major binding protein for the immunosuppressant FK506 (tacrolimus) in unliganded form and in complex with FK506 and rapamycin.

FK506 (tacrolimus) is a natural product now approved in the US and Japan for organ transplantation. FK506, in complex with its 12 kDa cytosolic receptor (FKBP12), is a potent agonist of immunosuppression through the inhibition of the phosphatase activity of calcineurin. Rapamycin (sirolimus), which is itself an immunosuppressant by a different mechanism, completes with FK506 for binding to FKBP12 and thereby acts as an antagonist of calcineurin inhibition. We have solved the X-ray structure of unliganded FKBP12 and of FKBP12 in complex with FK506 and with rapamycin; these structures show localized differences in conformation and mobility in those regions of the protein that are known, by site-directed mutagenesis, to be involved in calcineurin inhibition. A comparison of 16 additional X-ray structures of FKBP12 in complex with FKBP12-binding ligands, where those structures were determined from different crystal forms with distinct packing arrangements, lends significance to the observed structural variability and suggests that it represents an intrinsic functional characteristic of the protein. Similar differences have been observed for FKBP12 before, but were considered artifacts of crystal-packing interactions. We suggest that immunosuppressive ligands express their differential effects in part by modulating the conformation of FKBP12, in agreement with mutagenesis experiments on the protein, and not simply through differences in the ligand structures themselves.