Imaging spontaneous currents in superconducting arrays of pi-junctions

Superconductors separated by a thin tunneling barrier exhibit the Josephson effect that allows charge transport at zero voltage, typically with no phase shift between the superconductors in the lowest energy state. Recently, Josephson junctions with ground state phase shifts of pi proposed by theory three decades ago have been demonstrated. In superconducting loops, pi-junctions cause spontaneous circulation of persistent currents in zero magnetic field, analogous to spin-1/2 systems. Here we image the spontaneous zero-field currents in superconducting networks of temperature-controlled pi-junctions with weakly ferromagnetic barriers using a scanning SQUID microscope. We find an onset of spontaneous supercurrents at the 0-pi transition temperature of the junctions Tpi = 3 K. We image the currents in non-uniformly frustrated arrays consisting of cells with even and odd numbers of pi-junctions. Such arrays are attractive model systems for studying the exotic phases of the 2D XY-model and achieving scalable adiabatic quantum computers.Comment: Pre-referee version. Accepted to Nature Physic

Revealing the electronic structure of a carbon nanotube carrying a supercurrent

Carbon nanotubes (CNTs) are not intrinsically superconducting but they can carry a supercurrent when connected to superconducting electrodes. This supercurrent is mainly transmitted by discrete entangled electron-hole states confined to the nanotube, called Andreev Bound States (ABS). These states are a key concept in mesoscopic superconductivity as they provide a universal description of Josephson-like effects in quantum-coherent nanostructures (e.g. molecules, nanowires, magnetic or normal metallic layers) connected to superconducting leads. We report here the first tunneling spectroscopy of individually resolved ABS, in a nanotube-superconductor device. Analyzing the evolution of the ABS spectrum with a gate voltage, we show that the ABS arise from the discrete electronic levels of the molecule and that they reveal detailed information about the energies of these levels, their relative spin orientation and the coupling to the leads. Such measurements hence constitute a powerful new spectroscopic technique capable of elucidating the electronic structure of CNT-based devices, including those with well-coupled leads. This is relevant for conventional applications (e.g. superconducting or normal transistors, SQUIDs) and quantum information processing (e.g. entangled electron pairs generation, ABS-based qubits). Finally, our device is a new type of dc-measurable SQUID

Designing the ideal model for assessment of wound contamination after gunshot injuries: a comparative experimental study

<p>Abstract</p> <p>Background</p> <p>Modern high-velocity projectiles produce temporary cavities and can thus cause extensive tissue destruction along the bullet path. It is still unclear whether gelatin blocks, which are used as a well-accepted tissue simulant, allow the effects of projectiles to be adequately investigated and how these effects are influenced by caliber size.</p> <p>Method</p> <p>Barium titanate particles were distributed throughout a test chamber for an assessment of wound contamination. We fired .22-caliber Magnum bullets first into gelatin blocks and then into porcine hind limbs placed behind the chamber. Two other types of bullets (.222-caliber bullets and 6.5 × 57 mm cartridges) were then shot into porcine hind limbs. Permanent and temporary wound cavities as well as the spatial distribution of barium titanate particles in relation to the bullet path were evaluated radiologically.</p> <p>Results</p> <p>A comparison of the gelatin blocks and hind limbs showed significant differences (<it>p </it>< 0.05) in the mean results for all parameters. There were significant differences between the bullets of different calibers in the depth to which barium titanate particles penetrated the porcine hind limbs. Almost no particles, however, were found at a penetration depth of 10 cm or more. By contrast, gas cavities were detected along the entire bullet path.</p> <p>Conclusion</p> <p>Gelatin is only of limited value for evaluating the path of high-velocity projectiles and the contamination of wounds by exogenous particles. There is a direct relationship between the presence of gas cavities in the tissue along the bullet path and caliber size. These cavities, however, are only mildly contaminated by exogenous particles.</p

The Cosmic Infrared Background: Measurements and Implications

The cosmic infrared background records much of the radiant energy released by processes of structure formation that have occurred since the decoupling of matter and radiation following the Big Bang. In the past few years, data from the Cosmic Background Explorer mission provided the first measurements of this background, with additional constraints coming from studies of the attenuation of TeV gamma-rays. At the same time there has been rapid progress in resolving a significant fraction of this background with the deep galaxy counts at infrared wavelengths from the Infrared Space Observatory instruments and at submillimeter wavelengths from the Submillimeter Common User Bolometer Array instrument. This article reviews the measurements of the infrared background and sources contributing to it, and discusses the implications for past and present cosmic processes.Comment: 61 pages, incl. 9 figures, to be published in Annual Reviews of Astronomy and Astrophysics, 2001, Vol. 3

