Current CONtrolled Transmit And Receive Coil Elements (C2ONTAR) for Parallel Acquisition and Parallel Excitation Techniques at High-Field MRI

A novel intrinsically decoupled transmit and receive radio-frequency coil element is presented for applications in parallel imaging and parallel excitation techniques in high-field magnetic resonance imaging. Decoupling is achieved by a twofold strategy: during transmission elements are driven by current sources, while during signal reception resonant elements are switched to a high input impedance preamplifier. To avoid B0 distortions by magnetic impurities or DC currents a resonant transmission line is used to relocate electronic components from the vicinity of the imaged object. The performance of a four-element array for 3 T magnetic resonance tomograph is analyzed by means of simulation, measurements of electromagnetic fields and bench experiments. The feasibility of parallel acquisition and parallel excitation is demonstrated and compared to that of a conventional power source-driven array of equivalent geometry. Due to their intrinsic decoupling the current-controlled elements are ideal basic building blocks for multi-element transmit and receive arrays of flexible geometry

Ultrahigh-Field MRI in Human Ischemic Stroke – a 7 Tesla Study

INTRODUCTION: Magnetic resonance imaging (MRI) using field strengths up to 3 Tesla (T) has proven to be a powerful tool for stroke diagnosis. Recently, ultrahigh-field (UHF) MRI at 7 T has shown relevant diagnostic benefits in imaging of neurological diseases, but its value for stroke imaging has not been investigated yet. We present the first evaluation of a clinically feasible stroke imaging protocol at 7 T. For comparison an established stroke imaging protocol was applied at 3 T. METHODS: In a prospective imaging study seven patients with subacute and chronic stroke were included. Imaging at 3 T was immediately followed by 7 T imaging. Both protocols included T1-weighted 3D Magnetization-Prepared Rapid-Acquired Gradient-Echo (3D-MPRAGE), T2-weighted 2D Fluid Attenuated Inversion Recovery (2D-FLAIR), T2-weighted 2D Fluid Attenuated Inversion Recovery (2D-T2-TSE), T2* weighted 2D Fast Low Angle Shot Gradient Echo (2D-HemoFLASH) and 3D Time-of-Flight angiography (3D-TOF). RESULTS: The diagnostic information relevant for clinical stroke imaging obtained at 3 T was equally available at 7 T. Higher spatial resolution at 7 T revealed more anatomical details precisely depicting ischemic lesions and periinfarct alterations. A clear benefit in anatomical resolution was also demonstrated for vessel imaging at 7 T. RF power deposition constraints induced scan time prolongation and reduced brain coverage for 2D-FLAIR, 2D-T2-TSE and 3D-TOF at 7 T versus 3 T. CONCLUSIONS: The potential of 7 T MRI for human stroke imaging is shown. Our pilot study encourages a further evaluation of the diagnostic benefit of stroke imaging at 7 T in a larger study

Analysis of In-Vivo LacR-Mediated Gene Repression Based on the Mechanics of DNA Looping

Interactions of E. coli lac repressor (LacR) with a pair of operator sites on the same DNA molecule can lead to the formation of looped nucleoprotein complexes both in vitro and in vivo. As a major paradigm for loop-mediated gene regulation, parameters such as operator affinity and spacing, repressor concentration, and DNA bending induced by specific or non-specific DNA-binding proteins (e.g., HU), have been examined extensively. However, a complete and rigorous model that integrates all of these aspects in a systematic and quantitative treatment of experimental data has not been available. Applying our recent statistical-mechanical theory for DNA looping, we calculated repression as a function of operator spacing (58–156 bp) from first principles and obtained excellent agreement with independent sets of in-vivo data. The results suggest that a linear extended, as opposed to a closed v-shaped, LacR conformation is the dominant form of the tetramer in vivo. Moreover, loop-mediated repression in wild-type E. coli strains is facilitated by decreased DNA rigidity and high levels of flexibility in the LacR tetramer. In contrast, repression data for strains lacking HU gave a near-normal value of the DNA persistence length. These findings underscore the importance of both protein conformation and elasticity in the formation of small DNA loops widely observed in vivo, and demonstrate the utility of quantitatively analyzing gene regulation based on the mechanics of nucleoprotein complexes

Group differences in physician responses to handheld presentation of clinical evidence: a verbal protocol analysis

<p>Abstract</p> <p>Background</p> <p>To identify individual differences in physicians' needs for the presentation of evidence resources and preferences for mobile devices.</p> <p>Methods</p> <p>Within-groups analysis of responses to semi-structured interviews. Interviews consisted of using prototypes in response to task-based scenarios. The prototypes were implemented on two different form factors: a tablet style PC and a pocketPC. Participants were from three user groups: general internists, family physicians and medicine residents, and from two different settings: urban and semi-urban. Verbal protocol analysis, which consists of coding utterances, was conducted on the transcripts of the testing sessions. Statistical relationships were investigated between staff physicians' and residents' background variables, self-reported experiences with the interfaces, and verbal code frequencies.</p> <p>Results</p> <p>47 physicians were recruited from general internal medicine, family practice clinics and a residency training program. The mean age of participants was 42.6 years. Physician specialty had a greater effect on device and information-presentation preferences than gender, age, setting or previous technical experience. Family physicians preferred the screen size of the tablet computer and were less concerned about its portability. Residents liked the screen size of the tablet, but preferred the portability of the pocketPC. Internists liked the portability of the pocketPC, but saw less advantage to the large screen of the tablet computer (F[2,44] = 4.94, p = .012).</p> <p>Conclusion</p> <p>Different types of physicians have different needs and preferences for evidence-based resources and handheld devices. This study shows how user testing can be incorporated into the process of design to inform group-based customization.</p

Towards standardized measurement of adverse events in spine surgery: conceptual model and pilot evaluation

BACKGROUND: Independent of efficacy, information on safety of surgical procedures is essential for informed choices. We seek to develop standardized methodology for describing the safety of spinal operations and apply these methods to study lumbar surgery. We present a conceptual model for evaluating the safety of spine surgery and describe development of tools to measure principal components of this model: (1) specifying outcome by explicit criteria for adverse event definition, mode of ascertainment, cause, severity, or preventability, and (2) quantitatively measuring predictors such as patient factors, comorbidity, severity of degenerative spine disease, and invasiveness of spine surgery. METHODS: We created operational definitions for 176 adverse occurrences and established multiple mechanisms for reporting them. We developed new methods to quantify the severity of adverse occurrences, degeneration of lumbar spine, and invasiveness of spinal procedures. Using kappa statistics and intra-class correlation coefficients, we assessed agreement for the following: four reviewers independently coding etiology, preventability, and severity for 141 adverse occurrences, two observers coding lumbar spine degenerative changes in 10 selected cases, and two researchers coding invasiveness of surgery for 50 initial cases. RESULTS: During the first six months of prospective surveillance, rigorous daily medical record reviews identified 92.6% of the adverse occurrences we recorded, and voluntary reports by providers identified 38.5% (surgeons reported 18.3%, inpatient rounding team reported 23.1%, and conferences discussed 6.1%). Trained observers had fair agreement in classifying etiology of 141 adverse occurrences into 18 categories (kappa = 0.35), but agreement was substantial (kappa ≥ 0.61) for 4 specific categories: technical error, failure in communication, systems failure, and no error. Preventability assessment had moderate agreement (mean weighted kappa = 0.44). Adverse occurrence severity rating had fair agreement (mean weighted kappa = 0.33) when using a scale based on the JCAHO Sentinel Event Policy, but agreement was substantial for severity ratings on a new 11-point numerical severity scale (ICC = 0.74). There was excellent inter-rater agreement for a lumbar degenerative disease severity score (ICC = 0.98) and an index of surgery invasiveness (ICC = 0.99). CONCLUSION: Composite measures of disease severity and surgery invasiveness may allow development of risk-adjusted predictive models for adverse events in spine surgery. Standard measures of adverse events and risk adjustment may also facilitate post-marketing surveillance of spinal devices, effectiveness research, and quality improvement

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD