Heavy fermions. Unconventional Fermi surface in an insulating state.

Insulators occur in more than one guise; a recent finding was a class of topological insulators, which host a conducting surface juxtaposed with an insulating bulk. Here, we report the observation of an unusual insulating state with an electrically insulating bulk that simultaneously yields bulk quantum oscillations with characteristics of an unconventional Fermi liquid. We present quantum oscillation measurements of magnetic torque in high-purity single crystals of the Kondo insulator SmB6, which reveal quantum oscillation frequencies characteristic of a large three-dimensional conduction electron Fermi surface similar to the metallic rare earth hexaborides such as PrB6 and LaB6. The quantum oscillation amplitude strongly increases at low temperatures, appearing strikingly at variance with conventional metallic behavior.

Paget-Schroetter syndrome: A review and Algorithm (WASPS-IR).

Venous compression syndromes are rare and occur due to the entrapment of vein(s) in confined anatomical spaces bounded by osseous and non-osseous structures. Here we present a review of Paget-Schroetter Syndrome, an important cause of upper extremity of deep vein thrombosis, its associated clinical and radiological findings as well as treatment options.

High-magnetic-field lattice length changes in URu2Si2.

We report high-magnetic-field (up to 45 T) c-axis thermal-expansion and magnetostriction experiments on URu(2)Si(2) single crystals. The sample length change ΔL(c)(T(HO))/L(c) associated with the transition to the "hidden order" phase becomes increasingly discontinuous as the magnetic field is raised above 25 T. The reentrant ordered phase III is clearly observed in both the thermal expansion ΔL(c)(T)/L(c) and magnetostriction ΔL(c)(B)/L(c) above 36 T, in good agreement with previous results. The sample length is also discontinuous at the boundaries of this phase, mainly at the upper boundary. A change in the sign of the coefficient of thermal expansion α(c)=1/L(c)(∂ΔL(c)/∂T) is observed at the metamagnetic transition (B(M) ~ 38 T), which is likely related to the existence of a quantum critical end point.

Successive phase transitions and extended spin-excitation continuum in the S=1/2 triangular-lattice antiferromagnet Ba3CoSb2O9.

Using magnetic, thermal, and neutron measurements on single-crystal samples, we show that Ba3CoSb2O9 is a spin-1/2 triangular-lattice antiferromagnet with the c axis as the magnetic easy axis and two magnetic phase transitions bracketing an intermediate up-up-down phase in magnetic field applied along the c axis. A pronounced extensive neutron-scattering continuum above spin-wave excitations, observed below T(N), implies that the system is in close proximity to one of two spin-liquid states that have been predicted for a 2D triangular lattice.

High resolution miniature dilatometer based on an atomic force microscope piezocantilever.

Thermal expansion, or dilation, is closely related to the specific heat, and provides useful information regarding material properties. The accurate measurement of dilation in confined spaces coupled with other limiting experimental environments such as low temperatures and rapidly changing high magnetic fields requires a new sensitive millimeter size dilatometer that has little or no temperature and field dependence. We have designed an ultracompact dilatometer using an atomic force microscope piezoresistive cantilever as the sensing element and demonstrated its versatility by studying the charge density waves in alpha uranium to high magnetic fields (up to 31 T). The performance of this piezoresistive dilatometer was comparable to that of a titanium capacitive dilatometer.

Heavy holes as a precursor to superconductivity in antiferromagnetic CeIn3.

Numerous phenomenological parallels have been drawn between f- and d-electron systems in an attempt to understand their display of unconventional superconductivity. The microscopics of how electrons evolve from participation in large moment antiferromagnetism to superconductivity in these systems, however, remains a mystery. Knowing the origin of Cooper paired electrons in momentum space is a crucial prerequisite for understanding the pairing mechanism. Of special interest are pressure-induced superconductors CeIn(3) and CeRhIn(5) in which disparate magnetic and superconducting orders apparently coexist-arising from within the same f-electron degrees of freedom. Here, we present ambient pressure quantum oscillation measurements on CeIn(3) that crucially identify the electronic structure-potentially similar to high-temperature superconductors. Heavy hole pockets of f-character are revealed in CeIn(3), undergoing an unexpected effective mass divergence well before the antiferromagnetic critical field. We thus uncover the softening of a branch of quasiparticle excitations located away from the traditional spin fluctuation-dominated antiferromagnetic quantum critical point. The observed Fermi surface of dispersive f-electrons in CeIn(3) could potentially explain the emergence of Cooper pairs from within a strong moment antiferromagnet.

A multi-component Fermi surface in the vortex state of an underdoped high-Tc superconductor.

To understand the origin of superconductivity, it is crucial to ascertain the nature and origin of the primary carriers available to participate in pairing. Recent quantum oscillation experiments on high-transition-temperature (high-T(c)) copper oxide superconductors have revealed the existence of a Fermi surface akin to that in normal metals, comprising fermionic carriers that undergo orbital quantization. The unexpectedly small size of the observed carrier pocket, however, leaves open a variety of possibilities for the existence or form of any underlying magnetic order, and its relation to d-wave superconductivity. Here we report experiments on quantum oscillations in the magnetization (the de Haas-van Alphen effect) in superconducting YBa(2)Cu(3)O(6.51) that reveal more than one carrier pocket. In particular, we find evidence for the existence of a much larger pocket of heavier mass carriers playing a thermodynamically dominant role in this hole-doped superconductor. Importantly, characteristics of the multiple pockets within this more complete Fermi surface impose constraints on the wavevector of any underlying order and the location of the carriers in momentum space. These constraints enable us to construct a possible density-wave model with spiral or related modulated magnetic order, consistent with experimental observations.

A first-in-human phase I trial of locally delivered human plasmin for hemodialysis graft occlusion.

BACKGROUND: Hemodialysis (HD) grafts often fail because of stenosis at the venous anastomosis and thrombotic occlusion. Percutaneous management relies on thrombolysis with plasminogen activators, mechanical removal of thrombus, and angioplasty of the stenotic lesion. OBJECTIVES: This report describes a phase I trial using Plasmin (Human) TAL 05-00018, a direct-acting fibrinolytic agent, to evaluate safety and, secondarily, to establish effective thrombolytic dosing. PATIENTS/METHODS: Six cohorts of five patients with acute HD graft occlusion documented by angiography were treated with escalating dosages of plasmin (1, 2, 4, 8, 12, and 24 mg) infused over 30 min via criss-crossed pulse-spray catheters within the graft. The primary efficacy endpoint was > or =50% thrombolysis, as determined by comparison of pre-plasmin and 30-min post-plasmin fistulograms. RESULTS: Of 31 subjects who received study drug (safety population), one withdrew and 30 completed the trial (evaluable for efficacy). There was no significant change in plasma alpha-2 antiplasmin or fibrinogen concentration, major bleeding did not occur, and there were no deaths. Serious adverse events in four patients were not related to the study drug. There was a dose-response relationship for the primary efficacy endpoint, all five subjects receiving 24 mg achieving >75% lysis. CONCLUSIONS: This first phase I study of Plasmin (Human) TAL 05-00018, infused into thrombosed HD grafts, documents safety at dosages of 1-24 mg and an effective thrombolytic dosage of 24 mg. The results establish a foundation for further clinical study of catheter-based plasmin administration in thrombotic disorders.

Magnetic-field-induced lattice anomaly inside the superconducting state of CeCoIn5: anisotropic evidence of the possible Fulde-Ferrell-Larkin-Ovchinnikov state.

We report high magnetic field linear magnetostriction experiments on CeCoIn5 single crystals. Two features are remarkable: (i) a sharp discontinuity in all the crystallographic axes associated with the upper superconducting critical field B(c2) that becomes less pronounced as the temperature increases and (ii) a distinctive second orderlike feature observed only along the c axis in the high field (10 T < or approximately B< or = B(c2)) low temperature (T < or approximately 0.35 K) region. This second order transition is observed only when the magnetic field lies within 20 degrees of the ab planes and there is no signature of it above B(c2), which raises questions regarding its interpretation as a field induced magnetically ordered phase. Good agreement with previous results suggests that this anomaly is related to the transition to a possible Fulde-Ferrel-Larkin-Ovchinnikov superconducting state.

Magnetic enhancement of superconductivity from electron spin domains.

Since the discovery of superconductivity, there has been a drive to understand the mechanisms by which it occurs. The BCS (Bardeen-Cooper-Schrieffer) model successfully treats the electrons in conventional superconductors as pairs coupled by phonons (vibrational modes of oscillation) moving through the material, but there is as yet no accepted model for high-transition-temperature, organic or 'heavy fermion' superconductivity. Experiments that reveal unusual properties of those superconductors could therefore point the way to a deeper understanding of the underlying physics. In particular, the response of a material to a magnetic field can be revealing, because this usually reduces or quenches superconductivity. Here we report measurements of the heat capacity and magnetization that show that, for particular orientations of an external magnetic field, superconductivity in the heavy-fermion material CeCoIn(5) is enhanced through the magnetic moments (spins) of individual electrons. This enhancement occurs by fundamentally altering how the superconducting state forms, resulting in regions of superconductivity alternating with walls of spin-polarized unpaired electrons; this configuration lowers the free energy and allows superconductivity to remain stable. The large magnetic susceptibility of this material leads to an unusually strong coupling of the field to the electron spins, which dominates over the coupling to the electron orbits.

Delta9-tetrahydrocannabivarin as a marker for the ingestion of marijuana versus Marinol: results of a clinical study.

Delta9-tetrahydrocannabinol (THC), the main psychologically active ingredient of the cannabis plant (marijuana), has been prepared synthetically and used as the bulk active ingredient of Marinol, which was approved by the FDA for the control of nausea and vomiting in cancer patients receiving chemotherapy and as an appetite stimulant for AIDS patients. Because the natural and the synthetic THC are identical in all respects, it is impossible to determine the source of the urinary metabolite of THC, 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), in a urine specimen provided in a drug-testing program. Over the last few years there has been a need to determine whether a marijuana positive drug test is the result of the ingestion of marijuana (or a related product) or whether it results from the sole use of Marinol. We have previously proposed the use of delta9-tetrahydrocannabivarin (THCV, the C3 homologue of THC) as a marker for the ingestion of marijuana (or a related product) because THCV is a natural component of most cannabis products along with THC and does not exist in Marinol. We have also reported that THCV is metabolized by human hepatocytes to 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (THCV-COOH); therefore, the presence of the latter in a urine specimen would indicate that the donor must have used marijuana or a related product (with or without Marinol). In this study, we provide clinical data showing that THCV-COOH is detected in urine specimens collected from human subjects only after the ingestion of marijuana and not after the ingestion of Marinol (whether the latter is ingested orally or by smoking). Four subjects (male and female) participated in the study in a three-session, within-subject, crossover design. The sessions were conducted at one-week intervals. Each subject received, in separate sessions and in randomized order, an oral dose of Marinol (15 mg), a smoked dose of THC (16.88 mg) in a placebo marijuana cigarette, or a smoked dose of marijuana (2.11% THC and 0.12% THCV). Urine samples were collected and vital signs were monitored every 2 h for a 6-h period following drug administration. Subjects were then transported home, were given sample collection containers and logbooks, and were instructed to record at home the volume and time of every urine collection for 24 h, and once a day for the remainder of a week (6 days). Subjects were also instructed to freeze the urine samples until the next session. All urine samples were analyzed by GC-MS for THC-COOH and THCV-COOH using solid-phase extraction and derivatization procedure on RapidTrace and TBDMS as the derivative. The method had a limit of detection of 1.0 ng/mL and 1.0 ng/mL for THCV-COOH and THC-COOH, respectively.