Longitudinal assessment of multiple sclerosis with the brain-age paradigm

OBJECTIVE: During the natural course of MS, the brain is exposed to ageing as well as disease effects. Brain ageing can be modelled statistically; the so-called 'brain-age' paradigm. Here, we evaluated whether brain-predicted age difference (brain-PAD) was sensitive to the presence of MS, clinical progression and future outcomes. METHODS: In a longitudinal, multi-centre sample of 3,565 MRI scans, in 1,204 MS and clinically-isolated syndrome (CIS) patients and 150 healthy controls (mean follow-up time: patients 3.41 years, healthy controls 1.97 years), we measured 'brain-predicted age' using T1-weighted MRI. We compared brain-PAD between MS and CIS patients and healthy controls, and between disease subtypes. Relationships between brain-PAD and Expanded Disability Status Scale (EDSS) were explored. RESULTS: MS patients had markedly higher brain-PAD than healthy controls (mean brain-PAD +10.3 years [95% CI 8.5, 12.1] versus 4.3 years [-2.1, 6.4], p < 0.001). The highest brain-PADs were in secondary-progressive MS (+19.4 years [17.1, 21.9]). Brain-PAD at study entry predicted time-to-disability progression (hazard ratio 1.02 [1.01, 1.03], p < 0.001); though normalised brain volume was a stronger predictor. Greater annualised brain-PAD increases were associated with greater annualised EDSS score (r = 0.26, p < 0.001). INTERPRETATION: The brain-age paradigm is sensitive to MS-related atrophy and clinical progression. A higher brain-PAD at baseline was associated with more rapid disability progression and the rate of change in brain-PAD related to worsening disability. Potentially, 'brain-age' could be used as a prognostic biomarker in early-stage MS, to track disease progression or stratify patients for clinical trial enrolment. This article is protected by copyright. All rights reserved

Riluzole-Rasagiline Hybrids: Toward the Development of Multi-Target-Directed Ligands for Amyotrophic Lateral Sclerosis

Polypharmacology is a new trend in amyotrophic lateral sclerosis (ALS) therapy and an effective way of addressing a multifactorial etiology involving excitotoxicity, mitochondrial dysfunction, oxidative stress, and microglial activation. Inspired by a reported clinical trial, we converted a riluzole (1)-rasagiline (2) combination into single-molecule multi-target-directed ligands. By a ligand-based approach, the highly structurally integrated hybrids 3-8 were designed and synthesized. Through a target- and phenotypic-based screening pipeline, we identified hit compound 6. It showed monoamine oxidase A (MAO-A) inhibitory activity (IC50 = 6.9 mu M) rationalized by in silico studies as well as in vitro brain permeability. By using neuronal and non-neuronal cell models, including ALS-patient-derived cells, we disclosed for 6 a neuroprotective/neuroinflammatory profile similar to that of the parent compounds and their combination. Furthermore, the unexpected MAO inhibitory activity of 1 (IC50 = 8.7 mu M) might add a piece to the puzzle of its anti-ALS molecular profile

Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874]

BACKGROUND: High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. METHODS: Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m(2)/d intravenously (IV) 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m(2)/d IV 5 days/week × 4 weeks followed by 10 MU/m(2 )subcutaneously (SC) three times per week × 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. RESULTS: The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m(2)/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m(2)/week) (p = 0.003). CONCLUSION: Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited

Cost-effectiveness of pregabalin versus venlafaxine in the treatment of generalized anxiety disorder: findings from a Spanish perspective

The objective of the present study was to describe a new model of the cost-effectiveness of treatment of generalized anxiety disorder (GAD) and its application to a comparison of pregabalin versus venlafaxine extended-release (XR) from a Spanish healthcare perspective. Microsimulation techniques, including Hamilton Anxiety Scale (HAM-A) score, number of weeks with minimal or no anxiety (HAM-A ≤ 9), and quality-adjusted life-years (QALYs), were used to predict treatment outcomes for patients with moderate-to-severe GAD who would be treated with pregabalin vs venlafaxine XR. Expected levels of healthcare utilization and unit cost of care are derived from Spanish published sources. We express cost-effectiveness alternatively in terms of incremental cost per additional week with minimal or no anxiety, and incremental cost per QALY gained [in 2007 Euros (€)]. Considering costs of drug treatment only, the incremental cost [mean (95% confidence interval)] of pregabalin (vs venlafaxine XR) would be €96 (€86, €107) per additional week with minimal or no anxiety, and €32,832 (€29,656, €36,308) per QALY gained. When other medical care costs are considered, cost-effectiveness ratios decline to €70 (€61, €80) per additional week with no or minimal anxiety, and €23,909 (€20,820, €27,006) per QALY gained. We conclude that, using a new microsimulation model of the treatment of GAD, pregabalin appears to be cost-effective vs venlafaxine XR in a Spanish healthcare setting

Grey matter volume alterations in CADASIL: a voxel-based morphometry study

CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of-interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR-corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized