Electronuclear Transition into a Spatially Modulated Magnetic State in YbRh_{2}Si_{2}.

The nature of the antiferromagnetic order in the heavy fermion metal YbRh_{2}Si_{2}, its quantum criticality, and superconductivity, which appears at low mK temperatures, remain open questions. We report measurements of the heat capacity over the wide temperature range 180 µK-80 mK, using current sensing noise thermometry. In zero magnetic field we observe a remarkably sharp heat capacity anomaly at 1.5 mK, which we identify as an electronuclear transition into a state with spatially modulated electronic magnetic order of maximum amplitude 0.1 µ_{B}. We also report results of measurements in magnetic fields in the range 0 to 70 mT, applied perpendicular to the c axis, which show eventual suppression of this order. These results demonstrate a coexistence of a large moment antiferromagnet with putative superconductivity.

Demonstration of electron acceleration in a laser-driven dielectric microstructure.

The enormous size and cost of current state-of-the-art accelerators based on conventional radio-frequency technology has spawned great interest in the development of new acceleration concepts that are more compact and economical. Micro-fabricated dielectric laser accelerators (DLAs) are an attractive approach, because such dielectric microstructures can support accelerating fields one to two orders of magnitude higher than can radio-frequency cavity-based accelerators. DLAs use commercial lasers as a power source, which are smaller and less expensive than the radio-frequency klystrons that power today's accelerators. In addition, DLAs are fabricated via low-cost, lithographic techniques that can be used for mass production. However, despite several DLA structures having been proposed recently, no successful demonstration of acceleration in these structures has so far been shown. Here we report high-gradient (beyond 250 MeV m(-1)) acceleration of electrons in a DLA. Relativistic (60-MeV) electrons are energy-modulated over 563 ± 104 optical periods of a fused silica grating structure, powered by a 800-nm-wavelength mode-locked Ti:sapphire laser. The observed results are in agreement with analytical models and electrodynamic simulations. By comparison, conventional modern linear accelerators operate at gradients of 10-30 MeV m(-1), and the first linear radio-frequency cavity accelerator was ten radio-frequency periods (one metre) long with a gradient of approximately 1.6 MeV m(-1) (ref. 5). Our results set the stage for the development of future multi-staged DLA devices composed of integrated on-chip systems. This would enable compact table-top accelerators on the MeV-GeV (10(6)-10(9) eV) scale for security scanners and medical therapy, university-scale X-ray light sources for biological and materials research, and portable medical imaging devices, and would substantially reduce the size and cost of a future collider on the multi-TeV (10(12) eV) scale.

Two-dimensional ferromagnetism of a 3He film: influence of weak frustration.

(3)He films adsorbed on the atomically flat surface of graphite provide a model system for the study of two-dimensional magnetism on a triangular lattice. We have made a study of the regime in which the T=0 ground state of the second (3)He layer is a fully polarized ferromagnet. NMR, using broadband SQUID detection, at a range of low fields above the spin-flop transition, and over a wide temperature range 0.3-200 mK, has enabled us to disentangle the influence of sample finite size effects and magnetic field on the spin-wave spectrum. We demonstrate that the spin-wave spectrum is governed by a different effective exchange constant than that determining the high temperature magnetism. This is understood in terms of frustrated atomic ring exchange.

NMR signature of one-dimensional behavior of 3He in nanopores.

We have performed thermodynamic and NMR relaxation time measurements of 3He adsorbed in the pores of the mesoporous molecular sieve MCM-41 at temperatures down to 1.7 K and at a range of frequencies up to 240 kHz. The MCM-41 substrate comprises a uniform array of quasi-1D straight pores with a diameter of 2.3 nm. We preplated the pores with a monolayer of 4He to achieve an effective diameter of 1.6 nm at low temperatures. We made NMR measurements as a function of line density and frequency to investigate the spin dynamics and the effect of dimensionality. We observed T(1) is proportional to ω1/2, which is characteristic of one-dimensional diffusion. At these temperatures this arises from a classical size effect in the narrow pores. Our results demonstrate the possibility to study the spin dynamics of a 1D Tomonaga-Luttinger liquid at lower temperatures, where the 3He liquid will constitute a quantum 1D system.

Risk factors for inguinal hernia repair among US adults.