Identification and quantitation of 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid, a major metabolite of delta9-tetrahydrocannabivarin.

After incubation of delta9-tetrahydrocannabivarin with human hepatocytes, a major metabolic product was detected by gas chromatography-mass spectrometry that showed identical retention time and mass spectrum to the synthetic 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (11-nor-delta9-THCV-9-COOH). Analysis of human urine specimens from marijuana users and plasma samples from Marinol users showed that 11-nor-delta9-THCV-9-COOH was only present in urine specimens of marijuana users. These results supported the conclusion that identification of 11-nor-delta9-THCV-9-COOH in a donor's urine specimen indicates the use or ingestion of cannabis-related product(s) and would not explain the sole use of Marinol.

Profiles of urine samples taken from Ecstasy users at Rave parties: analysis by immunoassays, HPLC, and GC-MS.

The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is increasing throughout the world. They have become popular drugs, especially at all-night techno dance parties (Raves), and their detection is becoming an important issue. Presently, there are no MDMA- or MDA-specific immunoassays on the market, and detection of the designer amphetamines is dependent upon the use of commercially available amphetamine assays. The success of this approach has been difficult to assess because of the general unavailability of significant numbers of samples from known drug users. The objectives of the present study are to characterize the drug content of urine samples from admitted Ecstasy users by chromatographic methods and to assess the ability of the available amphetamine/methamphetamine immunoassays to detect methylenedioxyamphetamines. We found that, when analyzed by high-performance liquid chromatography with diode-array detection (HPLC-DAD), 64% of 70 urine samples (by gas chromatography-mass spectrometry [GC-MS]: 88% of 64 urine samples) obtained from Rave attendees contained MDMA and/or 3,4-methylenedioxyamphetamine (MDA) alone or in combination with amphetamine, methamphetamine, or other designer amphetamines such as 3,4-methylenedioxyethylamphetamine (MDEA). This suggests that the majority of the Ravers are multidrug users. At the manufacturer's suggested cutoffs, the Abbott TDx Amphetamine/Methamphetamine II and the new Roche HS Amphetamine/MDMA assays demonstrated greater detection sensitivity for MDMA than the other amphetamine immunoassays tested (Abuscreen OnLine Hitachi AMPS, Abuscreen OnLine Integra AMPS, Abuscreen OnLine Integra AMPSX, CEDIA AMPS, and EMIT II AMPS). There is 100% agreement between each of the two immunoassays with the reference chromatographic methods, HPLC-DAD and GC-MS, for the detection of methylenedioxyamphetamines.

Pullout properties of 3.5-mm AO/ASIF self-tapping and cortex screws in a uniform synthetic material and in canine bone.

