ZOOM or Non-ZOOM? Assessing spinal cord diffusion tensor imaging protocols for multi-centre studies

The purpose of this study was to develop and evaluate two spinal cord (SC) diffusion tensor imaging (DTI) protocols, implemented at multiple sites (using scanners from two different manufacturers), one available on any clinical scanner, and one using more advanced options currently available in the research setting, and to use an automated processing method for unbiased quantification. DTI parameters are sensitive to changes in the diseased SC. However, imaging the cord can be technically challenging due to various factors including its small size, patient-related and physiological motion, and field inhomogeneities. Rapid acquisition sequences such as Echo Planar Imaging (EPI) are desirable but may suffer from image distortions. We present a multi-centre comparison of two acquisition protocols implemented on scanners from two different vendors (Siemens and Philips), one using a reduced field-of-view (rFOV) EPI sequence, and one only using options available on standard clinical scanners such as outer volume suppression (OVS). Automatic analysis was performed with the Spinal Cord Toolbox for unbiased and reproducible quantification of DTI metrics in the white matter. Images acquired using the rFOV sequence appear less distorted than those acquired using OVS alone. SC DTI parameter values obtained using both sequences at all sites were consistent with previous measurements made at 3T. For the same scanner manufacturer, DTI parameter inter-site SDs were smaller for the rFOV sequence compared to the OVS sequence. The higher inter-site reproducibility (for the same manufacturer and acquisition details, i.e. ZOOM data acquired at the two Philips sites) of rFOV compared to the OVS sequence supports the idea that making research options such as rFOV more widely available would improve accuracy of measurements obtained in multi-centre clinical trials. Future multi-centre studies should also aim to match the rFOV technique and signal-to-noise ratios in all sequences from different manufacturers/sites in order to avoid any bias in measured DTI parameters and ensure similar sensitivity to pathological changes

Inferences Drawn from a Risk Assessment Compared Directly with a Randomized Trial of a Home Drinking Water Intervention

Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a risk assessment. Comparing the group with water treatment (active) with that without water treatment (sham), the estimated annual attributable disease rate (cases per 10,000 persons per year) from the trial provided no evidence of a significantly elevated drinking water risk [attributable risk = −365 cases/year, sham minus active; 95% confidence interval (CI), −2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6, 37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5 percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important under conditions of low risk when estimates are difficult to attain from trials. In particular, this assessment pointed toward the importance of attaining site-specific treatment data and the clear need for a better understanding of viral removal by disinfection. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches

Mid-infrared optical parametric amplifier using silicon nanophotonic waveguides

All-optical signal processing is envisioned as an approach to dramatically decrease power consumption and speed up performance of next-generation optical telecommunications networks. Nonlinear optical effects, such as four-wave mixing (FWM) and parametric gain, have long been explored to realize all-optical functions in glass fibers. An alternative approach is to employ nanoscale engineering of silicon waveguides to enhance the optical nonlinearities by up to five orders of magnitude, enabling integrated chip-scale all-optical signal processing. Previously, strong two-photon absorption (TPA) of the telecom-band pump has been a fundamental and unavoidable obstacle, limiting parametric gain to values on the order of a few dB. Here we demonstrate a silicon nanophotonic optical parametric amplifier exhibiting gain as large as 25.4 dB, by operating the pump in the mid-IR near one-half the band-gap energy (E~0.55eV, lambda~2200nm), at which parasitic TPA-related absorption vanishes. This gain is high enough to compensate all insertion losses, resulting in 13 dB net off-chip amplification. Furthermore, dispersion engineering dramatically increases the gain bandwidth to more than 220 nm, all realized using an ultra-compact 4 mm silicon chip. Beyond its significant relevance to all-optical signal processing, the broadband parametric gain also facilitates the simultaneous generation of multiple on-chip mid-IR sources through cascaded FWM, covering a 500 nm spectral range. Together, these results provide a foundation for the construction of silicon-based room-temperature mid-IR light sources including tunable chip-scale parametric oscillators, optical frequency combs, and supercontinuum generators