PURPOSE: To investigate demographic, clinical, and behavioral risk factors for undergoing inguinal hernia repair within a large and ethnically diverse cohort. METHODS: We conducted a retrospective case-control study from 2007 to 2020 on 302,532 US individuals from a large, integrated healthcare delivery system with electronic health records, who participated in a survey of determinants of health. Participants without diagnosis or procedure record of an inguinal hernia at enrollment were included. We then assessed whether demographic (age, sex, race/ethnicity), clinical, and behavioral factors (obesity status, alcohol use, cigarette smoking and physical activity) were predictors of undergoing inguinal hernia repair using survival analyses. Risk factors showing statistical significance (P < 0.05) in the univariate models were added to a multivariate model. RESULTS: We identified 7314 patients who underwent inguinal hernia repair over the study period, with a higher incidence in men (6.31%) compared to women (0.53%). In a multivariate model, a higher incidence of inguinal hernia repair was associated with non-Hispanic white race/ethnicity, older age, male sex (aHR = 13.55 [95% confidence interval 12.70-14.50]), and more vigorous physical activity (aHR = 1.24 [0.045]), and alcohol drinker status (aHR = 1.05 [1.00-1.11]); while African-American (aHR = 0.69 [0.59-0.79]), Hispanic/Latino (aHR = 0.84 [0.75-0.91]), and Asian (aHR = 0.35 [0.31-0.39]) race/ethnicity, obesity (aHR = 0.33 [0.31-0.36]) and overweight (aHR = 0.71 [0.67-0.75]) were associated with a lower incidence. The use of cigarette was significantly associated with a higher incidence of inguinal hernia repair in women (aHR 1.23 [1.09-1.40]), but not in men (aHR 0.96 [0.91-1.02]). CONCLUSION: Inguinal hernia repair is positively associated with non-Hispanic white race/ethnicity, older age, male sex, increased physical activity, alcohol consumption and tobacco use (only in women); while negatively associated with obesity and overweight status. Findings from this large and ethnically diverse study may support future prediction tools to identify patients at high risk of this surgery.

Quantum transport in mesoscopic 3He films: experimental study of the interference of bulk and boundary scattering.

We discuss the mass transport of a degenerate Fermi liquid ^{3}He film over a rough surface, and the film momentum relaxation time, in the framework of theoretical predictions. In the mesoscopic regime, the anomalous temperature dependence of the relaxation time is explained in terms of the interference between elastic boundary scattering and inelastic quasiparticle-quasiparticle scattering within the film. We exploit a quasiclassical treatment of quantum size effects in the film in which the surface roughness, whose power spectrum is experimentally determined, is mapped into an effective disorder potential within a film of uniform thickness. Confirmation is provided by the introduction of elastic scattering centers within the film. The improved understanding of surface roughness scattering may impact on enhancing the conductivity in thin metallic films.

CXCR3 ligands promote expression of functional indoleamine 2,3-dioxygenase in basal cell carcinoma keratinocytes.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in humans worldwide. Studies suggest that BCCs exhibit immunoprotection, similar to other keratinocyte carcinomas, although the mechanisms of defence have not been defined. OBJECTIVES: To examine if indoleamine 2,3-dioxygenase (IDO), an immune privilege-associated enzyme, would be expressed in BCC, regulated in part by CXCR3. METHODS: We analysed the expression and function of IDO in human BCC (hBCC) tissues using nonlesional skin epithelial (NL) tissues as a control. RESULTS: Quantitative real-time reverse transcription-polymerase chain reaction (qPCR) revealed significant upregulation of IDO1 and IDO2 (12·5- and 19·14-fold change, respectively) in nodular hBCCs as compared with NL tissues. Immunohistochemistry showed that IDO colocalized with keratin 17, a BCC keratinocyte marker, in hBCC tissues. Western blot identified a full-length IDO (42 kDa) product and a splice variant (∼30 kDa) in BCC tissues. Kynurenine assays and qPCR were conducted to determine IDO enzymatic activity in hBCCs in vitro with CXCL11 supplementation, which has previously been shown to be required for the tumour cell growth. Addition of CXCL11 upregulated IDO2 and increased l-kynurenine concentration in a dose-dependent manner in hBCCs while normal primary keratinocytes exhibited no response. CONCLUSIONS: The expression of IDO at both mRNA and protein levels in hBCC tissues, the upregulation of IDO2 and the IDO-mediated l-kynurenine production in hBCCs with CXCL11 treatment suggest that functional IDO is synthesized by hBCC tumours and may be used as a method of immunoprotection during tumorigenesis. Also, IDO enzymatic activity may be modulated by CXCR3/CXCL11 signalling in BCCs.

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study.

AIMS/HYPOTHESIS: Cu(II)-selective chelation with trientine ameliorates cardiovascular and renal disease in a model of diabetes in rats. Here, we tested the hypothesis that Cu(II)-selective chelation might improve left ventricular hypertrophy (LVH) in type 2 diabetic patients. METHODS: We performed a 12 month randomised placebo-controlled study of the effects of treatment with the Cu(II)-selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given orally twice daily) on LVH in diabetic patients (n = 15/group at baseline) in an outpatient setting wherein participants, caregivers and those assessing outcomes were blinded to group assignment. Using MRI, we measured left ventricular variables at baseline, and at months 6 and 12. The change from baseline in left ventricular mass indexed to body surface area (LVM(bsa)) was the primary endpoint variable. RESULTS: Diabetic patients had LVH with preserved ejection fraction at baseline. Trientine treatment decreased LVM(bsa) by 5.0 +/- 7.2 g/m(2) (mean +/- SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants were analysed; p = 0.0056 compared with placebo) and by 10.6 +/- 7.6 g/m(2) at month 12 (when nine trientine-treated and 13 placebo-treated participants were analysed; p = 0.0088), whereas LVM(bsa) was unchanged by placebo treatment. In a multiple-regression model that explained ~75% of variation (R (2) = 0.748, p = 0.001), cumulative urinary Cu excretion over 12 months was positively associated with trientine-evoked decreases in LVM(bsa). CONCLUSIONS/INTERPRETATION: Cu(II)-selective chelation merits further exploration as a potential pharmacotherapy for diabetic heart disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12609000053224 FUNDING: The Endocore Research Trust; Lottery Health New Zealand; the Maurice and Phyllis Paykel Trust; the Foundation of Research, Science and Technology (New Zealand); the Health Research Council of New Zealand; the Ministry of Education (New Zealand) through the Maurice Wilkins Centre for Molecular Biodiscovery; and the Protemix Corporation.

4D modelling for rapid assessment of biventricular function in congenital heart disease.

Although more patients with congenital heart disease (CHD) are now living longer due to better surgical interventions, they require regular imaging to monitor cardiac performance. There is a need for robust clinical tools which can accurately assess cardiac function of both the left and right ventricles in these patients. We have developed methods to rapidly quantify 4D (3D + time) biventricular function from standard cardiac MRI examinations. A finite element model was interactively customized to patient images using guide-point modelling. Computational efficiency and ability to model large deformations was improved by predicting cardiac motion for the left ventricle and epicardium with a polar model. In addition, large deformations through the cycle were more accurately modeled using a Cartesian deformation penalty term. The model was fitted to user-defined guide points and image feature tracking displacements throughout the cardiac cycle. We tested the methods in 60 cases comprising a variety of congenital heart diseases and showed good correlation with the gold standard manual analysis, with acceptable inter-observer error. The algorithm was considerably faster than standard analysis and shows promise as a clinical tool for patients with CHD.

Elafin, a serine elastase inhibitor, attenuates post-cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits afer heterotopic cardiac transplantation.

We have related experimentally induced post-cardiac transplant coronary arteriopathy to increased elastolytic activity, IL-1beta, fibronectin-mediated inflammatory and smooth muscle cell (SMC) migration, and SMC proliferation. Since our in vitro studies show that a serine elastase releases SMC mitogens and facilitates IL-lbeta induction of fibronectin, we hypothesized that administration in vivo of the specific serine elastase inhibitor, elafin, would decrease the post-cardiac transplant coronary arteriopathy. Cholesterol-fed rabbits underwent a heterotopic cardiac transplant without immunosuppression and received elafin (1.79 mg/kg per d continuous infusion after a 9 mg bolus, n = 6) or vehicle (n = 6). 1 wk later, hearts were harvested for morphometric, immunohistochemical, and biochemical analyses. A > 70% decrease in the total number of coronary arteries with intimal thickening in elafin-treated compared to control donor hearts (P < 0.002) was associated with reduced vascular elastolytic activity judged by fewer breaks in the internal elastic lamina (P < 0.03), less accumulation of immunoreactive fibronectin (P < 0.02), and reduced cell proliferation quantified by proliferating cell nuclear antigen (P < 0.0001). Despite myocardial lymphocytic infiltration, wet weight of elafin-treated donor hearts was reduced by 50% compared to untreated controls (P < 0.002) and associated with relative preservation of myocyte integrity, instead of extensive myocardial necrosis (P < 0.004). This protective effect correlated with decreased myocardial elastolytic activity (P < 0.0001) and inflammatory cell proliferation (P < 0.0001) and with an elafin-inhibitable elastase in lymphocytes. Serine elastase activity thus appears an important therapeutic target for post-cardiac transplant coronary arteriopathy and myocardial necrosis induced by rejection.

On the 'Supersolid' Response of the Second Layer of 4 He on Graphite.

Recent torsional oscillator measurements on the second layer of 4 He adsorbed on graphite have identified an anomalous superfluid response over a coverage range near third-layer promotion, with four distinct coverage regimes. Here, we present details of the superfluid response in the coverage regime immediately below third-layer promotion. A scaling analysis of the inferred superfluid fraction shows the characteristic temperature governing the superfluid response to decrease, approaching zero near the coverage at which simulations predict the second layer to form a conventional incommensurate solid.

An interactive tool for rapid biventricular analysis of congenital heart disease.

Cardiac malformations are the most common birth defect. Better interventions in early life have improved mortality for children with congenital heart disease, but heart failure is a significant problem in adulthood. These patients require regular imaging and analysis of biventricular (left and right ventricular) function. In this study, we describe a rapid method to analyse left and right ventricular shape and function from cardiac MRI examinations. A 4D (3D+time) finite element model template is interactively customized to the anatomy and motion of the biventricular unit. The method was validated in 17 patients and 10 ex-vivo hearts. Interactive model updates were achieved through preconditioned conjugate gradient optimization on a multithread system, and by precomputing points predicted from a coarse mesh optimization.

Small cell lung cancer cell line derived from a primary tumor with a characteristic deletion of 3p.

Chemotherapy plus surgery is feasible and potentially effective in selected patients with small cell lung cancer (SCLC) and provides a unique opportunity to study SCLC early in its biological history. The in vitro characteristics of a SCLC cell line derived from a resected lung primary tumor after treatment with 3 courses of chemotherapy is described. The original SCLC cell line UMC-SCLC-1 exhibited features of classic SCLC with typical morphology and growth characteristics, high levels of dopa decarboxylase, bombesin-like peptides, neuron-specific enolase and calcitonin, and the presence of neurosecretory granules and demonstrated the deletion of the short arm of chromosome 3. After multiple passages, UMC-SCLC-1 gradually changed its culture characteristics to a cell line, UMC-SCLC-1A, with morphological features of large cell anaplastic carcinoma, an altered growth pattern, decrease in calcitonin, and increase in radioresistance but retained the other biochemical markers of classic SCLC (bombesin and dopa decarboxylase production). Serial DNA content analyses showed that increased aneuploidy during continuous culture in vitro was associated with the morphological changes. Both UMC-SCLC-1 and UMC-SCLC-1A demonstrated the deletion of chromosome 3p, amplification and abundant expression of N-myc, and increased expression of c-raf. Chemotherapy sensitivities were stable throughout multiple passages and correlated with in vivo response. UMC-SCLC-1A represents a unique SCLC cell line with heterogeneous properties of both classic and morphological variant SCLC cell lines. In addition, the characteristic deletion of 3p, previously described in cultures derived from metastatic lesions and heavily pretreated patients, is seen in a primary lesion early in the natural history of SCLC.

Pulsatile pituitary gonadotropin secretion during maturation of the dominant follicle in monkeys: estrogen positive feedback enhances the biological activity of LH.

In the follicular phase of the menstrual cycle, pulsatile patterns of LH and FSH secretion in monkeys change during maturation of the dominant follicle. At the preovulatory surge, the most striking event is the prodigious elevations of bioassayable LH, rising up to 50-fold within 24 h. Principally, establishment of the surge is due to marked enhancement of the amplitude of LH secretory pulses. In contrast, LH and FSH measured by RIA enter, in parallel, the surge modes of secretion approximately 5 h later than bioassayable LH and rise more slowly; the B:I ratio may reach 10:1. This same disparity between bioassayable versus immunoassayable LH was induced in castrate monkeys under estrogen positive feedback stimulation. We conclude that the preovulatory estrogen surge promotes the secretion of an LH molecule(s) having enhanced biological activity.

Partial characterization of a uteroglobin-like protein in the human uterus and its temporal relationship to prostaglandin levels in this organ.

During the past decade several corticosteroid-dependent, low mol wt proteins with phospholipase-A2 (PLA2) inhibitory activity have been described. This family of proteins is collectively known as lipocortins. Blastokinin or uteroglobin (utg), a progesterone-induced protein, first discovered in the pregnant rabbit uterus, is also a potent PLA2 inhibitor, but genetically distinct from lipocortins. Although utg has been found in rabbits, its presence in humans has not been well established. Here, we present biochemical, immunological, and immunohistological evidence for the detection of a utg-like protein in the human uterus. Since inhibition of PLA2 may modulate tissue eicosanoid levels and since rabbit utg has been reported to be a potent PLA2 inhibitor, we also studied the temporal relationship between utg and tissue prostaglandin E2 and F2 alpha levels in estrogen- and progesterone-dominated endometrial tissue. We found an inverse temporal relationship between utg-like protein and eicosanoid levels in this organ. Since some eicosanoids (e.g. prostaglandins, leukotrienes, etc.) are known to be involved in smooth muscle contractility and inflammatory processes, our findings may help to understand the pathogenesis of some human disorders in which abnormal eicosanoid production occurs.