OBJECTIVES--To compare the pullout properties of 3.5-mm AO/ASIF self-tapping screws (STS) to corresponding standard cortex screws (CS) in a uniform synthetic test material and in canine femoral bone. The influence of screw-insertion technique, test material, and test-material thickness were also assessed. STUDY DESIGN--In vitro experimental study. SAMPLE POPULATION--Two independent studies: a uniform synthetic test material and paired femurs from mature dogs. METHODS-Mechanical testing was performed in accordance with standards established by the American Society for Testing and Materials for determination of axial pullout strength of medical bone screws. Completely inserted STS, completely inserted CS, and incompletely inserted STS were tested in 3 groups of 10 test specimens each in 4.96-mm and 6.8-mm thick sheets of synthetic material. In the bone study, group 1 consisted of 24 completely inserted STS compared with 24 completely inserted CS, and group 2 consisted of 24 incompletely inserted STS versus 24 completely inserted CS. Comparisons were made between paired femurs at corresponding insertion sites. Pullout data were normalized, thereby eliminating the effect of test-material thickness on pullout properties. Mean values were compared using 2-way ANOVA. Statistical significance was set at P <.05. RESULTS--In both the 4.96-mm and 6.8-mm synthetic material, pullout testing of the completely inserted STS demonstrated significantly greater yield strength and ultimate strength than completely inserted CS. There was no significant difference between incompletely inserted STS and completely inserted STS. The 6.8-mm test material significantly increased yield strength and ultimate strength for all test groups compared with the 4.96-mm test material. In canine bone, there was no significant difference in yield strength of completely inserted STS and completely inserted CS. Yield strength of completely inserted STS and completely inserted CS were significantly greater than incompletely inserted STS. CONCLUSIONS--Pullout properties of completely inserted STS were significantly greater than corresponding CS in a uniform test material. In canine bone, the pullout strength of STS and CS were not different. Incomplete STS insertion resulted in an 18% reduction in holding power as compared with completely inserted CS and STS in canine bone. CLINICAL RELEVANCE--The length of STS used in canine bone should be such that the cutting flutes extend beyond the trans cortex to maximize pullout strength.

GC-MS determination of heroin metabolites in meconium: evaluation of four solid-phase extraction cartridges.

A procedure for extraction of heroin and metabolites for gas chromatography-mass spectrometry (GC-MS) analysis of meconium specimens that would allow detection of these analytes at low levels was needed. Solid-phase extraction (SPE) cartridges were therefore evaluated for their effectiveness in sample preparation. Four different types of commercially available extraction cartridges were used. Heroin, 6-monoacetylmorphine (6-MAM), morphine, and codeine were extracted from meconium samples using these SPE cartridges and then simultaneously analyzed using GC-MS. In each case, the extraction efficiency, linearity range, limit of detection (LOD), limit of quantitation (LOQ), between-run precision, and within-run precision were determined. Although satisfactory results were obtained with the four different types of SPE cartridges, best overall performance was observed using Clean Screen columns following the procedures outlined here. LODs as low as 20 ng/g for codeine, 10 ng/g for morphine, and 2.5 ng/g for 6-MAM were obtained, and LOQs as low as 20 ng/g for codeine, 10 ng/g for morphine, and 5 ng/g for 6-MAM were obtained. In all cases linearities were observed (r = > 0.99) for codeine, morphine, and 6-MAM over a wide concentration range (100-2000, 100-2000, and 5-100, respectively). At 50 ng/g codeine and morphine and 10 ng/g 6-MAM, the precision of analysis using these cartridges showed coefficients of variation ranging from 4.75% to 15.5%.

Analysis of methadone and its metabolites in meconium by enzyme immunoassay (EMIT) and GC-MS.

An EMIT-ETS d.a.u. immunoassay screening method for methadone in meconium and a gas chromatography-mass spectrometry (GC-MS) method for methadone and its metabolites including 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP) in meconium were described. The GC-MS method showed good linearity (r2 > or = 0.998) over a concentration range of 25-2000 ng/g with limits of detection of 10, 25, and 10 ng/g for methadone, EDDP, and EMDP, respectively, and a limit of quantitation of 25 ng/g for all three analytes. Fifty pooled meconium samples were screened using a cutoff of 200 ng/g, and all samples screened negative. GC-MS analysis of all samples showed four samples to contain methadone (35.2 to 79.9 ng/g), EDDP (28.5 to 557.2 ng/g), or both, with no detectable amount of EMDP. The negative results on the four specimens at the cutoff used may be explained by the fact that EMIT-ETS d.a.u. antibody for methadone was specific to the parent drug. The results point to the fact that immunoassays should be directed to EDDP for detection of prenatal exposure of methadone through analysis of meconium specimens.

Sparse matrix approximation method for an active optical control system.

