Johnson Noise Thermometry.

Johnson noise thermometers infer thermodynamic temperature from measurements of the thermally-induced current fluctuations that occur in all electrical conductors. This paper reviews the status of Johnson noise thermometry and its prospects for both metrological measurements and for practical applications in industry. The review begins with a brief description of the foundations and principles of Johnson noise thermometry before outlining the many different techniques and technological breakthroughs that have enabled the application of JNT to high-accuracy, cryogenic, and industrial thermometry. Finally, the future of noise thermometry is considered. As the only purely electronic approach to thermodynamic temperature measurement, Johnson noise thermometry has appeal for metrological applications at temperatures ranging from below 1 µK up to 800 K. With the rapid advances in digital technologies, there are also expectations that noise thermometry will become a practical option for some industrial applications reaching temperatures above 2000 K.

A Boltzmann Constant Determination Based on Johnson Noise Thermometry.

A value for the Boltzmann constant was measured electronically using an improved version of the Johnson Noise Thermometry (JNT) system at the National Institute of Standards and Technology (NIST), USA. This system is different from prior ones, including those from the 2011 determination at NIST and both 2015 and 2017 determinations at the National Institute of Metrology (NIM), China. As in all three previous determinations, the main contribution to the combined uncertainty is the statistical uncertainty in the noise measurement, which is mitigated by accumulating and integrating many weeks of cross-correlated measured data. The second major uncertainty contribution also still results from variations in the frequency response of the ratio of the measured spectral noise of the two noise sources, the sense resistor at the triple-point of water and the superconducting quantum voltage noise source. In this paper, we briefly describe the major differences between our JNT system and previous systems, in particular the input circuit and approach we used to match the frequency responses of the two noise sources. After analyzing and integrating 49 days of accumulated data, we determined a value: k = 1.380 642 9(69)×10-23 J/K with a relative standard uncertainty of 5.0×10-6 and relative offset -4.05×10-6 from the CODATA 2014 recommended value.

Systematic evaluation of an atomic clock at 2 × 10(-18) total uncertainty.

The pursuit of better atomic clocks has advanced many research areas, providing better quantum state control, new insights in quantum science, tighter limits on fundamental constant variation and improved tests of relativity. The record for the best stability and accuracy is currently held by optical lattice clocks. Here we take an important step towards realizing the full potential of a many-particle clock with a state-of-the-art stable laser. Our (87)Sr optical lattice clock now achieves fractional stability of 2.2 × 10(-16) at 1 s. With this improved stability, we perform a new accuracy evaluation of our clock, reducing many systematic uncertainties that limited our previous measurements, such as those in the lattice ac Stark shift, the atoms' thermal environment and the atomic response to room-temperature blackbody radiation. Our combined measurements have reduced the total uncertainty of the JILA Sr clock to 2.1 × 10(-18) in fractional frequency units.

Treatment and trials: ovarian cancer in older women.

Ovarian cancer (OC) is a disease of elderly women. The disease spreads insidiously and presents at an advanced stage at initial diagnosis for most patients. Several groups reported at least a two-fold increased risk of death in women older than 65. Various theories have been proposed to explain this survival disparity in older women, including: (1) more aggressive cancer with advanced age, (2) inherent resistance to chemotherapy, (3) individual patient factors such as multiple concurrent medical problems, and (4) physician and health-care biases toward the elderly that lead to inadequate surgery, less than optimal chemotherapy, and poor enrollment in clinical trials. As a result of this high clinical variability, oncologists need to be more familiar with the comprehensive geriatric assessment to better identify vulnerable patients at higher risk of complications. Several geriatric tools are available to assess the physiologic and functional capacities of older patients and to better individualize treatment. This paper gives an overview of the management of elderly patients with OC, in particular the integration of chemotherapy, surgery, and geriatric assessment to improve treatment tolerance and survival outcomes.

A phase 2 trial of oral imatinib in patients with epithelial ovarian, fallopian tube, or peritoneal carcinoma in second or greater remission.

PURPOSE OF INVESTIGATION: To determine the effect of imatinib on progression-free survival in patients with epithelial ovarian cancer in second or greater complete clinical remission (CCR). METHODS: 35 patients were enrolled between 10/2002 and 1/2005. Eligible patients received imatinib at 400 mg daily orally. RESULTS: One patient withdrew consent, and two patients received protocol therapy in first remission and were excluded. Five patients were removed for possibly related toxicity. No associations were seen between PDGF-R staining and PFS. CONCLUSIONS: Treatment with imatinib for patients with ovarian cancer in second CCR or greater did not prolong the PFS beyond the historical estimate.

The Kelvin and Temperature Measurements.

The International Temperature Scale of 1990 (ITS-90) is defined from 0.65 K upwards to the highest temperature measurable by spectral radiation thermometry, the radiation thermometry being based on the Planck radiation law. When it was developed, the ITS-90 represented thermodynamic temperatures as closely as possible. Part I of this paper describes the realization of contact thermometry up to 1234.93 K, the temperature range in which the ITS-90 is defined in terms of calibration of thermometers at 15 fixed points and vapor pressure/temperature relations which are phase equilibrium states of pure substances. The realization is accomplished by using fixed-point devices, containing samples of the highest available purity, and suitable temperature-controlled environments. All components are constructed to achieve the defining equilibrium states of the samples for the calibration of thermometers. The high quality of the temperature realization and measurements is well documented. Various research efforts are described, including research to improve the uncertainty in thermodynamic temperatures by measuring the velocity of sound in gas up to 800 K, research in applying noise thermometry techniques, and research on thermocouples. Thermometer calibration services and high-purity samples and devices suitable for "on-site" thermometer calibration that are available to the thermometry community are described. Part II of the paper describes the realization of temperature above 1234.93 K for which the ITS-90 is defined in terms of the calibration of spectroradiometers using reference blackbody sources that are at the temperature of the equilibrium liquid-solid phase transition of pure silver, gold, or copper. The realization of temperature from absolute spectral or total radiometry over the temperature range from about 60 K to 3000 K is also described. The dissemination of the temperature scale using radiation thermometry from NIST to the customer is achieved by calibration of blackbody sources, tungsten-strip lamps, and pyrometers. As an example of the research efforts in absolute radiometry, which impacts the NIST spectral irradiance and radiance scales, results with filter radiometers and a high-temperature blackbody are summarized.

Periarticular heterotopic ossification after multiple knee ligament reconstructions. A report of three cases.

Heterotopic ossification is a frequently encountered clinical and radiographic entity. There are no previous reports in the English literature of heterotopic ossification after arthroscopically assisted ligament reconstructions for knee dislocations. Further, a link between the PCL reconstruction and posterior capsular ossification has not been heretofore recognized. Our three cases should raise the clinical awareness of such an entity.

Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia.

Brain structural deviation is known to be present in chronic patients with schizophrenia when compared with normal age-matched individuals. While the assumption is that these differences are based on a neurodevelopmental disturbance, whether they are static or continue to change throughout the disease process remains unknown. The following report describes a prospective follow-up study of first episode cases of schizophrenic illness. Analyses of MRI evaluations on an approximate annual basis for a minimum of four years are presented on 50 patients and 20 controls. Computer-assisted image analysis measuring the volume of several brain regions, using the program ANALYZE (Mayo Clinic), was performed on all scans. Patients were compared with controls for the rate of change over time in size of structures. No differences were found for the volumes of the caudate nucleus, temporal lobes, or hippocampus; and no changes in the degree of cerebral laterality were detected. However, there was a significant difference in the rate of change in the overall volumes of left and right hemispheres (P < 0.0004 and 0.001, respectively), right cerebellum (P < 0.02) and area of the isthmus of the corpus callosum (P < 0.05). The left cerebral ventricle had significantly greater enlargement over time when measured on coronal slice sequences (P < 0.02), but was not detected by axial views. These findings suggest that a subtle active brain process may be continuing through the first few years of a schizophrenic illness causing greater than the normal adult cortical deterioration. Further studies using other methods of image analysis and over a longer period of time are needed to determine the course and nature of this biologic process.

Cortical gray matter volume deficit in patients with first-episode schizophrenia.

OBJECTIVE: A cortical gray matter deficit has been found in cross-sectional studies of patients with chronic schizophrenia. The purpose of this study was to examine whether this deficit is present early in the course of illness. METHOD: The authors measured cortical gray matter volume on magnetic resonance images acquired within 6 months of onset of illness from 22 patients with first-episode schizophrenia and 51 age-matched comparison subjects from the Stony Brook First Episode Study. RESULTS: A significant cortical gray matter deficit and lateral ventricular enlargement were found in schizophrenic patients relative to the comparison group. CONCLUSIONS: The presence of the cortical gray matter deficit close to onset of illness supports the role of preexisting structural brain deficits in the genesis of schizophrenia.