Measurement of the sodium membrane potential by NMR.

Using nuclear magnetic resonance (NMR), we have developed a method of noninvasively determining the transmembrane sodium potential in erythrocytes by measuring intracellular and extracellular sodium concentrations. The experimental values correlated well with values obtained from standard flame photometric methods.

Suppression of lymphocyte proliferation in vitro by macromolecules in the vesicle fluid and tissue extracts of hydatidiform mole.

This study examines the effects of vesicle fluid and tissue extracts from hydatidiform mole trophoblast on lymphocyte proliferation in vitro. Samples were obtained by direct aspiration of vesicles (hydatidiform mole vesicle fluid (HMF] or homogenization of molar tissues (hydatidiform mole extract (HME] following therapeutic uterine evacuation of hydatidiform mole. Dialyzed and lyophylized HMF pooled from two patients exhibited a 30% suppression (P less than 0.05) of mitogen-induced lymphocyte proliferation at a concentration of 12.5 micrograms protein/ml. Similarly, lymphocyte transformation was significantly suppressed (P less than 0.05) by HME at concentrations of 500 and 250 micrograms/ml. Molecular weight chromatography of HME resolved 4 protein fractions. Fraction 3 (35--50 kDa) and fraction 4 (less than 35 kDa) significantly suppressed mitogen-induced lymphocyte transformation while fractions 1 and 2 demonstrated no immunosuppression. Heat treatment (56 degrees C, 30 min) abolished the immunosuppressive activity of HME as well as fractions 3 and 4. These results suggest that hydatidiform mole trophoblast contains heat-labile macromolecules which suppress mitogen-mediated lymphocyte transformation. Such trophoblast-derived factors may interfere with maternal rejection of the allograft.

Expression of Clara cell 10-kD gene in the human endometrium and its relationship to ovarian menstrual cycle.

Clara cell 10-kD (cc10-kD) protein has been suggested to be the human counterpart of rabbit uteroglobin (UG). Like UG, this protein is also a potent inhibitor of phospholipase A2 (PLA2) and a substrate of transglutaminase. Although it has been established that UG gene expression in the rabbit endometrium is stimulated by progesterone, the expression of cc10-kD gene in the human endometrium is not clearly understood. The present study was undertaken to determine whether the cc10-kD gene is expressed in the human endometrium and whether its level of expression changes in relation to the ovarian menstrual cycle. Using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence, we demonstrate that the cc10-kD gene is expressed in different stages of the menstrual cycle and that the highest level of expression is reached during the luteal phase. These results suggest that like rabbit UG, cc10-kD gene expression in the human endometrium may be stimulated by progesterone. Since cc10-kD is a potent inhibitor of PLA2 activity, this protein may play an important physiological role in regulating eicosanoid levels in the human uterus.

Treatment of persistent ectopic pregnancy with methotrexate and leukovorum rescue: a case report.

The incidence of ectopic pregnancy is increasing in the Western world, and this reproductive complication has had an adverse impact on subsequent fertility. Advances in the surgical treatment of ectopic pregnancies have been designed to preserve future reproductive potential, but conservative tubal surgery may fail to completely remove the trophoblast. Described is a case of persistent ectopic pregnancy successfully treated with methotrexate.

Life-threatening neutropenia following methotrexate treatment of ectopic pregnancy: a report of two cases.

BACKGROUND: Medical treatment of ectopic pregnancy with methotrexate is an increasingly common alternative to surgical management. Initial reports of methotrexate therapy described a very low incidence of complications. We report our experience with two patients who developed profound toxicity following methotrexate treatment of ectopic pregnancy. CASE: The first patient received a single dose of methotrexate (50 mg/m2 intramuscularly) for a confirmed ectopic pregnancy. The second patient received three doses of methotrexate (1 mg/kg). Both patients developed life-threatening neutropenia and febrile morbidity requiring hospitalization and supportive care. CONCLUSION: To our knowledge, this is the first description of significant morbidity secondary to bone marrow suppression following methotrexate treatment of ectopic pregnancy. Most patients with ectopic pregnancy who are treated with methotrexate can expect resolution of their symptoms and a low risk of mild complications. However, serious complications after this therapy are possible and may occur even with the single-dose regimen.