We develop a sparse matrix approximation method to decompose a wave front into a basis set of actuator influence functions for an active optical system consisting of a deformable mirror and a segmented primary mirror. The wave front used is constructed by Zernike polynomials to simulate the output of a phase-retrieval algorithm. Results of a Monte Carlo simulation of the optical control loop are compared with the standard, nonsparse approach in terms of accuracy and precision, as well as computational speed and memory. The sparse matrix approximation method can yield more than a 50-fold increase in the speed and a 20-fold reduction in matrix size and a commensurate decrease in required memory, with less than 10% degradation in solution accuracy. Our method is also shown to be better than when elements are selected for the sparse matrix on a magnitude basis alone. We show that the method developed is a viable alternative to use of the full control matrix in a phase-retrieval-based active optical control system.

Investigation of nitrite adulteration on the immunoassay and GC-MS analysis of cannabinoids in urine specimens.

Nitrite ion has been identified as the active ingredient of two commercial adulterants that could cause discrepant results between the immunoassay screening and gas chromatographic-mass spectrometric (GC-MS) confirmation of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in urine. Procedures to chemically convert the nitrite ion at the beginning of sample preparation for GC-MS analysis may not overcome all nitrite adulteration cases because portions of the THCCOOH might have been lost between the time of sample collection and the time of analysis. This study was conducted to further investigate the influence of both urine sample matrix and the duration of nitrite exposure on nitrite interference of THCCOOH detection. Forty clinical "THC-positive samples" that had been screened and confirmed positive for the presence of THCCOOH were spiked with 0.15M or 0.3M of nitrite. The levels of THCCOOH at various time intervals after nitrite spiking were monitored by instrument-based cannabinoids immunoassays (Syva EMIT d.a.u. and/or Roche Abuscreen ONLINE assays) and by an onsite THC immunoassay (Roche ONTRAK TESTSTIK). Results from this report demonstrate that the two outstanding "urine specimen factors" that dictated the effectiveness of the nitrite adulteration were urinary pH and the original drug concentration before nitrite spiking. Significant decreases in the immunoassay results could be observed within 4 h of nitrite treatment in the majority of samples with acidic urinary pH values. Regardless of their original concentration of THCCOOH (GC-MS ranging from 33 to 488 ng/mL), all of the 20 samples that had acidic pH values gave negative immunoassay results 1 day after nitrite adulteration. In contrast, the immunoassay results of samples with neutral or basic pH values were less affected by nitrite exposure in the same studies. Approximately two-thirds of the samples with pH values greater than 7.0 remained immunoassay-positive 3 days after nitrite spiking. Nevertheless, some of the adulterated urine that showed no change in immunoassay results might exhibit significant decrease in GC-MS recoveries even with bisulfite treatment, collaborating with the observations that a portion of samples screened positive with THC immunoassay in the laboratory could fail to confirm with GC-MS analysis. The decrease or loss of immunoassay detectable cannabinoid cross-reactives in acidic "THC-positive samples" can be attenuated by chemically increasing the pH value of the samples to the basic pH range.

GC-MS analysis of the total delta9-THC content of both drug- and fiber-type cannabis seeds.

A GC-MS method was performed to determine the total delta9-THC content in both drug- and fiber-type cannabis seeds. Drug-type seeds were found to contain much higher levels of delta9-THC (35.6-124 microg/g) than fiber (hemp) seeds (0-12 microg/g). The majority of delta9-THC was found to be located on the surface of the seeds. Approximately 90% of the total delta9-THC was removed by a simple, quick wash with chloroform. Washed drug-type seeds contained less than 10 microg/g. Separation of the seeds into the kernel and testa showed that the bulk of delta9-THC is located in the testa, mainly on the outside. The kernels of drug- and fiber-type cannabis seeds contained less than 2 and 0.5 microg delta9-THC/g seeds, respectively. Fluctuations in the delta9-THC content of different replicates of the same type of seeds could be the result of the degree of contamination on the outside of the seeds.