Cryogenic probe for low-noise, high-frequency electronic measurements.

The design and performance of a low-noise, modular cryogenic probe, which is applicable to a wide range of measurements over a broad range of working frequencies, temperatures, and magnetic fields, is presented. The design of the probe facilitates the exchange of sample holders and sample-stage amplifiers, which, combined with its characteristic low transmission and reflection loss, make this design suitable for high precision or low sensitivity measurements. The specific example of measuring the shot noise of magnetic tunnel junctions is discussed. We highlight various design characteristics chosen specifically to expand the applicability of the probe to measurement techniques such as nuclear magnetic resonance.

Neural Network Repair of Lossy Compression Artifacts in the September 2015 to March 2016 Duration of the MMS/FPI Data Set.

During the September 2015 to March 2016 duration (sometimes referred to as Phase 1A) of the Magnetospheric Multiscale Mission, the Dual Electron Spectrometers (DES) were configured to generously utilize lossy compression. While this maximized the number of velocity distribution functions downlinked, it came at the expense of lost information content for a fraction of the frames. Following this period of lossy compression, the DES was reconfigured in a way that allowed for 95% of the frames to arrive to the ground without loss. Using this high-quality set of frames from on-orbit observations, we compressed and decompressed the frames on the ground to create a side-by-side record of the compression effect. This record was used to drive an optimization method that (a) derived basis functions capable of approximating the lossless sample space and with nonnegative coefficients and (b) fitted a function which maps the lossy frames to basis weights that recreate the frame without compression artifacts. This method is introduced and evaluated in this paper. Data users should expect a higher level of confidence in the absolute scale of density/temperature measurements and notice less sinusoidal bias in the velocity X and Y components (GSE).

Factors affecting estimates of size at age and growth in grey triggerfish Balistes capriscus from the northern Gulf of Mexico.

Growth zones in dorsal spines of grey triggerfish Balistes capriscus from the northern Gulf of Mexico were utilized to estimate growth and examine factors that may affect estimates of size at age. Age was estimated from dorsal-spine sections of 4687 individuals sampled from U.S. waters during 2003-2013, including both fishery-independent (n = 1312) and fishery-dependent (n = 3375) samples. Ninety-six per cent (n = 4498) of these sections were deemed suitable for ageing; average per cent error between two independent readers was 10·8%. Fork length (LF ) ranged from 65 to 697 mm and age estimates from 0 to 14 years. Both sex and sample source (fishery-independent v. recreational) significantly affected estimated size at age for 2-6 year-old fish. Data were pooled between sources to fit sex-specific von Bertalanffy growth functions. Results for the female model were L∞ = 387 mm LF , k = 0·52 year-1 and t0 = 0·01 year, while for males L∞ = 405 mm LF , k = 0·55 year-1 and t0 = 0·02 year. These results were significantly different between sexes and indicate clear sexual dimorphism. Thus, growth should be modelled separately by sex when examining population parameters or conducting stock assessment modelling. The positive bias in estimates of size at age computed for recreational v. fishery-independent samples also has clear implications for stock assessment as growth functions computed with fishery-dependent samples would tend to overestimate stock productivity.

Natural variability and effects of cleaning and storage procedures on vertebral chemistry of the blacktip shark Carcharhinus limbatus.

Key methodological assumptions regarding the degree of natural variability and influence of sample handling and storage of elasmobranch vertebral chemistry were assessed using laser-ablation inductively coupled plasma mass spectrometry. Vertebral chemistry of juvenile blacktip sharks Carcharhinus limbatus was examined to identify whether differences existed among different regions of the vertebral column, between thoracic vertebrae of individual fish or within individual vertebrae. Additionally, the effects of bleach exposure and storage in ethanol on vertebral chemistry were compared. No significant variation in vertebral chemistry was found among different regions of the vertebral column or between thoracic vertebrae, but significant differences among transect locations within individual vertebrae were observed. The variation at all three levels appears comparable with published data on sagittal otoliths of bilaterally symmetrical teleost fishes. The experimental assessment of potential treatment effects indicated vertebral chemistry was not significantly affected by bleach or exposure to ethanol. Taken together, these results support the idea that vertebrae taken from the same region of the vertebral column can be treated as equivalent and at least certain elements remain robust to exposure to bleach and ethanol.

A magneto-optical microscope for quantitative measurement of magnetic microstructures.

An optical system is presented to quantitatively map the stray magnetic fields of microscale magnetic structures, with field resolution down to 50 µT and spatial resolution down to 4 µm. The system uses a magneto-optical indicator film (MOIF) in conjunction with an upright reflective polarizing light microscope to generate optical images of the magnetic field perpendicular to the image plane. A novel single light path construction and discrete multi-image polarimetry processing method are used to extract quantitative areal field measurements from the optical images. The integrated system including the equipment, image analysis software, and experimental methods are described. MOIFs with three different magnetic field ranges are calibrated, and the entire system is validated by measurement of the field patterns from two calibration samples.