Risk of congenital anomalies in pregnant users of statin drugs

What is already known about this subjectCholesterol is known to be essential for fetal development.Statins, which inhibit cholesterol production, have therefore been considered as potential teratogens and are contraindicated in pregnancy.Data available thus far on the risks of congenital anomalies associated with statin therapy have come from non-analytic postmarketing surveillance studies.Given the increasing use of statins in women of childbearing age, there is a need for a population-based study on the risks of congenital anomalies associated with gestational statin use.What this study addsIn this pharmacoepidemiological study, we determined the risk of congenital anomalies in women who filled prescriptions for statins during the first trimester of pregnancy, compared with women who had stopped statins before pregnancy or those who used fibrates during pregnancy.We found no evidence of an increased risk of fetal anomalies among first-trimester statin users, or any discernable pattern of congenital anomalies among live births.However, in the absence of outcome data on nonlive births, conclusions remain uncertain

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

Apathy, but Not Depression, Reflects Inefficient Cognitive Strategies in Parkinson's Disease

The relationship between apathy, depression and cognitive impairment in Parkinson's disease (PD) is still controversial. The objective of this study is to investigate whether apathy and depression are associated with inefficient cognitive strategies in PD.In this prospective clinical cohort study conducted in a university-based clinical and research movement disorders center we studied 48 PD patients. Based on clinical evaluation, they were classified in two groups: PD with apathy (PD-A group, n = 23) and PD without apathy (PD-NA group, n = 25). Patients received clinical and neuropsychological evaluations. The clinical evaluation included: Apathy Evaluation Scale-patient version, Hamilton Depression Rating Scale-17 items, the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr staging system; the neuropsychological evaluation explored speed information processing, attention, working memory, executive function, learning abilities and memory, which included several measures of recall (immediate free, short delay free, long delay free and cued, and total recall).PD-A and PD-NA groups did not differ in age, disease duration, treatment, and motor condition, but differed in recall (p<0.001) and executive tasks (p<0.001). Immediate free recall had the highest predictive value for apathy (F = 10.94; p = 0.002). Depression and apathy had a weak correlation (Pearson index= 0.3; p<0.07), with three items of the depression scale correlating with apathy (Pearson index between .3 and.4; p<0.04). The depressed and non-depressed PD patients within the non-apathetic group did not differ.Apathy, but not depression, is associated with deficit in implementing efficient cognitive strategies. As the implementation of efficient strategies relies on the fronto-striatal circuit, we conclude that apathy, unlike depression, is an early expression of executive impairment in PD

Association of PCSK1 rs6234 with Obesity and Related Traits in a Chinese Han Population

Background: Common variants in PCSK1 have been reported to be associated with obesity in populations of European origin. We aimed to replicate this association in Chinese. Methodology/Principal Findings: Two PCSK1 variants rs6234 and rs6235 (in strong LD with each other, r 2 = 0.98) were genotyped in a population-based cohort of 3,210 Chinese Hans. The rs6234 was used for further association analyses with obesity and related traits. We found no significant association of rs6234 with obesity, overweight, BMI, waist circumference, or body fat percentage (P.0.05) in all participants. However, the rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight (OR 1.21[1.03–1.43], P = 0.0193) and a trend toward association with obesity (OR 1.25[0.98–1.61], P = 0.08) in men, but not in women (P$0.29). Consistently, the rs6234 G-allele showed significant association with increased BMI (P = 0.0043), waist circumference (P = 0.008) and body fat percentage (P = 0.0131) only in men, not in women (P$0.24). Interestingly, the rs6234 G-allele was significantly associated with increased HOMA-B (P = 0.0059) and decreased HOMA-S (P = 0.0349) in all participants. Conclusion/Significance: In this study, we found modest evidence for association of the PCSK1 rs6234 with BMI and overweight in men only but not in women, which suggested that PCSK1 rs6234 might not be an important contributor t

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base