A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings.

Brain morphological abnormalities have been reported in several independent investigations of chronic schizophrenic patients. The present study is a prospective 4-year follow-up of first-episode schizophrenic patients to determine whether some of these abnormalities may be a consequence of regional brain structural change over time after the onset of a first psychotic episode. Whole hemisphere, temporal lobes, superior temporal gyrus, hippocampus, caudate, corpus callosum, and lateral ventricles were measured in a series of MRI scans taken over a 4-year period in 20 patients and five controls. Total volume reduction was noted in both hemispheres to a greater degree in patients than controls. When adjusted for total brain size, left ventricular enlargement occurred in patients, but not controls, over time. These preliminary data suggest that subtle cortical atrophy may be occurring over time after the onset of illness.

In vitro analysis of proximal femoral strains using PCA femoral implants and a hip-abductor muscle simulator.

The strains produced in the proximal femur by noncemented and cemented PCA femoral implants have been compared to each other and to the strains in the same intact femur. The effect on the strain pattern of a hip-abductor muscle simulator was also tested. Nine embalmed femora were tested; two were used for development of the protocol, one was covered with a reflective photoelastic coating, and six were instrumented with eight strain gauge rosettes on each femur. For a given body weight on the photoelastically coated intact bone, the abductor-simulator increased the mean shear strains on both the medial (132%) and lateral (153%) aspects, with standard deviations of 13% and 20%, respectively; however, no strain-concentrated areas were observed. With an abductor simulator on the strain-gauged femurs, calcar shear strains were significantly reduced (P less than .01), from those on the intact bone, by both noncemented and cemented implants. These reductions were 74.2% and 91.8%, respectively, with no significant difference between the two techniques. Reductions in shear strain were noted at midstem on the medial side for the noncemented (20.5%) and cemented (35.9%) implants; however, only the cemented implants produced significantly less (P less than .05) strain than the intact bone at this location. At midstem on the medial aspect of the femur, there was a significant difference (P less than .05) between the data for the cemented and noncemented implants. Analysis of variance identified no other regions of significant change.

Glutaraldehyde-preserved venous valve transplantation in the dog.

Transplantation of femoral vein grafts was performed on 33 mongrel dogs to assess graft patency and valvular function after storage in glutaraldehyde. The grafts were removed from the donor, flushed with room temperature heparinized lactated Ringer's solution, and then stored in a 0.2% glutaraldehyde solution for 16 hr. At the time of grafting, the veins were again flushed with lactated Ringer's and anastomosed orthotopically to the recipient. An arteriovenous fistula was also created. Postoperatively the animals received daily doses of aspirin (2 mg/kg) and dipyridamol (50 mg). The following groups were studied: Group I (n = 10) served as controls and received fresh autografts. Group II (n = 13) received autografts stored for 16 hr in 0.2% glutaraldehyde. Group III (n = 10) received allografts stored similarly in glutaraldehyde for 16 hr. The grafts were monitored for evidence of patency. All grafts were removed for histological evaluation when patency was no longer detected or at the end of 7 weeks. Of the fresh and glutaraldehyde-preserved autografts (Group 1), 100% were patent at 7 weeks, and generally retained valve function. Patency of allografts was only slightly inferior but valve function was disappointingly poor at 7 weeks.

Relative molecular weight and concentration determination of sodium hyaluronate solutions by gel-exclusion high-performance liquid chromatography.

Gel-exclusion chromatography coupled with HPLC instrumentation can be used to determine the molecular weight of highly purified sodium hyaluronate in solution. The method is very reproducible, precise, and rapid, and allows molecular weight determinations up to 2 million to be done in the presence of considerable impurities. This technique offers considerable advantages over traditional light-scattering, sedimentation equilibrium, and viscometry methods for molecular weight determinations, in that HPLC-gel exclusion is rapid and not subject to errors arising from impurities. Simultaneous with molecular weight measurements, sodium hyaluronate concentrations can be determined with a lower range of 0.1 to 0.3 mg/ml dependent upon the sensitivity of the refractive index-detecting system. Unlike the carbazole reaction, this technique is unaffected by low-molecular-weight impurities such as monosaccharides or substances with relative molecular weights less than 18,000.

Cartilaginous debris in the injured human knee. Correlation with arthroscopic findings.

Cytologic analysis of filtered synovial lavage was compared with the independent arthroscopic findings in 70 patients with knee pain secondary to injury. Correlation existed between the arthroscopic evaluation of the articular surfaces and the presence of cartilaginous fragments and their microscopic features. Study of the filtered lavage was carried out without knowledge of the patient's clinical status or arthroscopic findings. Patients with unblemished articular surfaces and normal menisci demonstrated essentially no fragments in the synovial lavage. Minimal fibrillation of the articular surface with normal menisci was associated with few cartilage fragments per sample. Patients with moderate to severe fibrillation of the articular surface requiring a surface altering procedure, demonstrated significantly more fragments per sample. Chondrocyte nuclei were visible in these fragments, often arranged in multicellular clusters. Isolated lesions of the meniscus were associated with cartilage fragments that did not contain chondrocyte nuclei. Microscopic analysis of synovial lavage may serve as a useful diagnostic adjunct in the evaluation of the painful knee and the study of the pathogenic role of cartilage fragments is osteoarthrosis.

Prevention of phosphate-induced progression of uremia in rats by 3-phosphocitric acid.

Male Sprague-Dawley rats were rendered uremic by surgical removal of 70% of functioning renal mass. This produced a rapid threefold rise in serum creatinine to 0.87 +/- 0.067 (SEM) mg/dl at 2 weeks postoperatively which declined subsequently to a value of 0.64 +/- 0.06 (SEM) and remained stable thereafter for an additional 4 weeks in animals maintained on a diet with normal phosphate content. Increase of dietary phosphate content to 2.2% at 2 weeks after surgery produced a significant and progressive increase in serum creatinine to values fourfold higher than the mean values in comparable partially nephrectomized control animals maintained on a diet with normal phosphate content (P less than 0.001). This deterioration in renal function was associated with extensive nephrocalcinosis, tubular dilatation, cellular necrosis, and marked interstitial inflammation. 3-phosphocitric acid, a compound which has been shown to prevent calcium phosphate crystal growth as well as to prevent in vivo nephrocalcinosis, was very effective in preventing this phosphate-induced deterioration of renal function and in preventing any significant increase in renal calcium content in animals fed a high phosphate diet. This compound was also effective in preventing the renal histologic changes associated with phosphate-induced uremia.

Identification of cartilage wear fragments in synovial fluid from equine joints.

Synovial fluids from 72 equine joints were examined for the presence of cartilage debris, and these findings were compared to findings from visual inspection of the articular cartilage surfaces at necropsy. Synovial fluids from 25 joints with visual cartilage damage contained one or more large particles of articular cartilage. Cartilage fragments were not found in synovial fluids from 42 of the 47 apparently normal joints; thus, a correlation may exist between cartilage debris in the synovial fluid and lesions of the articular surfaces.

Phosphocitrate inhibits mitochondrial and cytosolic accumulation of calcium in kidney cells in vivo.

Synthetic 3-phosphocitrate, an extremely potent inhibitor of calcium phosphate crystallization as determined in a nonbiological physical-chemical assay, has many similarities to a mitochondrial factor that inhibits crystallization of nondiffracting amorphous calcium phosphate. In order to determine whether phosphocitrate can prevent uptake and crystallization of calcium phosphate in mitochondria in vivo, it was administered intraperitoneally to animals given large daily doses of calcium gluconate or parathyroid hormone, a regimen that causes massive accumulation and crystallization of calcium phosphate in the mitochondria and cytosol of renal tubule cells in vivo. Administration of phosphocitrate greatly reduced the net uptake of Ca2+ by the kidneys and prevented the appearance of apatite-like crystalline structures within the mitochondrial matrix and cytosol of renal tubule cells. Phosphocitrate, which is a poor chelator of Ca2+, did not reduce the hypercalcemia induced by either agent. These in vivo observations therefore indicate that phosphocitrate acts primarily at the cellular level to prevent the extensive accumulation of calcium phosphate in kidney cells by inhibiting the mitochondrial accumulation or crystallization of calcium phosphate.