A phase I study to determine the safety, tolerability and maximum tolerated dose of green-lipped mussel (Perna canaliculus) lipid extract, in patients with advanced prostate and breast cancer.

BACKGROUND: This was a phase I trial to determine the maximum tolerated dose (MTD) of a marine lipid extract from the New Zealand green-lipped mussel (Perna canaliculus), as an inhibitor of 5- and 12-lipo-oxygenase enzymes, in patients with advanced breast and prostate cancers. PATIENTS AND METHODS: This was an open-labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily schedule, orally. Patients remained on study until disease progression or unacceptable toxicity. RESULTS: From December 1999 to May 2003, 17 patients were enrolled. Fifteen of them were male with advanced prostate cancer and two were female with advanced breast cancer. The median age of the patients was 74 years (range 56-85 years). Sixteen patients were assessable for adverse events and dose-limiting toxicity (DLT). Reason for withdrawal from the study included progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no objective tumour responses noted. CONCLUSIONS: GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.

Active microelectronic neurosensor arrays for implantable brain communication interfaces.

We have built a wireless implantable microelectronic device for transmitting cortical signals transcutaneously. The device is aimed at interfacing a cortical microelectrode array to an external computer for neural control applications. Our implantable microsystem enables 16-channel broadband neural recording in a nonhuman primate brain by converting these signals to a digital stream of infrared light pulses for transmission through the skin. The implantable unit employs a flexible polymer substrate onto which we have integrated ultra-low power amplification with analog multiplexing, an analog-to-digital converter, a low power digital controller chip, and infrared telemetry. The scalable 16-channel microsystem can employ any of several modalities of power supply, including radio frequency by induction, or infrared light via photovoltaic conversion. As of the time of this report, the implant has been tested as a subchronic unit in nonhuman primates ( approximately 1 month), yielding robust spike and broadband neural data on all available channels.

Oxygen isotope analysis of phosphate: improved precision using TC/EA CF-IRMS.

Oxygen isotope values of biogenic apatite have long demonstrated considerable promise for paleothermometry potential because of the abundance of material in the fossil record and greater resistance of apatite to diagenesis compared to carbonate. Unfortunately, this promise has not been fully realized because of relatively poor precision of isotopic measurements, and exceedingly small size of some substrates for analysis. Building on previous work, we demonstrate that it is possible to improve precision of delta18O(PO4) measurements using a 'reverse-plumbed' thermal conversion elemental analyzer (TC/EA) coupled to a continuous flow isotope ratio mass spectrometer (CF-IRMS) via a helium stream [Correction made here after initial online publication]. This modification to the flow of helium through the TC/EA, and careful location of the packing of glassy carbon fragments relative to the hot spot in the reactor, leads to narrower, more symmetrically distributed CO elution peaks with diminished tailing. In addition, we describe our apatite purification chemistry that uses nitric acid and cation exchange resin. Purification chemistry is optimized for processing small samples, minimizing isotopic fractionation of PO4(-3) and permitting Ca, Sr and Nd to be eluted and purified further for the measurement of delta44Ca and 87Sr/86Sr in modern biogenic apatite and 143Nd/144Nd in fossil apatite. Our methodology yields an external precision of +/- 0.15 per thousand (1sigma) for delta18O(PO4). The uncertainty is related to the preparation of the Ag3PO4 salt, conversion to CO gas in a reversed-plumbed TC/EA, analysis of oxygen isotopes using a CF-IRMS, and uncertainty in constructing calibration lines that convert raw delta18O data to the VSMOW scale. Matrix matching of samples and standards for the purpose of calibration to the VSMOW scale was determined to be unnecessary. Our method requires only slightly modified equipment that is widely available. This fact, and the demonstrated improvement in precision, should help to make apatite paleothermometry far more accessible to paleoclimate researchers.

Management and survival trends in advanced colorectal cancer.

AIMS: Significant improvements in the outcome for patients with advanced colorectal cancer (CRC) have been achieved. The median survival for advanced CRC reported in clinical trials now approaches 2 years, but there is often a question as to whether this partly represents patient selection. We aimed to explore whether the availability of new chemotherapy drugs (irinotecan and oxaliplatin) and surgical advances have affected survival in a normal clinical setting. MATERIALS AND METHODS: A review of the Queen Elizabeth and Lyell McEwin health service prospective CRC database from 1992 to 2004 was carried out to assess outcome differences between two time cohorts (1 January 1992-31 December 1997 and 1 January 1998-31 December 2004). RESULTS: For all patients (n = 744) overall survival was seen to improve over time and is maintained out to 5 years. There have been a number of trends over time (1992-1997 vs 1998-2004) that have probably contributed to this gain; increased overall chemotherapy use (33% vs 43%); use of combination chemotherapy (i.e. oxaliplatin and irinotecan regimens); increased hepatic resection rates (1.9% vs 10.8%) and increased clinical trial uptake (0.6% vs 14.5%). CONCLUSION: This current analysis confirms an improvement in survival over time for advanced CRC and this is seen in unselected patients including those over 70 years of age.

Determination of dosimetric perturbations caused by aneurysm clip in stereotactic radiosurgery using gel phantoms and EBT-Gafchromic films.

Some radiotherapy patients are treated with titanium surgical aneurysm clips in the radiation field. This is of particular importance for stereotactic radiosurgery brain treatments, where the length of the blade of the clip may be comparable to the size of the radiation field. This study seeks to determine the extent of the dosimetric effects caused by surgical clips in stereotactic radiosurgery, using polyacrylamide gel phantoms and EBT type Gafchromic films. Using gel phantoms scanned with magnetic resonance imaging scanner, dose enhancement of around 20% was noted at distances less than 2 mm away from the clip surface. Gafchromic films showed about 6% variations in the dose up to few millimeters from the clip. These experimental results confirmed results predicted by Monte Carlo simulation techniques for higher density material surgical clips such as lead and platinum. Moreover, these experimental measurements clearly indicate dose reduction due to radiation attenuation behind the clip of about 4%.

High-resolution measurements of small field beams using polymer gels.

Small field sizes are increasingly becoming important in radiotherapy particularly since the introduction of intensity-modulated radiation therapy (IMRT) techniques. It is normally a challenging task to reliably measure the delivered dose and to determine its distribution in a medium for such small fields using conventional-type dosimeters such as gas ionisation chambers. Recently, attempts have been made to use films, but they are not tissue equivalent, they measure the dose only in two dimensions and they are not as responsive to radiations. In the present work, polyacrylamide gel (PAG) dosimeters are employed to measure the dose and its distribution in three dimensions for very small field sizes, such as those typically used in stereotactic radiosurgery. Field sizes of 6 x 6 and 18 x 18 mm in width are investigated. The results show an agreement with radiochromic film and ionisation diode measurements, with some variation in measured doses near the edge of the field, where the gel data decreases more rapidly than the other methods.

Paleoecological assessment of watershed history in PRIMENet watersheds at Acadia National Park, USA.

Paleoecological reconstructions of forest stand histories for two upland watersheds at Acadia National Park in Maine were completed to support related watershed chemistry studies. The project hypothesis was that forest type and fire history influence long-term cycling and storage of atmospheric mercury and nitrogen within watersheds. The reconstructions document differences in major vegetation composition and disturbance between the burned and unburned watersheds during the past several centuries. Pollen and charcoal stratigraphies from organic sediment accumulations in forested wet depressions indicate that the present experimental design of contrasting disturbance and forest histories has persisted during recent centuries. The unburned watershed has been dominated by spruce (Picea rubens) and fir (Abies balsamea) for 500 years or more and has not recently burned or been substantially cleared. The burned watershed is dominated by a heterogeneous forest of patchy hardwood, mixed wood, and softwood stands. A large portion of this watershed burned severely in 1947 and probably more than once in the 1800s, and has supported heterogeneous successional forests for 200 years or longer. Overall, these results support the underlying premise that the experimental design of this watershed research can be used to infer landscape controls on biogeochemical processes.

Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study.

Cancer of unknown primary site (CUP) represents up to 5% of all cancer diagnoses and is associated with poor survival. We have performed a prospective multicentre phase 2 trial to evaluate efficacy and toxicity of the combination of gemcitabine (G) and carboplatin (C) for patients with CUP. Patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospectively designated investigation and who had ECOG performance status 0-2 were treated with G 1000 mg m(-2) intravenously (i.v.) days 1 and 8, and C AUC 5 i.v. on day 8 every 3 weeks to a maximum of nine cycles. The primary end points were response rate, and toxicity, with secondary end points of progression-free survival and overall survival. Fifty-one (23 male, 27 female) patients were enrolled (one patient ineligible), with a median age of 69 years (range 41-83 years). Fifty patients were evaluable for toxicity and 46 patients were evaluable for efficacy. The overall response rate to the GC regimen was 30.5%. With a median follow-up of 24 months, the median progression-free survival was 18 weeks (4.2 months) and the median overall survival was 34 weeks (7.8 months). The frequency of grade 3 or 4 toxicity was low. Nausea/vomiting was the most common side effect, but was usually only mild in severity. Uncomplicated neutropenia (14%), thrombocytopenia (10%) and anaemia (8%) were the most common causes of grade 3-4 toxicity. The regimen was very well tolerated, particularly in the elderly. The GC regimen is an active regimen in CUP with excellent tolerability and should be considered particularly for elderly patients with CUP.

Chronic eosinophilic leukemia presenting with autoimmune hemolytic anemia and erythrophagocytosis by eosinophils.

Eosinophils function primarily as secretory cells and phagocytosis by eosinophils is rarely seen. We describe a case of chronic eosinophilic leukemia (CEL) in a 72-year-old male with a history of previously treated non-Hodgkin's lymphoma (NHL) presenting with erythrophagocytosis by eosinophils and an associated autoimmune hemolytic anemia (AIHA). This patient did not show evidence of relapsed NHL. The patient's blood showed a markedly elevated eosinophil count of 16 x 10(9)/L [normal 0-0.45 x 10(9)/L] on a background of myelodysplasia and features of AIHA. Prominent erythrophagocytosis by eosinophils was visualized in the blood and in the bone marrow. Numerous Charcot-Leyden crystals were also seen in the bone marrow amid increased numbers of eosinophils and the presence of dysplastic granulopoiesis. AIHA is rarely described in the setting of CEL. More significantly, this represents the first case report to describe erythrophagocytosis by eosinophils.

Development of an integrated microelectrode/microelectronic device for brain implantable neuroengineering applications.

An ultra-low power analog CMOS chip and a silicon based microelectrode array have been fully integrated to a microminiaturized "neuroport" for brain implantable neuroengineering applications. The CMOS IC included preamplifier and multiplexing circuitry, and a hybrid flip-chip bonding technique was developed to fabricate a functional , encapsulated microminiaturized neuroprobe device. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, suggesting that the new neuroport can form a prime platform for the development of a microminiaturized neural interface to the brain in a single implantable unit.

Photovoltaic energy converter as a chipscale high efficiency power source for implanted active microelectronic devices.

We report the development of a microscale photovoltaic energy converter which has been designed and implemented to deliver power to CMOS-based microelectronic chips. The design targets the delivery of voltages on the order of 3V with power levels in excess of 10 mW. The geometry of the prototype device, which has been fabricated and tested, is specifically designed for coupling to an optical fiber, to facilitate remote power delivery in implantable component environment.

Field verification of Test-mate ChE.

The objective was to evaluate the ability of the Test-mate ChE to determine acetylcholinesterase (AChE) activity under field conditions. To mimic nerve agent exposure, the U.S. Army Medical Research Institute of Chemical Defense spiked blood samples with variable amounts of soman. Blinded to the identity of the samples, the 520th Theater Army Medical Laboratory tested the samples during a field training exercise inside their environmentally controlled mobile facility. The technicians repeated measurements for 6 consecutive days, and on 1 of the days repeated the measurements six times. The technicians accurately identified all of the samples and quantified the AChE activity. The major trend was that the Test-mate ChE is more precise and reproducible for smaller doses of soman. The results were reliable over all temperatures during the field exercise. In conclusion, the Test-mate ChE is a reliable field instrument to determine blood AChE activity.

Opponent and nonopponent contributions to the zebrafish electroretinogram using heterochromatic flicker photometry.

While some lower vertebrates, such as zebrafish, do not appear to possess anatomically separate pathways of processing visual information (such as M-pathways and P-pathways), it is believed that separate processing of the visual stimulus (such as luminance and chromatic processing) is a basic requirement of vertebrate vision. In this study, spectral sensitivity functions were obtained from electroretinogram responses to heterochromatic flicker photometry stimuli at several flicker rates, including a low flicker rate (2 Hz), in an attempt to predominantly stimulate chromatic processes and a high flicker rate (16 Hz), in an attempt to predominantly stimulate luminance processes. In addition, chromatic adaptation was used to isolate and examine the temporal properties of the different cone-type contributions to the electroretinogram response. Spectral sensitivity functions based on responses to heterochromatic stimuli of a low flicker rate appeared to receive both opponent and nonopponent contributions; however, when the stimulus flicker rate was high, spectral sensitivity appeared to be a function of only nonopponent mechanisms. Also, the differences in cone contributions to the spectral sensitivity functions across the different flicker rates appear to be related to the temporal properties of the cone contributions to the electroretinogram response.

Injection of highly supersaturated oxygen solutions without nucleation.

It is possible to inject highly supersaturated aqueous solutions of gas through a small capillary into an aqueous environment without the formation of significant gas bubbles. Such a technique has considerable potential therapeutic value in the treatment, for example, of heart attacks and strokes. The present paper is the second in a series (see Brereton et al. [1]) investigating the basic phenomenon behind this surprising effect. Recent experiments clearly demonstrate that the nucleation, when it does occur, results from heterogeneous nucleation on the interior surface of the distal end of the capillary. This paper describes the effects of the treatment of this interior surface on the nucleation processes and the results of high speed video observations of the phenomena. A heterogeneous nucleation model is presented which is in accord with the experimental observations.